Barry Reisberg, M.D.

THE CONCEPT OF RETROGENESIS IN ALZHEIMER'S DISEASE: ETHICAL AND FORENSIC IMPLICATIONS
Borza, Liana Rada; Reisberg, Barry; Chiosa, Anca; Astarastoae, Vasile
2011 JUL-SEP ;9(3):63-72, Revista romana de bioetica = Romanian journal of bioethics
The concept of retrogenesis has been documented by several studies as the process by which degenerative mechanisms in Alzheimer's disease (AD) reverse the order of acquisition in normal human development. The objective of the present study is to offer expert opinion on the possible ethical and forensic implications of retro genesis. In this regard, we constructed a six-item instrument called 'Questionnaire regarding possible ethical and forensic implications of retrogenesis', which we applied to three professional groups that are directly involved in clinical and forensic evaluation of AD persons, namely, psychiatrists, psychologists and forensic pathologists. The majority of experts questioned in this survey considered it ethical to start from the concept of retrogenesis when approaching AD. Moreover, most of the study participants agreed that it would be ethical to use psychometric tests and programs of cognitive stimulation for the child in the patient with AD. It can also be noted that more than half of the professionals involved in our study considered it ethical to apply child abuse evaluation tests to the AD patients. Furthermore, 61.2% of the opinion survey respondents agreed that it would be necessary to use the concept of retrogenesis for assessing mental capacity in these patients. In addition, most professionals surveyed herein pointed out that it would be necessary to enact legislative proposals on the protection of the patient with AD which would be adapted from the model of the current child protection legislation. This study appears to represent the first expert opinion survey that concerns the ethical and forensic implications of the concept of retrogenesis in AD
— id: 141093, year: 2011, vol: 9, page: 63, stat: Journal Article,

A RETROGENIC MODEL FOR DETECTING ABUSE OF INSTITUTIONALIZED PEOPLE WITH ALZHEIMER'S DISEASE
Borza, Liana Rada; Reisberg, Barry; Macarie, George Florian; Astarastoae, Vasile
2011 JAN-MAR ;9(1):65-75, Revista romana de bioetica = Romanian journal of bioethics
Several studies draw attention to the fact that elder abuse is a complex and multi-dimensional social problem. It has been noticed that institutionalization and disturbing behaviors that result from dementia represent risk factors for mistreatment. In this regard, we have tested if an adapted version of Child Abuse and Trauma Scale can efficiently assess different types of abuse on people with Alzheimer's disease (AD) living in institutional settings. Our choice of an instrument that would ordinarily be used to measure abuse in childhood and adolescence is based on the concept of retrogenesis. This term refers to the process of AD degenerative reversal recapitulation of human ontogenic acquisition patterns. In the present study, we have found that the chosen scale is a reliable screening tool for different forms of abuse in institutionalized AD subjects, providing both a useful, ethically and humanely relevant assessment instrument, and additional evidence for the retrogenesis process. With respect to the frequency of occurrence, neglect and emotional abuse were the most common forms of abuse reported by the study participants, followed by punishment and physical abuse, while sexual abuse was the least reported. Women questioned in this study were found to be more predisposed than men to sexual abuse, while the men were found to be more predisposed to physical abuse. Moreover, the subjects with mild AD reported lower levels of punishment, neglect and emotional abuse when compared to the other AD institutional residents included in this study. In conclusion, our findings will hopefully contribute to the more widespread identification of abuse in persons with dementia, as well as to the development of prevention and intervention strategies
— id: 133323, year: 2011, vol: 9, page: 65, stat: Journal Article,

Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease
Naj, Adam C; Jun, Gyungah; Beecham, Gary W; Wang, Li-San; Vardarajan, Badri Narayan; Buros, Jacqueline; Gallins, Paul J; Buxbaum, Joseph D; Jarvik, Gail P; Crane, Paul K; Larson, Eric B; Bird, Thomas D; Boeve, Bradley F; Graff-Radford, Neill R; De Jager, Philip L; Evans, Denis; Schneider, Julie A; Carrasquillo, Minerva M; Ertekin-Taner, Nilufer; Younkin, Steven G; Cruchaga, Carlos; Kauwe, John S K; Nowotny, Petra; Kramer, Patricia; Hardy, John; Huentelman, Matthew J; Myers, Amanda J; Barmada, Michael M; Demirci, F Yesim; Baldwin, Clinton T; Green, Robert C; Rogaeva, Ekaterina; George-Hyslop, Peter St; Arnold, Steven E; Barber, Robert; Beach, Thomas; Bigio, Eileen H; Bowen, James D; Boxer, Adam; Burke, James R; Cairns, Nigel J; Carlson, Chris S; Carney, Regina M; Carroll, Steven L; Chui, Helena C; Clark, David G; Corneveaux, Jason; Cotman, Carl W; Cummings, Jeffrey L; Decarli, Charles; Dekosky, Steven T; Diaz-Arrastia, Ramon; Dick, Malcolm; Dickson, Dennis W; Ellis, William G; Faber, Kelley M; Fallon, Kenneth B; Farlow, Martin R; Ferris, Steven; Frosch, Matthew P; Galasko, Douglas R; Ganguli, Mary; Gearing, Marla; Geschwind, Daniel H; Ghetti, Bernardino; Gilbert, John R; Gilman, Sid; Giordani, Bruno; Glass, Jonathan D; Growdon, John H; Hamilton, Ronald L; Harrell, Lindy E; Head, Elizabeth; Honig, Lawrence S; Hulette, Christine M; Hyman, Bradley T; Jicha, Gregory A; Jin, Lee-Way; Johnson, Nancy; Karlawish, Jason; Karydas, Anna; Kaye, Jeffrey A; Kim, Ronald; Koo, Edward H; Kowall, Neil W; Lah, James J; Levey, Allan I; Lieberman, Andrew P; Lopez, Oscar L; Mack, Wendy J; Marson, Daniel C; Martiniuk, Frank; Mash, Deborah C; Masliah, Eliezer; McCormick, Wayne C; McCurry, Susan M; McDavid, Andrew N; McKee, Ann C; Mesulam, Marsel; Miller, Bruce L; Miller, Carol A; Miller, Joshua W; Parisi, Joseph E; Perl, Daniel P; Peskind, Elaine; Petersen, Ronald C; Poon, Wayne W; Quinn, Joseph F; Rajbhandary, Ruchita A; Raskind, Murray; Reisberg, Barry; Ringman, John M; Roberson, Erik D; Rosenberg, Roger N; Sano, Mary; Schneider, Lon S; Seeley, William; Shelanski, Michael L; Slifer, Michael A; Smith, Charles D; Sonnen, Joshua A; Spina, Salvatore; Stern, Robert A; Tanzi, Rudolph E; Trojanowski, John Q; Troncoso, Juan C; Van Deerlin, Vivianna M; Vinters, Harry V; Vonsattel, Jean Paul; Weintraub, Sandra; Welsh-Bohmer, Kathleen A; Williamson, Jennifer; Woltjer, Randall L; Cantwell, Laura B; Dombroski, Beth A; Beekly, Duane; Lunetta, Kathryn L; Martin, Eden R; Kamboh, M Ilyas; Saykin, Andrew J; Reiman, Eric M; Bennett, David A; Morris, John C; Montine, Thomas J; Goate, Alison M; Blacker, Deborah; Tsuang, Debby W; Hakonarson, Hakon; Kukull, Walter A; Foroud, Tatiana M; Haines, Jonathan L; Mayeux, Richard; Pericak-Vance, Margaret A; Farrer, Lindsay A; Schellenberg, Gerard D
2011 May;43(5):436-441, Nature genetics
The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A (rs4938933; stages 1 and 2, meta-analysis P (P(M)) = 1.7 x 10(-9), joint analysis P (P(J)) = 1.7 x 10(-9); stages 1, 2 and 3, P(M) = 8.2 x 10(-12)), CD2AP (rs9349407; stages 1, 2 and 3, P(M) = 8.6 x 10(-9)), EPHA1 (rs11767557; stages 1, 2 and 3, P(M) = 6.0 x 10(-10)) and CD33 (rs3865444; stages 1, 2 and 3, P(M) = 1.6 x 10(-9)). We also replicated previous associations at CR1 (rs6701713; P(M) = 4.6 x 10(-10), P(J) = 5.2 x 10(-11)), CLU (rs1532278; P(M) = 8.3 x 10(-8), P(J) = 1.9 x 10(-8)), BIN1 (rs7561528; P(M) = 4.0 x 10(-14), P(J) = 5.2 x 10(-14)) and PICALM (rs561655; P(M) = 7.0 x 10(-11), P(J) = 1.0 x 10(-10)), but not at EXOC3L2, to late-onset Alzheimer's disease susceptibility
— id: 134258, year: 2011, vol: 43, page: 436, stat: Journal Article,

Impact of hormone replacement therapy (HRT) usage on 7-year outcome of older persons with subjective cognitive impairment
Reisberg B.; Boksay I.; Osorio R.; Torossian C.; Janisar M.; Lobach I.; Joseph P.; Monteiro I.; Gill T.; Khan A.
2011 ;7(4 SUPPL 1):S97-S97, Alzheimer's & Dementia
Background: Subjective Cognitive Impairment (SCI), Global Deterioration Scale stage 2, is common in older persons. A study of otherwise healthy persons found that 54% of SCI subjects followed over 7 years progressed toMild Cognitive Impairment (MCI) or dementia (Reisberg, et al., Alzheimer's & Dementia, 2010).1 Medications may contribute to SCI occurrence, however, their influence on SCI outcome is largely unknown. Therefore, we investigated the impact of medications subsequently associated with dementia risk in our previously characterized cohort.1 Methods: Subjects with SCI at baseline from our 2010 publication1 were studied. These subjects had baseline evaluations between 1/1/1984 and 12/31/1997 and were followed until 12/31/2001. Medication data was available on 143 of 166 subjects. Subjects receiving topical estrogen at the baseline evaluationwere excluded fromthese analyses. At baseline, evaluable subjects (N = 140; 91 women, 49 men) had a mean age of 66.5 +/- 8.4 years; 15.6 +/- 2.7 years of education; and MMSE scores of 29.0 +/- 1.2. Twenty-two women (24.2%) were receiving HRT, comprising estrogen (n = 10) or estrogen-progesterone combination (n = 12). Results: Subjects were followed over 7.0 +/- 3.4 years. Increased age and education were associated with clinical progression in this cohort (OR = 1.06 and 0.78 respectively; p-values < 0.05). Three of ten estrogenonly (30%) subjects progressed (2 to MCI, 1 to dementia); seven of twelve estrogen-progesterone (58.3%) subjects progressed (6 toMCI, 1 to dementia). In the total HRT group, 45.5% progressed, whereas in the control group (no-HRT), 62 of 118 progressed (52.5%), (49 to MCI, 13 to dementia). Age, education and gender did not differ significantly between subjects in the study groups (t-test and chi-square p-values, NS). Multivariate logistic regression for each condition was performed investigating differences in therapy, age, gender and education. Therapy was not associated with progression status. Conclusions: HRT did not influence 7-year outcome in SCI subjects. Therefore, SCI subjects were not particularly sensitive to reported deleterious effects of HRT on progression of cognitive decline. Systematic longitudinal investigation of possible effects of other medications/conditions on progression of SCI to MCI/dementia is required to identify substances that may regulate/prevent this process
— id: 136972, year: 2011, vol: 7, page: S97, stat: Journal Article,

The fast: A brief, practical, comprehensive, valid functional assessment for alzheimer's disease staging, diagnosis and differential diagnosis in the primary care setting
Reisberg B.; Wegiel J.; Franssen E.; Monteiro I.; Torossian C.; Anwar S.; Gill T.; Boksay I.; Auer S.; Shimada M.; Meguro K.
2011 ;7(4 SUPPL 1):S82-S82, Alzheimer's & Dementia
Background: Impairment in functional capacities is an integral domain in AD presentation, diagnosis and progression. Among many functional scales for AD assessment, the Functional Assessment Staging scale (FAST) (Table 1) uniquely: (1) charts the entire course of AD, from normal aging to most severe AD; (2) has relevance for AD diagnosis and differential diagnosis; and (3) is brief and easy to utilize. Methods: Reliability, validity, and utility of the FAST have been documented in worldwide studies and clinical settings. Results: The FAST has excellent reliability (e.g., Foster et al., Int J Geriatr. Psychiatry,1988; Sclan and Reisberg, Int. Psychogeriatr., 1992). Concurrent validity has been demonstrated with: cognitive assessments across the severity spectrum (e.g., Reisberg, et al., Int. Psychogeriatr., 1992; Shimada, et al., Psychogeriatrics, 2003; Auer et al., JAGS, 1994); other dementia scales (Na et al., JAD, 2010); and neurologic assessments (Franssen and Reisberg, Int. Psychogeriatr., 1997). Criterion validity investigations have indicated superiority of the FAST in comparison with the MMSE, in tracking the course of AD. E.g., in a 5 year prospective longitudinal study of AD course, the FAST accounted for w 2x the temporal variance of the MMSE (Reisberg, et al., Int. Psychogeriatr., 1996). Also, in a range where the MMSE is zero, the FAST demonstrated very robust relationships to AD neuropathology (e.g., r = 0.9 [p 0.01], with hippocampal cornu ammonis neuronal loss), (Bobinski, et al., J. Neuropathol. Exp. Neurol., 1997). Additionally, in a pivotal trial, associated with worldwide approvals of memantine for AD treatment, FAST scores were sensitive to the intervention, MMSE change was not (Reisberg, et al., N Engl J Med., 2003). The FAST has shown widespread utility (e.g., usage mandated by U.S.A. Medicare since 1998, and the U.S.A. Veterans Administration System, since 2008). Conclusions: As noted in a Korean publication, the FAST is a rapid and easy to use staging tool with excellent validity. it. successfully measure[ s] detailed function throughout the entire course of AD. the FAST is composed of simple . and easy to understand sentences
— id: 136973, year: 2011, vol: 7, page: S82, stat: Journal Article,

Methodologies for Clinical Trials in Pre-MCI Persons with Subjective Cognitive Impairment
Reisberg, B; Shulman, MB; Osorio, RS; Kumar, P; Gill, TJ; Janisar, M; Lobach, I
26th International Conference of Alzheimer's Disease International Bologna : MEDIMOND s.r.l., 2011,
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Alzheimer's disease
Reisberg, Barry; et al
Medical aspects of disability : a handbook for the rehabilitation professional New York : Springer, c2011,
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Clinical Assessment Methodology for Alzheimer's Disease Prevention Trials: A Global and Multi-Axial 2 Year Study of Pre-Mild Cognitive Impairment (Pre-MCI) Subjective Cognitive Impairment (SCI)
Reisberg, Barry; Osorio, Ricardo; Khan, Asif; Roy, Kamalika; Torossian, Carol; Monteiro, Isabel; Anwar, Salman; Shulman, Melanie B; Lobach, Iryna
2011 ;36:?-? #70, Neuropsychopharmacology
— id: 147669, year: 2011, vol: 36, page: ?, stat: Journal Article,

Link between DYRK1A overexpression and several-fold enhancement of neurofibrillary degeneration with 3-repeat tau protein in Down syndrome
Wegiel, Jerzy; Kaczmarski, Wojciech; Barua, Madhabi; Kuchna, Izabela; Nowicki, Krzysztof; Wang, Kuo-Chiang; Wegiel, Jarek; Yang, Shuang Ma; Frackowiak, Janusz; Mazur-Kolecka, Bozena; Silverman, Wayne P; Reisberg, Barry; Monteiro, Isabel; de Leon, Mony; Wisniewski, Thomas; Dalton, Arthur; Lai, Florence; Hwang, Yu-Wen; Adayev, Tatyana; Liu, Fei; Iqbal, Khalid; Iqbal, Inge-Grundke; Gong, Cheng-Xin
2011 Jan;70(1):36-50, Journal of neuropathology & experimental neurology
Triplication of chromosome 21 in Down syndrome (DS) results in overexpression of the minibrain kinase/dual-specificity tyrosine phosphorylated and regulated kinase 1A gene (DYRK1A). DYRK1A phosphorylates cytoplasmic tau protein and appears in intraneuronal neurofibrillary tangles (NFTs). We have previously shown significantly more DYRK1A-positive NFTs in DS brains than in sporadic Alzheimer disease (AD) brains. This study demonstrates a gene dosage-proportional increase in the level of DYRK1A in DS in the cytoplasm and the cell nucleus, and enhanced cytoplasmic and nuclear immunoreactivity of DYRK1A in DS. The results suggest that overexpressed DYRK1A may alter both phosphorylation of tau and alternative splicing factor (ASF). Two-dimensional electrophoresis revealed modification of ASF phosphorylation in DS/AD and AD in comparison to controls. Altered phosphorylation of ASF by overexpressed nuclear DYRK1A may contribute to the alternative splicing of the tau gene and an increase by 2.68 x of the 3R/4R ratio in DS/AD, and a several-fold increase in the number of 3R tau-positive NFTs in DS/AD subjects compared with that in sporadic AD subjects. These data support the hypothesis that phosphorylation of ASF by overexpressed DYRK1A may contribute to alternative splicing of exon 10, increased expression of 3R tau, and early onset of neurofibrillary degeneration in DS
— id: 134289, year: 2011, vol: 70, page: 36, stat: Journal Article,

Nonpharmacological therapies in Alzheimer's disease: a systematic review of efficacy
Olazaran, Javier; Reisberg, Barry; Clare, Linda; Cruz, Isabel; Pena-Casanova, Jordi; Del Ser, Teodoro; Woods, Bob; Beck, Cornelia; Auer, Stefanie; Lai, Claudia; Spector, Aimee; Fazio, Sam; Bond, John; Kivipelto, Miia; Brodaty, Henry; Rojo, Jose Manuel; Collins, Helen; Teri, Linda; Mittelman, Mary; Orrell, Martin; Feldman, Howard H; Muniz, Ruben
2010 ;30(2):161-178, Dementia geriatric & cognitive disorders
INTRODUCTION: Nonpharmacological therapies (NPTs) can improve the quality of life (QoL) of people with Alzheimer's disease (AD) and their carers. The objective of this study was to evaluate the best evidence on the effects of NPTs in AD and related disorders (ADRD) by performing a systematic review and meta-analysis of the entire field. METHODS: Existing reviews and major electronic databases were searched for randomized controlled trials (RCTs). The deadline for study inclusion was September 15, 2008. Intervention categories and outcome domains were predefined by consensus. Two researchers working together detected 1,313 candidate studies of which 179 RCTs belonging to 26 intervention categories were selected. Cognitive deterioration had to be documented in all participants, and degenerative etiology (indicating dementia) had to be present or presumed in at least 80% of the subjects. Evidence tables, meta-analysis and summaries of results were elaborated by the first author and reviewed by author subgroups. Methods for rating level of evidence and grading practice recommendations were adapted from the Oxford Center for Evidence-Based Medicine. RESULTS: Grade A treatment recommendation was achieved for institutionalization delay (multicomponent interventions for the caregiver, CG). Grade B recommendation was reached for the person with dementia (PWD) for: improvement in cognition (cognitive training, cognitive stimulation, multicomponent interventions for the PWD); activities of daily living (ADL) (ADL training, multicomponent interventions for the PWD); behavior (cognitive stimulation, multicomponent interventions for the PWD, behavioral interventions, professional CG training); mood (multicomponent interventions for the PWD); QoL (multicomponent interventions for PWD and CG) and restraint prevention (professional CG training); for the CG, grade B was also reached for: CG mood (CG education, CG support, multicomponent interventions for the CG); CG psychological well-being (cognitive stimulation, multicomponent interventions for the CG); CG QoL (multicomponent interventions for PWD and CG). CONCLUSION: NPTs emerge as a useful, versatile and potentially cost-effective approach to improve outcomes and QoL in ADRD for both the PWD and CG
— id: 138218, year: 2010, vol: 30, page: 161, stat: Journal Article,

Outcome over seven years of healthy adults with and without subjective cognitive impairment
Reisberg, Barry; Shulman, Melanie B; Torossian, Carol; Leng, Ling; Zhu, Wei
2010 Jan;6(1):11-24, Alzheimer's & Dementia
BACKGROUND: Subjective cognitive impairment (SCI) in older persons without manifest symptomatology is a common condition with a largely unclear prognosis. We hypothesized that (1) examining outcome for a sufficient period by using conversion to mild cognitive impairment (MCI) or dementia would clarify SCI prognosis, and (2) with the aforementioned procedures, the prognosis of SCI subjects would differ significantly from that of demographically matched healthy subjects, free of SCI, termed no cognitive impairment (NCI) subjects. METHODS: A consecutive series of healthy subjects, aged > or =40 years, presenting with NCI or SCI to a brain aging and dementia research center during a 14-year interval, were studied and followed up during an 18-year observation window. The study population (60 NCI, 200 SCI, 60% female) had a mean age of 67.2 +/- 9.1 years, was well-educated (mean, 15.5 +/- 2.7 years), and cognitively normal (Mini-Mental State Examination, 29.1 +/- 1.2). RESULTS: A total of 213 subjects (81.9% of the study population) were followed up. Follow-up occurred during a mean period of 6.8 +/- 3.4 years, and subjects had a mean of 2.9 +/- 1.6 follow-up visits. Seven NCI (14.9%) and 90 SCI (54.2%) subjects declined (P < .0001). Of NCI decliners, five declined to MCI and two to probable Alzheimer's disease. Of SCI decliners, 71 declined to MCI and 19 to dementia diagnoses. Controlling for baseline demographic variables and follow-up time, Weibull proportional hazards model revealed increased decline in SCI subjects (hazard ratio, 4.5; 95% confidence interval, 1.9-10.3), whereas the accelerated failure time model analysis with an underlying Weibull survival function showed that SCI subjects declined more rapidly, at 60% of the rate of NCI subjects (95% confidence interval, 0.45-0.80). Furthermore, mean time to decline was 3.5 years longer for NCI than for SCI subjects (P = .0003). CONCLUSIONS: These results indicate that SCI in subjects with normal cognition is a harbinger of further decline in most subjects during a 7-year mean follow-up interval. Relevance for community populations should be investigated, and prevention studies in this at-risk population should be explored
— id: 107277, year: 2010, vol: 6, page: 11, stat: Journal Article,

Functional, Global and Cognitive Decline Correlates to Accumulation of Alzheimer's Pathology in MCI and AD
Sabbagh, MN; Cooper, K; DeLange, J; Stoehr, JD; Thind, K; Lahti, T; Reisberg, B; Sue, L; Vedders, L; Fleming, SR; Beach, TG
2010 JUN ;7(4):280-286, Current Alzheimer research
Background: Cognitive, global and functional instruments have been extensively investigated for correlations with neuropathological changes such as neurofibrillary tangles (NFTs), plaques, and synapse loss in the brain. Objective: Our objective is to correlate the functional, global and cognitive decline assessed clinically with the neuropathological changes observed in a large prospectively characterized cohort of mild cognitive impairment (MCI) and Alzheimer's disease (AD). Methods: We examined 150 subjects (16 MCI and 134 AD) that were prospectively assessed and longitudinally followed to autopsy. MCI subjects clinically met Petersen criteria for single or multi-domain amnestic MCI. AD subjects clinically met NINCDS-ADRDA criteria for probable or possible AD. All subjects received the Functional Assessment Staging (FAST), the Global Deterioration Scale (GDS), and the Mini Mental State Examination (MMSE) ante-mortem. Plaque and tangle counts were gathered for hippocampus, entorhinal cortex, frontal, temporal and parietal cortices. Braak staging was performed as well. Results: The GDS, FAST and MMSE correlated with plaque counts in all regions. The GDS, FAST and MMSE correlated with tangle counts in in all regions. The three instruments also correlated with the Braak score. The MMSE and GDS correlate better than the FAST in most regions. Conclusions: Accumulation of neuropathology appears to correlate with functional, global, and cognitive decline as people progress from MCI through AD. In our study, both tangle and plaque accumulation correlated to clinical decline but when AD is considered alone, the correlations are not as robust
— id: 109688, year: 2010, vol: 7, page: 280, stat: Journal Article,

A roadmap for the prevention of dementia II: Leon Thal Symposium 2008
Khachaturian, Zaven S; Snyder, Peter J; Doody, Rachelle; Aisen, Paul; Comer, Meryl; Dwyer, John; Frank, Richard A; Holzapfel, Andrew; Khachaturian, Ara S; Korczyn, Amos D; Roses, Allen; Simpkins, James W; Schneider, Lon S; Albert, Marilyn S; Egge, Robert; Deves, Aaron; Ferris, Steven; Greenberg, Barry D; Johnson, Carl; Kukull, Walter A; Poirier, Judes; Schenk, Dale; Thies, William; Gauthier, Serge; Gilman, Sid; Bernick, Charles; Cummings, Jeffrey L; Fillit, Howard; Grundman, Michael; Kaye, Jeff; Mucke, Lennart; Reisberg, Barry; Sano, Mary; Pickeral, Oxana; Petersen, Ronald C; Mohs, Richard C; Carrillo, Maria; Corey-Bloom, Jody P; Foster, Norman L; Jacobsen, Steve; Lee, Virginia; Potter, William Z; Sabbagh, Marwan N; Salmon, David; Trojanowski, John Q; Wexler, Nancy; Bain, Lisa J
2009 Mar;5(2):85-92, Alzheimer's & Dementia
This document proposes an array of recommendations for a National Plan of Action to accelerate the discovery and development of therapies to delay or prevent the onset of disabling symptoms of Alzheimer's disease. A number of key scientific and public-policy needs identified in this document will be incorporated by the Alzheimer Study Group into a broader National Alzheimer's Strategic Plan, which will be presented to the 111th Congress and the Obama administration in March 2009. The Alzheimer's Strategic Plan is expected to include additional recommendations for governance, family support, healthcare, and delivery of social services
— id: 101829, year: 2009, vol: 5, page: 85, stat: Journal Article,

FDG-PET changes in brain glucose metabolism from normal cognition to pathologically verified Alzheimer's disease
Mosconi, Lisa; Mistur, Rachel; Switalski, Remigiusz; Tsui, Wai Hon; Glodzik, Lidia; Li, Yi; Pirraglia, Elizabeth; De Santi, Susan; Reisberg, Barry; Wisniewski, Thomas; de Leon, Mony J
2009 May;36(5):811-822, European journal of nuclear medicine & molecular imaging
PURPOSE: We report the first clinicopathological series of longitudinal FDG-PET scans in post-mortem (PM) verified cognitively normal elderly (NL) followed to the onset of Alzheimer's-type dementia (DAT), and in patients with mild DAT with progressive cognitive deterioration. METHODS: Four NL subjects and three patients with mild DAT received longitudinal clinical, neuropsychological and dynamic FDG-PET examinations with arterial input functions. NL subjects were followed for 13 +/- 5 years, received FDG-PET examinations over 7 +/- 2 years, and autopsy 6 +/- 3 years after the last FDG-PET. Two NL declined to mild cognitive impairment (MCI), and two developed probable DAT before death. DAT patients were followed for 9 +/- 3 years, received FDG-PET examinations over 3 +/- 2 years, and autopsy 7 +/- 1 years after the last FDG-PET. Two DAT patients progressed to moderate-to-severe dementia and one developed vascular dementia. RESULTS: The two NL subjects who declined to DAT received a PM diagnosis of definite AD. Their FDG-PET scans indicated a progression of deficits in the cerebral metabolic rate for glucose (CMRglc) from the hippocampus to the parietotemporal and posterior cingulate cortices. One DAT patient showed AD with diffuse Lewy body disease (LBD) at PM, and her last in vivo PET was indicative of possible LBD for the presence of occipital as well as parietotemporal hypometabolism. CONCLUSION: Progressive CMRglc reductions on FDG-PET occur years in advance of clinical DAT symptoms in patients with pathologically verified disease. The FDG-PET profiles in life were consistent with the PM diagnosis
— id: 91500, year: 2009, vol: 36, page: 811, stat: Journal Article,

Commentary on "a roadmap for the prevention of dementia II: Leon Thal Symposium 2008." Subjective cognitive impairment as an antecedent of Alzheimer's dementia: policy import
Reisberg, Barry; Shulman, Melanie B
2009 Mar;5(2):154-156, Alzheimer's & Dementia
— id: 100593, year: 2009, vol: 5, page: 154, stat: Journal Article,

Characteristics and Performance of a Modified Version of the ADCS-CGIC CIBIC plus for Mild Cognitive Impairment Clinical Trials
Schneider, LS; Raman, R; Schmitt, FA; Doody, RS; Insel, P; Clark, CM; Morris, JC; Reisberg, B; Petersen, RC; Ferris, SH
2009 JUL-SEP ;23(3):260-267, Alzheimer disease & associated disorders
Introduction: The Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) was modified for use in mild cognitive impairment (MCI) trials and tested in the ADCS MCI randomized clinical trial of donepezil, vitamin E, and placebo. We assessed feasibility for its use by determining whether or not: (1) it distinguished a medication effect at 6 months and 12 months, (2) baseline demographic or clinical characteristics predicted change, (3) there was an association between MCI-CGIC and change in other clinical measures in order to evaluate external or concurrent validity. Methods: We used a generalized estimating equations approach for ordinal outcome data to test the effects of treatment, baseline characteristics, and change in clinical measures on the MCI-CGIC over 12 months, and ordinal logistic regression to assess the association between MCI-CGIC and change in clinical measures at 6 months and 12 months. Results: On the MCI-CGIC overall, 12.9% and 10.6% were rated as having improved, and 31.6%, and 39.8% as having worsened over 6 months and 12 months, respectively. The MCI-CGIC did not distinguish the donepezil or vitamin E groups from placebo at 6 and 12 months treatment. Variables at screening or baseline that were associated with worse CGIC scores over 6 and 12 months included white race, greater years of education, worse depression, dementia severity rating, cognitive, and daily activities scores, and lower memory domain scores on a neuropsychological battery. Rate of worsening on the MCI-CGIC over 12 months was associated with change on the Alzheimer Disease Assessment Scale-cognitive and on executive function. Worsening at 6 months and 12 months, separately, were associated with the corresponding change in Alzheimer Disease Assessment Scale-cognitive, Activities of Daily Living, Beck Depression Inventory, Mini-Mental State Examination, Clinical Dementia Rating sum of boxes, memory, and executive function. Conclusions: Change detected by the MCI-CGIC was associated with baseline clinical severity and with change in clinical ratings over 6 and 12 months, supporting the validity of a CGIC approach in MCI. The effect size of the donepezil-placebo difference was similar to that of other outcomes at 12 months. About 40% of MCI patients were judged worse and about 11% improved, consistent with clinical experience and other ratings
— id: 102958, year: 2009, vol: 23, page: 260, stat: Journal Article,

An entorhinal cortex sulcal pattern is associated with Alzheimer's disease
Zhan, Jiong; Brys, Miroslaw; Glodzik, Lidia; Tsui, Wai; Javier, Elizabeth; Wegiel, Jerzy; Kuchna, Izabela; Pirraglia, Elizabeth; Li, Yi; Mosconi, Lisa; Saint Louis, Leslie A; Switalski, Remigiusz; De Santi, Susan; Kim, Byeong C; Wisniewski, Thomas; Reisberg, Barry; Bobinski, Matthew; de Leon, Mony J
2009 Mar;30(3):874-882, Human brain mapping
OBJECTIVES:: Magnetic resonance (MRI) studies rely on sulcal boundaries to delineate the human entorhinal cortex (EC) and typically show that EC size is reduced in Alzheimer's disease (AD) and a predictor of future dementia. However, it is unknown if variations in the EC sulcal patterns are associated with AD. We classified the lateral EC sulcal boundary as either a rhinal or collateral pattern and tested the hypotheses that the rhinal pattern was (1) more common in AD and (2) associated with a smaller EC size. EXPERIMENTAL DESIGN:: MRI was used to determine the prevalence of the rhinal and collateral EC patterns in 421 subjects (212 AD, 107 old normal (ONL), and 102 young NL (YNL). Anatomical validation studies of normal subjects were conducted at postmortem in 34 brain hemispheres and in vivo with 21 MRI volume studies. EC pattern reliability was studied with MRI in both cross-sectional and longitudinal designs. PRINCIPAL OBSERVATIONS:: The rhinal pattern was more frequent in the right hemisphere in AD (47%) compared with ONL (28%, odds ratio = 2.25, P = 0.001). EC pattern was not related to ApoE genotype. The validations showed that the EC sulcal pattern was not associated with the neuronal number, surface area, or volume of the EC. In patients with antemortem MRI studied at postmortem it was equivalently determined, that EC patterns are reliably determined on MRI and do not change with the progressive atrophy of AD. CONCLUSIONS:: The data indicate that the right hemisphere rhinal pattern is over represented in AD as compared with control. However, in normal subjects the EC rhinal pattern is not associated with a diminished EC tissue size. It remains to be demonstrated if the right EC rhinal sulcus pattern association with AD reflects genetic or developmental influences. Hum Brain Mapp, 2008. (c) 2008 Wiley-Liss, Inc
— id: 76758, year: 2009, vol: 30, page: 874, stat: Journal Article,

Co morbid diseases enhance the loss of cognition in the elderly
Danji, K; Boksay, I; Boksay, E; Torossian, C; Reisberg, B
2008 APR ;56(4):S104-S105, Journal of the American Geriatrics Society
— id: 78725, year: 2008, vol: 56, page: S104, stat: Journal Article,

Robust and conventional neuropsychological norms: diagnosis and prediction of age-related cognitive decline
De Santi, Susan; Pirraglia, Elizabeth; Barr, William; Babb, James; Williams, Schantel; Rogers, Kimberley; Glodzik, Lidia; Brys, Miroslaw; Mosconi, Lisa; Reisberg, Barry; Ferris, Steven; de Leon, Mony J
2008 Jul;22(4):469-484, Neuropsychology
The aim of the study was to compare the performance of Robust and Conventional neuropsychological norms in predicting clinical decline among healthy adults and in mild cognitive impairment (MCI). The authors developed Robust baseline cross sectional and longitudinal change norms from 113 healthy participants retaining a normal diagnosis for at least 4 years. Baseline Conventional norms were separately created for 256 similar healthy participants without follow-up. Conventional and Robust norms were tested in an independent cohort of longitudinally studied healthy (n=223), MCI (n=136), and Alzheimer's disease (AD, n=162) participants; 84 healthy participants declined to MCI or AD (NL-->DEC), and 44 MCI declined to AD (MCI-->AD). Compared to Conventional norms, baseline Robust norms correctly identified a higher proportion of NL-->DEC with impairment in delayed memory and attention-language domains. Both norms predicted decline from MCI-->AD. Change norms for delayed memory and attention-language significantly incremented baseline classification accuracies. These findings indicate that Robust norms improve identification of healthy individuals who will decline and may be useful for selecting at-risk participants for research studies and early interventions
— id: 86549, year: 2008, vol: 22, page: 469, stat: Journal Article,

A roadmap for the prevention of dementia: the inaugural Leon Thal Symposium
Khachaturian, Zaven S; Petersen, Ronald C; Gauthier, Serge; Buckholtz, Neil; Corey-Bloom, Jodey P; Evans, Bill; Fillit, Howard; Foster, Norman; Greenberg, Barry; Grundman, Michael; Sano, Mary; Simpkins, James; Schneider, Lon S; Weiner, Michael W; Galasko, Doug; Hyman, Bradley; Kuller, Lew; Schenk, Dale; Snyder, Stephen; Thomas, Ronald G; Tuszynski, Mark H; Vellas, Bruno; Wurtman, Richard J; Snyder, Peter J; Frank, Richard A; Albert, Marilyn; Doody, Rachelle; Ferris, Steven; Kaye, Jeffrey; Koo, Edward; Morrison-Bogorad, Marcelle; Reisberg, Barry; Salmon, David P; Gilman, Sid; Mohs, Richard; Aisen, Paul S; Breitner, John C S; Cummings, Jeffrey L; Kawas, Claudia; Phelps, Creighton; Poirier, Judes; Sabbagh, Marwan; Touchon, Jacques; Khachaturian, Ara S; Bain, Lisa J
2008 May;4(3):156-163, Alzheimer's & Dementia
— id: 94416, year: 2008, vol: 4, page: 156, stat: Journal Article,

Mild cognitive impairment (MCI): a historical perspective
Reisberg, Barry; Ferris, Steven H; Kluger, Alan; Franssen, Emile; Wegiel, Jerzy; de Leon, Mony J
2008 Feb;20(1):18-31, International psychogeriatrics
Descriptions of dementia can be traced to antiquity. Prichard (1837) described four dementia stages and Kral (1962) described a 'benign senescent forgetfulness' condition. The American Psychiatric Association's DSM-III (1980) identified an early dementia stage.In 1982, the Clinical Dementia Rating (CDR) and the Global Deterioration Scale (GDS) were published, which identified dementia antecedents. The CDR 0.5 'questionable dementia' stage encompasses both mild dementia and earlier antecedents. GDS stage 3 described a predementia condition termed 'mild cognitive decline' or, alternatively, beginning in 1988, 'mild cognitive impairment' (MCI). This GDS stage 3 MCI condition is differentiated from both a preceding GDS stage 2, 'subjective cognitive impairment' (SCI) stage and a subsequent GDS 4 stage of mild dementia.GDS stage 3 MCI has been well characterized. For example, specific clinical concomitants, mental status and psychological assessment score ranges, behavioral and emotional changes, neuroimaging concomitants, neurological reflex changes, electrophysiological changes, motor and coordination changes, and changes in activities, accompanying GDS stage 3 MCI have been described.Petersen and associates proposed a definition of MCI in 2001 which has been widely used (hereafter referred to as 'Petersen's MCI'). Important differences between GDS stage 3 MCI and Petersen's MCI are that, because of denial, GDS stage 3 MCI does not require memory complaints. Also, GDS stage 3 MCI recognizes the occurrence of executive level functional deficits, which Petersen's MCI did not. Nevertheless, longitudinal and other studies indicate essential compatibility between GDS stage 3 MCI and Petersen's MCI duration and outcomes
— id: 78351, year: 2008, vol: 20, page: 18, stat: Journal Article,

Current evidence for subjective cognitive impairment (SCI) as the pre-mild cognitive impairment (MCI) stage of subsequently manifest Alzheimer's disease
Reisberg, Barry; Gauthier, Serge
2008 Feb;20(1):1-16, International psychogeriatrics
— id: 94417, year: 2008, vol: 20, page: 1, stat: Journal Article,

The pre-mild cognitive impairment, subjective cognitive impairment stage of Alzheimer's disease
Reisberg, Barry; Prichep, Leslie; Mosconi, Lisa; John, E Roy; Glodzik-Sobanska, Lidia; Boksay, Istvan; Monteiro, Isabel; Torossian, Carol; Vedvyas, Alok; Ashraf, Nauman; Jamil, Imran A; de Leon, Mony J
2008 Jan;4(1 Suppl 1):S98-S108, Alzheimer's & Dementia
BACKGROUND: Subjective cognitive impairment (SCI) has been a common, but poorly understood condition, frequently occurring in older persons. METHODS: The past and the emerging literature on SCI and synonymously named conditions is reviewed. RESULTS: Findings include: (1) There is support from at least one longitudinal study for a long-standing concept of SCI as a pre-mild cognitive impairment (MCI) condition lasting approximately 15years. (2) There are complex relationships between SCI and depression and anxiety. (3) Differences in SCI subjects from age-matched non-SCI persons are being published in terms of cognitive tests, hippocampal gray matter density, hippocampal volumes, cerebral metabolism, and urinary cortisol levels. Psychometric and dementia test score differences between SCI and MCI subjects have long been evident. (4) Predictive electrophysiologic features of subsequent decline in SCI subjects are being published. CONCLUSIONS: Studies of therapeutic agents in SCI treatment and resultant Alzheimer's disease prevention appear to be feasible. These trials are also necessary from a public health perspective
— id: 81577, year: 2008, vol: 4, page: S98, stat: Journal Article,

The role of overexpressed DYRK1A protein in the early onset of neurofibrillary degeneration in Down syndrome
Wegiel, Jerzy; Dowjat, Karol; Kaczmarski, Wojciech; Kuchna, Izabela; Nowicki, Krzysztof; Frackowiak, Janusz; Mazur Kolecka, Bozena; Wegiel, Jarek; Silverman, Wayne P; Reisberg, Barry; Deleon, Mony; Wisniewski, Thomas; Gong, Cheng-Xin; Liu, Fei; Adayev, Tatyana; Chen-Hwang, Mo-Chou; Hwang, Yu-Wen
2008 Oct;116(4):391-407, Acta neuropathologica
The gene encoding the minibrain kinase/dual-specificity tyrosine phosphorylated and regulated kinase 1A (DYRK1A) is located in the Down syndrome (DS) critical region of chromosome 21. The third copy of DYRK1A is believed to contribute to abnormal brain development in patients with DS. In vitro studies showing that DYRK1A phosphorylates tau protein suggest that this kinase is also involved in tau protein phosphorylation in the human brain and contributes to neurofibrillary degeneration, and that this contribution might be enhanced in patients with DS. To explore this hypothesis, the brain tissue from 57 subjects including 16 control subjects, 21 patients with DS, and 20 patients with sporadic Alzheimer's disease (AD) was examined with two antibodies to the amino-terminus of DYRK1A (7F3 and G-19), as well as two polyclonal antibodies to its carboxy-terminus (X1079 and 324446). Western blots demonstrated higher levels of full-length DYRK1A in the brains of patients with DS when compared to control brains. Immunocytochemistry revealed that DYRK1A accumulates in neurofibrillary tangles (NFTs) in subjects with sporadic AD and in subjects with DS/AD. Overexpression of DYRK1A in patients with DS was associated with an increase in DYRK1A-positive NFTs in a gene dosage-dependent manner. Results support the hypothesis that overexpressed DYRK1A contributes to neurofibrillary degeneration in DS more significantly than in subjects with two copies of the DYRK1A gene and sporadic AD. Immunoreactivity with antibodies against DYRK1A not only in NFTs but also in granules in granulovacuolar degeneration and in corpora amylacea suggests that DYRK1A is involved in all three forms of degeneration and that overexpression of this kinase may contribute to the early onset of these pathologies in DS
— id: 80400, year: 2008, vol: 116, page: 391, stat: Journal Article,

Subjective memory complaints: presence, severity and future outcome in normal older subjects
Glodzik-Sobanska, Lidia; Reisberg, Barry; De Santi, Susan; Babb, James S; Pirraglia, Elizabeth; Rich, Kenneth E; Brys, Miroslaw; de Leon, Mony J
2007 ;24(3):177-184, Dementia geriatric & cognitive disorders
Background/Aims: Subjective memory complaint (SMC) in normal individuals may predict future cognitive decline. The goal of this study was to examine whether the probability of decline increases with growing intensity of complaint. Methods: Normal subjects over the age of 50 years were included in a longitudinal retrospective study (mean follow-up time = 8 years). All subjects (n = 230) underwent cognitive and medical examination at baseline. The presence of SMC was determined based on Global Deterioration Scale staging. A subgroup of 83 participants also received baseline assessment for the intensity of SMC. Logistic regression was used to predict outcome from baseline variables. Three outcome groups were established at the final visit: nondeclining, declining and diagnostically unstable (i.e. the diagnosis changed over time: from normal to mild cognitive impairment, then back to normal). Results: The presence of SMC was a predictor of future decline but also increased the likelihood of the unstable diagnosis. Increasing intensity of SMC did not further raise the risk for decline. High intensity of complaints and more pronounced affective symptoms predicted the unstable clinical diagnosis. Conclusions: The presence of SMC contributes to the risk of future decline, however, the increasing intensity of the perceived impairment does not further enhance the risk.
— id: 73937, year: 2007, vol: 24, page: 177, stat: Journal Article,

Global measures: utility in defining and measuring treatment response in dementia
Reisberg, Barry
2007 Jun;19(3):421-456, International psychogeriatrics
Global measures used in treatment trials in dementia encompass two distinct categories: (1) clinician's interview-based global severity scales, and (2) clinician's interview-based global change scales. The global severity scales that have been used include: the Clinical Dementia Rating (CDR) and the related CDR-sum of boxes (CDR-SB), the Global Deterioration Scale (GDS), and the Functional Assessment Staging (FAST) procedure. The global severity scales are clearly useful in subject categorization in treatment trials, in part because they are relatively free of many of the sociocultural biases inherent in mental status and psychometric descriptors. Global severity scales can also be used to demonstrate therapeutic efficacy in terms of the general progression of the dementia process. These measures have also proven to be useful in sensitively assessing pharmacotherapeutic effects in Alzheimer's disease (AD) treatment trials. For example, in pivotal trials: (1) in Mild to Moderate AD, the GDS has shown significant change in response to medication, whereas the results on the Mini-mental State Examination (MMSE) were not significant, and (2) in Moderate to Severe AD, the FAST has shown significant pharmacotherapeutic efficacy, whereas the results using the MMSE were not significant. The global change scales employed in dementia trials differ widely in assessment methodology. Clinical Global Impressions of Change (CGIC) scales do not have defined methodologies, whereas Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus) scales are much more elaborate. The CIBIC-Plus procedures require an independent clinician assessment and can provide independent, comprehensive evidence of therapeutic efficacy. The CIBIC-Plus procedure may also be useful in sensitively assessing efficacy in future prevention trials, for example in subjects with Subjective Cognitive Impairment. For Mild Cognitive Impairment (MCI), global severity scales already appear to be one modality for the sensitive assessment of change. The CIBIC-Plus procedures might also productively be applied in future MCI therapeutic trials
— id: 73700, year: 2007, vol: 19, page: 421, stat: Journal Article,

Diagnostic criteria in dementia: A comparison of current criteria, research challenges, and implications for DSM-V and ICD-11
Reisberg, Barry; Sartorius, Norman
Diagnostic issues in dementia: Advancing the research agenda for DSM-V Washington, DC, US: American Psychiatric Association, 2007,
This reprinted article originally appeared in Journal of Geriatric Psychiatry and Neurology, 2006, Vol 19 (3), 137-146. (The following abstract of the original article appeared in record 2006-10281-004.) Planning is being initiated for the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders 5th ed. (DSM-V). Therefore, the dementia diagnosis criteria in the American Psychiatric Association's DSM-IV-TR (4th ed, text revision, 2000) have been compared with the World Health Organization's International Classification of Diseases (10th revision, 1992). Critiques are based primarily on (a) internal consistency and validity of the classification, (b) historical development of the field, YYYconclusions of consensus conferences, and (d) current knowledge and practice. It is suggested that (1) the entire category be labeled 'cognitive disorders,' to better characterize this group of disorders, (2) there is no longer any scientific basis for the presenile versus senile dementia dichotomy at age 65, (3) Alzheimer's disease no longer should have unique status as a 'diagnosis of exclusion,' (4) future manuals should incorporate knowledge regarding the clinical manifestation and course of Alzheimer's disease and other dementias, and (5) the classification 'Pick's disease' should be broadened to 'frontotemporal dementias.' DSM-V should incorporate continuing advances in the neuroscience knowledge base and understanding of these disorders.
— id: 4452, year: 2007, vol: , page: 27, stat: Chapter,

Functional ability correlates with cognitive impairment in Parkinson's disease and Alzheimer's disease
Sabbagh, M. N; Lahti, T; Connor, D. J; Caviness, J. N; Shill, H; Vedders, L; Mahant, P; Samanta, J; Burns, R. S; Evidente, V. G. H; Driver-Dunckley, E; Reisberg, B; Bircea, S; Adler, C. H
2007 ;24(5):327-334, Dementia geriatric & cognitive disorders
Background/Aims: Previously we have shown that functional declines in Parkinson's disease (PD) and Alzheimer's disease (AD) correlate to global measures of cognitive decline. We now determine if the correlation between cognitive impairment and functional ability in PD is similar to that in AD using individual cognitive measures. Methods: 93 PD subjects and 124 AD/MCI subjects underwent the Functional Assessment Staging (FAST), the Global Deterioration Scale (GDS), and a neuropsychological battery. Results: In PD subjects, the FAST and GDS correlated significantly with Rey Auditory Verbal Learning Test (AVLT), Controlled Oral Word Association (COWA), Animal Fluency, and Stroop but not with Clock Draw or Judgment Line Orientation (JLO). In AD/MCI subjects, FAST and GDS correlated with all neuropsychological components except Stroop. In the AD/MCI group, the UPDRS significantly correlated with the FAST, GDS, MMSE, and all neuropsychological parameters except the Stroop. In the PD group, the motor UPDRS significantly correlated significantly with FAST, GDS, MMSE and all neuropsychological parameters except Digit Span, Stroop, Clock Draw and JLO. Conclusions: Similar to AD, functional decline in PD correlates with multiple measures of cognitive impairment. Some differences between PD and AD may be explained by the influence of motor disability and declines in visuospatial function in PD. (journal abstract)
— id: 76125, year: 2007, vol: 24, page: 327, stat: Journal Article,

Intraneuronal Abeta immunoreactivity is not a predictor of brain amyloidosis-beta or neurofibrillary degeneration
Wegiel, Jerzy; Kuchna, Izabela; Nowicki, Krzysztof; Frackowiak, Janusz; Mazur-Kolecka, Bozena; Imaki, Humi; Wegiel, Jarek; Mehta, Pankaj D; Silverman, Wayne P; Reisberg, Barry; Deleon, Mony; Wisniewski, Thomas; Pirttilla, Tuula; Frey, Harry; Lehtimaki, Terho; Kivimaki, Tarmo; Visser, Frank E; Kamphorst, Wouter; Potempska, Anna; Bolton, David; Currie, Julia R; Miller, David L
2007 Apr;113(4):389-402, Acta neuropathologica
Amyloid beta (Abeta) immunoreactivity in neurons was examined in brains of 32 control subjects, 31 people with Down syndrome, and 36 patients with sporadic Alzheimer's disease to determine if intraneuronal Abeta immunoreactivity is an early manifestation of Alzheimer-type pathology leading to fibrillar plaque formation and/or neurofibrillary degeneration. The appearance of Abeta immunoreactivity in neurons in infants and stable neuron-type specific Abeta immunoreactivity in a majority of brain structures during late childhood, adulthood, and normal aging does not support this hypothesis. The absence or detection of only traces of reaction with antibodies against 4-13 aa and 8-17 aa of Abeta in neurons indicated that intraneuronal Abeta was mainly a product of alpha- and gamma-secretases (Abeta(17-40/42)). The presence of N-terminally truncated Abeta(17-40) and Abeta(17-42) in the control brains was confirmed by Western blotting and the identity of Abeta(17-40) was confirmed by mass spectrometry. The prevalence of products of alpha- and gamma -secretases in neurons and beta- and gamma-secretases in plaques argues against major contribution of Abeta-immunopositive material detected in neuronal soma to amyloid deposit in plaques. The strongest intraneuronal Abeta(17-42) immunoreactivity was observed in structures with low susceptibility to fibrillar Abeta deposition, neurofibrillary degeneration, and neuronal loss compared to areas more vulnerable to Alzheimer-type pathology. These observations indicate that the intraneuronal Abeta immunoreactivity detected in this study is not a predictor of brain amyloidosis or neurofibrillary degeneration. The constant level of Abeta immunoreactivity in structures free from neuronal pathology during essentially the entire life span suggests that intraneuronal amino-terminally truncated Abeta represents a product of normal neuronal metabolism
— id: 71032, year: 2007, vol: 113, page: 389, stat: Journal Article,

Behavioral pathology in Alzheimer's disease rating scale (BEHAVE-AD): Spanish validation
Boada, M; Tarraga, L; Modinos, G; Diego, S; Reisberg, B
2006 JAN-FEB ;21(1):19-25, Neurologia (Barcelona, Spain)
Introduction. The Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) is a screening instrument for the evaluation of behavioral disturbances in Alzheimer's patients. Our aim was to validate the BEHAVE-AD test in Spanish, intended for use in routine clinical practice. Method. We assessed the validity of the BEHAVE-AD in 79 nursing-home patients with diagnosis criteria of dementia, scoring 4 or higher on the Global Deterioration Scale (GDS) scale, by developing a crossed validated form between the Neuropsychiatric Inventory-Questionnaire (NPI-Q) and BEHAVE-AD tests. Both instruments were rated by an expert clinician. In order to study the concurrent validity of some of the BEHAVE-AD subscales, we compared the Cohen-Mansfield Agitation Inventory (CMAI) and the Hamilton Depression Rating Scale (HDRS) tests. Results. The Pearson correlation index between the BEHAVE-AD test and the NPI-Q, was significant but moderate (r=0.694). Pearson's correlation between BEHAVE-AD's symptoms scale and NPI-Q's severity scale was r=0.698. When comparing BEHAVE-AD's global evaluation scale (caregiver's disturbance) and NPI-Q's distress scale, the correlation index was 0.535. Conclusions. The BEHAVE-AD Spanish version offers the possibility to use a screening tool for the detection of neuropsychiatric symptoms in dementia patients, also applicable to nursing home residents, administered by an expert clinician
— id: 98080, year: 2006, vol: 21, page: 19, stat: Journal Article,

Longitudinal CSF and MRI biomarkers improve the diagnosis of mild cognitive impairment
de Leon, M J; DeSanti, S; Zinkowski, R; Mehta, P D; Pratico, D; Segal, S; Rusinek, H; Li, J; Tsui, W; Saint Louis, L A; Clark, C M; Tarshish, C; Li, Y; Lair, L; Javier, E; Rich, K; Lesbre, P; Mosconi, L; Reisberg, B; Sadowski, M; DeBernadis, J F; Kerkman, D J; Hampel, H; Wahlund, L-O; Davies, P
2006 Mar;27(3):394-401, Neurobiology of aging
The diagnosis of Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI) is limited because it is based on non-specific behavioral and neuroimaging findings. The lesions of Alzheimer's disease: amyloid beta (Abeta) deposits, tau pathology and cellular oxidative damage, affect the hippocampus in the earlier stages causing memory impairment. In a 2-year longitudinal study of MCI patients and normal controls, we examined the hypothesis that cerebrospinal fluid (CSF) markers for these pathological features improve the diagnostic accuracy over memory and magnetic resonance imaging (MRI)-hippocampal volume evaluations. Relative to control, MCI patients showed decreased memory and hippocampal volumes and elevated CSF levels of hyperphosphorylated tau and isoprostane. These two CSF measures consistently improved the diagnostic accuracy over the memory measures and the isoprostane measure incremented the accuracy of the hippocampal volume achieving overall diagnostic accuracies of about 90%. Among MCI patients, over 2 years, longitudinal hippocampal volume losses were closely associated with increasing hyperphosphorylated tau and decreasing amyloid beta-42 levels. These results demonstrate that CSF biomarkers for AD contribute to the characterization of MCI
— id: 62680, year: 2006, vol: 27, page: 394, stat: Journal Article,

Mild cognitive impairment
Gauthier, Serge; Reisberg, Barry; Zaudig, Michael; Petersen, Ronald C; Ritchie, Karen; Broich, Karl; Belleville, Sylvie; Brodaty, Henry; Bennett, David; Chertkow, Howard; Cummings, Jeffrey L; de Leon, Mony; Feldman, Howard; Ganguli, Mary; Hampel, Harald; Scheltens, Philip; Tierney, Mary C; Whitehouse, Peter; Winblad, Bengt
2006 Apr 15;367(9518):1262-1270, Lancet
Mild cognitive impairment is a syndrome defined as cognitive decline greater than expected for an individual's age and education level but that does not interfere notably with activities of daily life. Prevalence in population-based epidemiological studies ranges from 3% to 19% in adults older than 65 years. Some people with mild cognitive impairment seem to remain stable or return to normal over time, but more than half progress to dementia within 5 years. Mild cognitive impairment can thus be regarded as a risk state for dementia, and its identification could lead to secondary prevention by controlling risk factors such as systolic hypertension. The amnestic subtype of mild cognitive impairment has a high risk of progression to Alzheimer's disease, and it could constitute a prodromal stage of this disorder. Other definitions and subtypes of mild cognitive impairment need to be studied as potential prodromes of Alzheimer's disease and other types of dementia
— id: 71967, year: 2006, vol: 367, page: 1262, stat: Journal Article,

Prediction of longitudinal cognitive decline in normal elderly with subjective complaints using electrophysiological imaging
Prichep, L S; John, E R; Ferris, S H; Rausch, L; Fang, Z; Cancro, R; Torossian, C; Reisberg, B
2006 Mar;27(3):471-481, Neurobiology of aging
An extensive literature reports changes in quantitative electroencephalogram (QEEG) with aging and a relationship between magnitude of changes and degree of clinical deterioration in progressive dementia. Longitudinal studies have demonstrated QEEG differences between mild cognitively impaired (MCI) elderly who go on to decline and those who do not. This study focuses on normal elderly with subjective cognitive complaints to assess the utility of QEEG in predicting future decline within 7 years. Forty-four normal elderly received extensive clinical, neurocognitive and QEEG examinations at baseline. All study subjects (N = 44) had only subjective complaints but no objective evidence of cognitive deficit (evaluated using the Global Deterioration Scale [GDS] score, GDS stage = 2) at baseline and were re-evaluated during 7-9 year follow-up. Baseline QEEGs of Decliners differed significantly (p < 0.0001, by MANOVA) from Non-Decliners, characterized by increases in theta power, slowing of mean frequency, and changes in covariance among regions, especially on the right hemisphere. Using logistic regression, an R2 of 0.93 (p < 0.001) was obtained between baseline QEEG features and probability of future decline, with an overall predictive accuracy of 90%. These data indicate high sensitivity and specificity for baseline QEEG as a differential predictor of future cognitive state in normal, subjectively impaired elderly
— id: 63733, year: 2006, vol: 27, page: 471, stat: Journal Article,

Open-label extension studies and misinformation - In reply
Reisberg, B; Doody, R; Schmitt, F; Ferris, S
2006 JUL ;63(7):1036-1037, Archives of neurology
— id: 66455, year: 2006, vol: 63, page: 1036, stat: Journal Article,

Diagnostic criteria in dementia: a comparison of current criteria, research challenges, and implications for DSM-V
Reisberg, Barry
2006 Sep;19(3):137-146, Journal of geriatric psychiatry & neurology
Planning is being initiated for the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders 5th ed. (DSM-V). Therefore, the dementia diagnosis criteria in the American Psychiatric Association's DSM-IV-TR (4th ed, text revision, 2000) have been compared with the World Health Organization's International Classification of Diseases (10th revision, 1992). Critiques are based primarily on (a) internal consistency and validity of the classification, (b) historical development of the field, (c) conclusions of consensus conferences, and (d) current knowledge and practice. It is suggested that (1) the entire category be labeled 'cognitive disorders,' to better characterize this group of disorders, (2) there is no longer any scientific basis for the presenile versus senile dementia dichotomy at age 65, (3) Alzheimer's disease no longer should have unique status as a 'diagnosis of exclusion,' (4) future manuals should incorporate knowledge regarding the clinical manifestation and course of Alzheimer's disease and other dementias, and (5) the classification 'Pick's disease' should be broadened to 'frontotemporal dementias.' DSM-V should incorporate continuing advances in the neuroscience knowledge base and understanding of these disorders
— id: 94419, year: 2006, vol: 19, page: 137, stat: Journal Article,

A 24-week open-label extension study of memantine in moderate to severe Alzheimer disease
Reisberg, Barry; Doody, Rachelle; Stoffler, Albrecht; Schmitt, Frederick; Ferris, Steven; Mobius, Hans Jorg
2006 Jan;63(1):49-54, Archives of neurology
BACKGROUND: This study is an extension of a 28-week, randomized, double-blind, placebo-controlled study of memantine in 252 patients with moderate to severe Alzheimer disease. OBJECTIVE: To evaluate long-term memantine treatment in moderate to severe Alzheimer disease. DESIGN, SETTING, AND PATIENTS: Open-label, 24-week extension trial. Raters remained blind to the patients' initial study treatment. Patients (n = 175) were enrolled from the previous double-blind study in an outpatient setting. INTERVENTION: Twenty mg of memantine was given daily. MAIN OUTCOME MEASURES: Efficacy assessments from the double-blind study were continued and safety parameters were monitored. RESULTS: Patients who switched to memantine treatment from their previous placebo therapy experienced a significant benefit in all main efficacy assessments (functional, global, and cognitive) relative to their mean rate of decline with placebo treatment during the double-blind period (P<.05). The completion rate for the extension phase of the study was high (78%) and the favorable adverse event profile for memantine therapy was similar to that seen in the double-blind study. CONCLUSION: These results extend previous findings that demonstrated the efficacy and safety of memantine in the treatment of patients with moderate to severe Alzheimer disease
— id: 62642, year: 2006, vol: 63, page: 49, stat: Journal Article,

Clinical Features of Severe Dementia: Staging
Reisberg, Barry; Wegiel, Jerzy; Franssen, Emile; Kadiyala, Sridhar; Auer, Stefanie; Souren, Liduin; Sabbagh, Marwan; Golomb, James
Severe dementia New York, NY, US: John Wiley & Sons Ltd, 2006,
(from the chapter) From a clinical perspective the phase of Severe Dementia can be defined as, 'the portion of the dementia disease process in which cognitive deficits are of sufficient magnitude as to compromise an otherwise healthy person's capacities to independently perform basic activities of daily life, such as dressing, bathing, and toileting'. From this clinical perspective, the phase of Severe Dementia is enormously important since this is clearly the portion of the disease in which both caregivers, individually, and society, more generally, are most burdened. Equally importantly, the Severe Dementia phase is the portion of dementia in which patients may suffer to the greatest extent. It is also a portion of dementia in which interventions can be most meaningful in alleviating distress and suffering for patients. For the most part, such interventions require an understanding of the clinical process of the Severe Dementia phase. In the context of Alzheimer's disease (AD), Global Deterioration Scale (GDS) (Reisberg el al., 1982) stage 5 has been termed Moderate AD, GDS stage 6 has been termed Moderately Severe AD, and GDS stage 7 has been termed Severe AD (e.g. see Reisberg and Saeed, 2004). The Severe Dementia phase includes GDS stage 6 and GDS stage 7, Moderately Severe and Severe AD. The definition of the Severe Dementia phase provided above is consistent with the GDS stage definitions for the AD stages. It is also consistent with the definitions used for currently approved treatments for AD. At the upper end of the severity spectrum, the cholinesterase inhibitors have been approved for the treatment of mild to moderate AD in the United States and elsewhere, using definitions which are consistent with the definition of the Severe Dementia phase proposed in this chapter (i.e. Moderate AD is less severe than the Severe Dementia phase range provided herein). However, the terminology which has been employed in the Clinical Dementia Rating (CDR) (Hughes et al., 1982; Berg, 1988; Morris, 1993), is not consistent with the definitions proposed in this chapter. Specifically, the CDR 2 stage, termed 'Moderate Dementia', in the CDR scale publications, is a stage in which patients require assistance in dressing, hygiene, keeping of personal effects. Clearly, the CDR 2 stage, as well as the subsequent CDR 3 stage, fits the definition of Severe Dementia proposed herein. Therefore, these CDR 2 and CDR 3 stages will be discussed in the context of severe dementia in this chapter.
— id: 4126, year: 2006, vol: , page: 83, stat: Chapter,

ADCS Prevention Instrument Project: ADCS-clinicians' global impression of change scales (ADCS-CGIC), self-rated and study partner-rated versions
Schneider, Lon S; Clark, Christopher M; Doody, Rachelle; Ferris, Steven H; Morris, John C; Raman, Rema; Reisberg, Barry; Schmitt, Frederick A
2006 Oct-Dec;20(4 Suppl 3):S124-S138, Alzheimer disease & associated disorders
BACKGROUND: Because primary prevention trials will require large samples and modest treatment effects are expected, the use of standard clinician-administered, clinic-based measures are unlikely to be feasible. There is a need for proxy-administered outcome measures. The goal of the Alzheimer's Disease Cooperative Study (ADCS) Prevention Instrument Project was to conduct a simulated Alzheimer disease prevention trial in 650 nondemented elderly (Ferris et al, 2006). This involved comparison of data acquisition from both home and clinic and the use of both informant-ratings and self-ratings. Important outcomes included clinical global impressions of change (CGIC) as indicators of clinically meaningful change. Such ratings provide verification that the effects of a medication as measured on rating scales are readily observable and clinically meaningful. One objective was to develop self-rated and study partner-rated CGICs optimized for nondemented elderly or people with very early Alzheimer disease. An important consideration was whether global assessments are specific and sensitive measures of change during a prevention trial. METHODS: A self-administered CGIC and a study partner-rated CGIC were developed to be used either in the clinic or at home. Using 3-month follow-up data, we determined its reliability and validity with 317 subject-partner pairs. We compared subject-ratings with partner-ratings, clinic-based with home-based ratings, and ratings based on severity as determined by the Clinical Dementia Rating scale. RESULTS: There were no differences between clinic and home ratings. Overall, 24% of subjects rated themselves, and 10% of study partners rated the subjects, as minimally to markedly improved. Subjects and partners agreed to within 1 point of their ratings 83% of the time on the 7-point scale. There were weak correlations, generally <0.20, with change scores of selected clinical rating scales. DISCUSSION: The CGICs behaved as expected, showing no overall change over 3 months, no difference between administrations at home compared with clinics, and concurrent validity. Some subjects tended to rate themselves better than their partners rated them. These analyses show the potential for using home-based CGICs which can be completed with minimal supervision and allow assessments of potential preventative interventions
— id: 94418, year: 2006, vol: 20, page: S124, stat: Journal Article,

Alzheimer's disease and medical disease conditions: a prospective cohort study
Boksay, Istvan; Boksay, Ezster; Reisberg, Barry; Torossian, Carol; Krishnamurthy, Mahesh
2005 Dec;53(12):2235-2236, Journal of the American Geriatrics Society
— id: 83585, year: 2005, vol: 53, page: 2235, stat: Journal Article,

Diffusion tensor imaging of frontal white matter microstructure in early Alzheimer's disease: a preliminary study
Choi, Steven J; Lim, Kelvin O; Monteiro, Isabel; Reisberg, Barry
2005 Mar;18(1):12-19, Journal of geriatric psychiatry & neurology
Several investigators have suggested that the pathological progression of Alzheimer's disease appears to recapitulate the developmental maturation pattern, a process termed retrogenesis. Diffusion tensor imaging was used to test the hypothesis that the microstructural integrity of superior frontal and temporal white matter, one of the last regions to mature, would be reduced in vivo in early Alzheimer's disease. Five consecutive slices, from the orbitofrontal to periventricular frontal regions, as well as temporal and corpus callosal white matter regions, were sampled. Fractional anisotropy, mean diffusivity, axial diffusion, and radial diffusion of 10 patients with early Alzheimer's disease and 10 age-similar healthy control subjects were compared. Patients with Alzheimer's disease were found to have significantly reduced fractional anisotropy, increased mean diffusivity, and increased radial diffusion in superior frontal white matter. These data suggest that the integrity of periventricular frontal white matter rather than orbitofrontal white matter appears to be altered in early Alzheimer's disease and that the white matter abnormalities involve compromised myelin, consistent with the retrogenesis theory
— id: 94421, year: 2005, vol: 18, page: 12, stat: Journal Article,

CSF biomarkers add to delayed recall and hippocampal volume in diagnosing MCI
De Leon, MJ; DeSanti, S; Zinkowski, R; Mehta, PD; Pratico, D; Rusinek, H; Li, J; Tsui, W; Reisberg, B; Zhan, J; Rich, K; Davies, P
2005 DEC ;30(53):S17-S17, Neuropsychopharmacology
— id: 59555, year: 2005, vol: 30, page: S17, stat: Journal Article,

New treatments and new knowledge of AD: an integrated view from biomolecular and clinical perspectives
Reisberg, B
2005 JAN 1 ;17(1):33-34, International psychogeriatrics
— id: 62385, year: 2005, vol: 17, page: 33, stat: Journal Article,

Commentary on "Diagnosis of Alzheimer's disease: Two decades of progress." Symptomatology and biomolecular basis of Alzheimer's: A synthesis
Reisberg, Barry
2005 Oct;1(2):102-106, Alzheimer's & Dementia
— id: 100673, year: 2005, vol: 1, page: 102, stat: Journal Article,

Alzheimer's Disease
Reisberg, Barry; Javed, Ali; Kenowsky, Sunnie; Auer, Stefanie R
Medical aspects of disability : a handbook for the rehabilitation professional New York, NY, US: Springer Publishing Co, 2005,
This chapter provides an outline of global cognitive, functional, and behavioral changes in normal aging and progressive Alzheimer's Disease (AD). Treatment implications are also provided.
— id: 4103, year: 2005, vol: , page: 79, stat: Chapter,

Is the functional decline of Parkinson's disease similar to the functional decline of Alzheimer's disease?
Sabbagh, M. N; Silverberg, N; Bircea, S; Majeed, B; Samant, S; Caviness, J. N; Reisberg, B; Adler, C. H
2005 ;11(5):311-315 Aug, Parkinsonism & related disorders
Since many Parkinson's disease (PD) subjects develop dementia, we determined whether the correlation between functional and cognitive decline seen in Alzheimer's disease (AD) is seen in PD. Seventy-five PD subjects with and without dementia and 103 AD/MCI subjects underwent the Functional Assessment Staging (FAST), the Global Deterioration Scale (GDS), the UPDRS motor portion, and the MMSE. In AD/MCI subjects, changes in FAST and GDS scores correlated with MMSE (rho=-0.814, P<0.001; rho=-0.840, P<0.001, respectively). In PD subjects, the FAST and GDS also correlated with MMSE (rho=-0.675, P<0.001; rho=-0.647, P<0.001, respectively). The UPDRS correlated with the GDS and FAST more closely in PD than in AD. Similar to AD, functional declines in PD correlates with cognitive decline and may be influenced by motor disability in PD. (journal abstract)
— id: 59259, year: 2005, vol: 11, page: 311, stat: Journal Article,

Vascular burden of the brain
O'Brien, John; Reisberg, Barry; Erkinjuntti, Timo
2003 ;15 Suppl 1:7-10, International psychogeriatrics
— id: 94420, year: 2003, vol: 15 Suppl 1, page: 7, stat: Journal Article,

Memantine in moderate-to-severe Alzheimer's disease
Reisberg, Barry; Doody, Rachelle; Stoffler, Albrecht; Schmitt, Frederick; Ferris, Steven; Mobius, Hans Jorg
2003 Apr 3;348(14):1333-1341, New England journal of medicine
BACKGROUND: Overstimulation of the N-methyl-D-aspartate (NMDA) receptor by glutamate is implicated in neurodegenerative disorders. Accordingly, we investigated memantine, an NMDA antagonist, for the treatment of Alzheimer's disease. METHODS: Patients with moderate-to-severe Alzheimer's disease were randomly assigned to receive placebo or 20 mg of memantine daily for 28 weeks. The primary efficacy variables were the Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus) and the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory modified for severe dementia (ADCS-ADLsev). The secondary efficacy end points included the Severe Impairment Battery and other measures of cognition, function, and behavior. Treatment differences between base line and the end point were assessed. Missing observations were imputed by using the most recent previous observation (the last observation carried forward). The results were also analyzed with only the observed values included, without replacing the missing values (observed-cases analysis). RESULTS: Two hundred fifty-two patients (67 percent women; mean age, 76 years) from 32 U.S. centers were enrolled. Of these, 181 (72 percent) completed the study and were evaluated at week 28. Seventy-one patients discontinued treatment prematurely (42 taking placebo and 29 taking memantine). Patients receiving memantine had a better outcome than those receiving placebo, according to the results of the CIBIC-Plus (P=0.06 with the last observation carried forward, P=0.03 for observed cases), the ADCS-ADLsev (P=0.02 with the last observation carried forward, P=0.003 for observed cases), and the Severe Impairment Battery (P<0.001 with the last observation carried forward, P=0.002 for observed cases). Memantine was not associated with a significant frequency of adverse events. CONCLUSIONS: Antiglutamatergic treatment reduced clinical deterioration in moderate-to-severe Alzheimer's disease, a phase associated with distress for patients and burden on caregivers, for which other treatments are not available
— id: 34295, year: 2003, vol: 348, page: 1333, stat: Journal Article,

Staging: relevance for trial design in vascular burden of the brain
Reisberg, Barry; Ferris, Steven H; Oo, Thet; Franssen, Emile
2003 ;15 Suppl 1:231-239, International psychogeriatrics
Cerebrovascular small vessel disease is now believed to be the major source of vascular burden of the brain. Cerebrovascular small vessel disease and Alzheimer's disease appear to represent pathophysiologic and clinical continua, rather than dichotomous entities. It appears that common etiopathologic mechanisms underlie the clinical presentation of both of these conditions. Therefore, the staging procedures that have been developed for the clinical continuum of age-associated memory impairment, mild cognitive impairment, and the progressive dementia of Alzheimer's disease appear to be applicable for the same continua in cerebrovascular small vessel disease. Although temporal and prognostic aspects have been studied for the Alzheimer's-related portions of this clinical staging continuum, they remain to be elucidated for cerebrovascular small vessel disease
— id: 58979, year: 2003, vol: 15 Suppl 1, page: 231, stat: Journal Article,

The neuropathology of Alzheimer dementia
Weigel J; Wisniewski T; Reisberg B; Silverman W
Dementia : presentations, differential diagnosis, and nosology Baltimore MD : Johns Hopkins Press, 2003,
— id: 4978, year: 2003, vol: , page: 89, stat: Chapter,

Slower rates of Alzheimer's disease-related neuronal loss in the entorhinal cortex in Down's syndrome compared to sporadic Alzheimer's disease
Kuchna, I; Wegiel, J; Silverman, W; Pirttila, T; Visser, F; Wisniewski, T; Reisberg, B
2002 Jul-Aug;23(1):1763-, Neurobiology of aging
— id: 32436, year: 2002, vol: 23, page: 1763, stat: Journal Article,

Activities of daily living (ADL) in MCl and early dementia: The ADL international scale (ADL-IS)
Reisberg, B; Faiz, S; Finkel, S; Overall, J; Erzigkeit, H
2002 Jul-Aug;23(1):107-, Neurobiology of aging
— id: 32408, year: 2002, vol: 23, page: 107, stat: Journal Article,

Long-term treatment with the NMDA antagonist memantine: Results of a 24-week, open-label extension study in moderately severe- to-severe Alzheimer's disease
Reisberg, B; Ferris, S; Mobius, HJ; Schmitt, F; Doody, R
2002 Jul-Aug;23(1):2039-, Neurobiology of aging
— id: 32439, year: 2002, vol: 23, page: 2039, stat: Journal Article,

Retrogenesis in
Reisberg, B; Franssen, E
2002 Jul-Aug;23(1):1938-, Neurobiology of aging
— id: 32438, year: 2002, vol: 23, page: 1938, stat: Journal Article,

Retrogenesis: Pathophysiology and treatment relevance
Reisberg, B; Franssen, EH; Brula, AQ; Oo, T
2002 NOV ;63(11):1078-1078, Journal of clinical psychiatry
— id: 33281, year: 2002, vol: 63, page: 1078, stat: Journal Article,

Evidence and mechanisms of retrogenesis in Alzheimer's and other dementias: management and treatment import
Reisberg, Barry; Franssen, Emile H; Souren, Liduin E M; Auer, Stefanie R; Akram, Imran; Kenowsky, Sunnie
2002 Jul-Aug;17(4):202-212, American journal of Alzheimer's disease & other dementias
Retrogenesis is the process by which degenerative mechanisms reverse the order of acquisition in normal development. Alzheimer's disease (AD) and related conditions in the senium have long been noted to resemble 'a return to childhood' Previously, we noted that the functional stages of AD precisely and remarkably recapitulated the acquisition of the same functional landmarks in normal human development. Subsequent work indicated that this developmental recapitulation also applied to the cognitive and related symptoms in AD. Remarkably, further investigations revealed that the same neurologic 'infantile' reflexes, which mark the emergence from infancy in normal development, are equally robust indicators of corresponding stages in AD. Neuropathologic and biomolecular mechanisms for these retrogenic processes are now evident. For example, the pattern of myelin loss in AD appears to mirror the pattern of myelin acquisition in normal development. Also, recent findings indicate that mitogenic factors become reactivated in AD, and, consequently, the most actively 'growing' brain regions are the most vulnerable. Because of this robust retrogenic process, the stages of AD can be translated into corresponding developmental ages (DAs). These DAs can account for the overall management and care needs of AD patients. A science of AD management can be formulated on the basis of the DA of the Alzheimer's patient, taking into consideration differences of AD from normal development as well as homologies
— id: 34292, year: 2002, vol: 17, page: 202, stat: Journal Article,

Measuring cognition in advanced Alzheimer's disease for clinical trials
Schmitt, F A; Cragar, D; Ashford, J W; Reisberg, B; Ferris, S; Mobius, H J; Stoffler, A
2002 ;348(62):135-148, Journal of neural transmission. Supplementum
Measurement of cognitive dysfunction and treatment response in the early stages of Alzheimer's disease (AD) has used such scales as the Mini-Mental State Examination (MMSE) and the AD Assessment Scale (ADAS). With the exception of clinical rating scales, however, there are only a few objective measures of cognition for tracking progression in advanced AD. Given renewed interest in potential therapies for advanced AD, objective measures of cognition are important for the adequate evaluation of change due to AD progression or therapy. Several cognitive measures for advanced AD are reviewed. One measure, the Severe Impairment Battery (SIB) is reviewed in detail. Preliminary analyses from a trial of memantine show significant change on the SIB in memory (p < 0.001) and visuospatial functions (p < 0.02) over six-months with a trend for language and praxis. Data from a donepezil trial also highlight the importance of accurate assessment in advanced AD
— id: 34296, year: 2002, vol: 348, page: 135, stat: Journal Article,

Intraneuronal accumulation of N-terminally truncated amyloid beta
Wegiel, J; Kuchna, I; Miller, D; Mehta, P; Wegiel, J; Wisniewski, T; Reisberg, B; Silverman, W
2002 May;61(5):164-, Journal of neuropathology & experimental neurology
— id: 28188, year: 2002, vol: 61, page: 164, stat: Journal Article,

Vascular fibrosis and calcification in the hippocampus in aging, Alzheimer disease, and Down syndrome
Wegiel, J; Kuchna, I; Wisniewski, T; de Leon, M J; Reisberg, B; Pirttila, T; Kivimaki, T; Lehtimaki, T
2002 Apr;103(4):333-343, Acta neuropathologica
Study of the hippocampal formation of 82 subjects, including 25 control subjects from 33 to 83 years of age, 34 subjects with Alzheimer disease (AD) from 65 to 89 years of age, and 23 subjects with Down syndrome (DS) from 33 to 72 years of age, revealed hippocampal vasculopathy with fibrosis and calcification (VFC) in 40% of control, 59% of AD, and 4% of DS subjects. VFC starts in the precapillaries/capillaries in the molecular layer of the dentate gyrus (DG) and expands to the granule cell and polymorphic cell layer of the DG, and to the stratum lacunosum/molecular in the CA1 sector. Vasculopathy spreads from the tail to the body and, in a few cases, to the head of the hippocampal formation. Light and electron microscopy reveal thickening of the vascular wall with fibrosis, calcification, and enforcement of the astrocyte interface with vessels with anchorage densities associated with hemidesmosome-like structures. In moderately and severely affected cases, fragmentation and removal of calcified and occluded vessels result in local reduction of vascular network. In two AD subjects, severe vascular calcification extending from the tail to the head of the hippocampal formation was associated with loss of almost all neurons in the CA1 sector and in the subiculum proper, corresponding to hippocampal sclerosis. The topography of affected vessels and the patterns of neuronal loss reflect the middle hippocampal artery distribution with its precapillary/capillary network. The similar prevalence of vasculopathy in the AD group and in the age-matched control group, and the presence of hippocampal VFC in only one subject in the DS cohort, 96% of which is affected by Alzheimer-type pathology, oppose the link between AD and this form of vasculopathy. However, severe VFC affects the pattern of AD pathology locally by deletion of neurofibrillary degeneration and beta-amyloidosis in the CA1 sector, subiculum proper, and the molecular layer of the dentate gyrus. Hippocampal VFC appears to be a form of vascular pathology with a unique predilection for the middle hippocampal artery and corresponding capillary network, which results in patchy neuronal loss in moderately affected subjects and in almost total neuronal loss in the area of impaired blood supply in severely affected subjects. These observations suggest an etiologic link between hippocampal VFC and hippocampal sclerosis
— id: 34298, year: 2002, vol: 103, page: 333, stat: Journal Article,

Prediction of cognitive decline in normal elderly subjects with 2-[(18)F]fluoro-2-deoxy-D-glucose/poitron-emission tomography (FDG/PET)
de Leon MJ; Convit A; Wolf OT; Tarshish CY; DeSanti S; Rusinek H; Tsui W; Kandil E; Scherer AJ; Roche A; Imossi A; Thorn E; Bobinski M; Caraos C; Lesbre P; Schlyer D; Poirier J; Reisberg B; Fowler J
2001 Sep 11;98(19):10966-10971, Proceedings of the National Academy of Sciences of the United States of America
Neuropathology studies show that patients with mild cognitive impairment (MCI) and Alzheimer's disease typically have lesions of the entorhinal cortex (EC), hippocampus (Hip), and temporal neocortex. Related observations with in vivo imaging have enabled the prediction of dementia from MCI. Although individuals with normal cognition may have focal EC lesions, this anatomy has not been studied as a predictor of cognitive decline and brain change. The objective of this MRI-guided 2-[(18)F]fluoro-2-deoxy-d-glucose/positron-emission tomography (FDG/PET) study was to examine the hypothesis that among normal elderly subjects, EC METglu reductions predict decline and the involvement of the Hip and neocortex. In a 3-year longitudinal study of 48 healthy normal elderly, 12 individuals (mean age 72) demonstrated cognitive decline (11 to MCI and 1 to Alzheimer's disease). Nondeclining controls were matched on apolipoprotein E genotype, age, education, and gender. At baseline, metabolic reductions in the EC accurately predicted the conversion from normal to MCI. Among those who declined, the baseline EC predicted longitudinal memory and temporal neocortex metabolic reductions. At follow-up, those who declined showed memory impairment and hypometabolism in temporal lobe neocortex and Hip. Among those subjects who declined, apolipoprotein E E4 carriers showed marked longitudinal temporal neocortex reductions. In summary, these data suggest that an EC stage of brain involvement can be detected in normal elderly that predicts future cognitive and brain metabolism reductions. Progressive E4-related hypometabolism may underlie the known increased susceptibility for dementia. Further study is required to estimate individual risks and to determine the physiologic basis for METglu changes detected while cognition is normal
— id: 26662, year: 2001, vol: 98, page: 10966, stat: Journal Article,

Addition of a frequency-weighted score to the Behavioral Pathology in Alzheimer's Disease Rating Scale: the BEHAVE-AD-FW: methodology and reliability
Monteiro IM; Boksay I; Auer SR; Torossian C; Ferris SH; Reisberg B
2001 Jan;16 Suppl 1(1):5s-24s, European psychiatry
The Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) is a well-established instrument, designed to assess potentially remediable behavioral symptoms in Alzheimer's disease (AD) patients as well as to evaluate treatment outcome. It consists of 25 symptoms grouped into seven categories. Each symptom is scored on the basis of severity on a four-point scale. A knowledgeable caregiver is queried and items are scored on the basis of symptoms noted in the preceding two weeks. Reliability, construct validity and criterion validity data for the BEHAVE-AD have previously been published. Because of the significance of psychopathology in dementia, it is necessary to optimally describe and define the nature, magnitude and prevalence of behavioral symptomatology. Accordingly, a frequency component was added to each of the 25 items of the BEHAVE-AD scale. The objective of the present report is to describe this new Behavioral Pathology in Alzheimer's Disease Frequency-Weighted Severity Scale (BEHAVE-AD-FW) and to establish its inter-rater reliability. In this investigation the BEHAVE-AD-FW scale was administered to caregivers of 28 patients with either mildly impaired cognitive function or a dementia diagnosis. Two clinicians separately and independently rated the responses. Analyses determined that the intraclass correlation coefficients (ICCs) for the frequency component varied between 0.86 and 0.97 for each of the seven BEHAVE-AD categories (p(s) < 0.001). ICCs for the frequency-weighted scores (item severity score x item frequency score) ranged from 0.69 to 0.98 for the seven symptom categories (p(s) < 0.001). For the BEHAVE-AD-FW total scores, the ICC was 0.91 (P < 0.001). These results indicate that the frequency-weighted component is a reliable addition to the BEHAVE-AD scale
— id: 26696, year: 2001, vol: 16 Suppl 1, page: 5s, stat: Journal Article,

The Alzheimer's disease activities of daily living international scale (ADL-IS)
Reisberg B; Finkel S; Overall J; Schmidt-Gollas N; Kanowski S; Lehfeld H; Hulla F; Sclan SG; Wilms HU; Heininger K; Hindmarch I; Stemmler M; Poon L; Kluger A; Cooler C; Bergener M; Hugonot-Diener L; Robert PH; Antipolis S; Erzigkeit H
2001 Jun;13(2):163-181, International psychogeriatrics
BACKGROUND: Activities of daily living (ADL) deficits are integral components of dementia disorders, and ADL measures are among the most robust markers of the course of Alzheimer's disease (AD). Despite this acknowledged importance, no clearly useful ADL instrument for cross-cultural application in pharmacologic trials in the early stages of AD had been available. METHOD: An international effort was launched to develop an ADL scale for pharmacologic trials in early AD. Steps taken from 1990 to the present included: (1) international scientific working group meetings and reviews, (2) reviews of existing measures, (3) collating of existent, nonredundant items, (4) querying experts for new items, (5) interviews with informants and subjects in the USA, France, and Germany, toward the identification of potential new items, (6) identification of an item pool based upon these procedures, (7) creation of a trial instrument, (8) piloting of this instrument, and (9) refinement of the scale based upon statistical analysis of the pilot data. Final item selection was based upon: (1) relevance for > or = 80% of subjects in severity-stratified USA and German samples; (2) absence of gender and national biases; (3) significant (p <.05) discrimination between (a) normal versus mildly impaired and (b) mildly impaired versus moderately to moderately severely impaired subjects; and (4) Global Deterioration Scale (GDS) scores accounting for > or = 12% of variance in the item after controlling for age and gender. RESULTS: An ADL scale consisting of 40 items that correlate with the global and cognitive progress of AD is developed for international usage in pharmacologic trials in incipient, mild, moderate, and moderately severe AD. The scale contains 40 items falling within 13 ADL categories. The 40-item scale is shown to have .81 correlation with GDS staging, .81 with mental status assessment (Mini-Mental State Examination), and .81 with a psychometric test (the SKT) (p values < .001). CONCLUSION: This scale can be used to measure therapeutic response in AD
— id: 26631, year: 2001, vol: 13, page: 163, stat: Journal Article,

Shift from fibrillar to nonfibrillar Abeta deposits in the neocortex of subjects with Alzheimer disease
Wegiel J; Bobinski M; Tarnawski M; Dziewiatkowski J; Popovitch E; Bobinski M; Lach B; Reisberg B; Miller DC; De Santi S; De Leon MJ
2001 Feb;3(1):49-57, Journal of Alzheimer's Disease
A morphometric study of amyloid-beta-positive plaques in the neocortex of eight non-demented people from 68 to 82 years of age and 17 subjects with late-stage Alzheimer disease (GDS stage 7/FAST stages 7a-f) from 73 to 93 years of age shows a shift from prevalence of fibrillar plaques to prevalence of nonfibrillar plaques. In the aged, non-demented subjects, about 4/mm^2 plaques are detectable in the neocortex, and the majority are fibrillar plaques. Specifically, 64% found to be classical fibrillar and Thioflavin-S-positive bright primitive plaques. A lower percentage of pale primitive plaques (35%) relatively small proportion of plaques that are poor in thioflavin S-positive fibrils. The numerical density of plaques in the severe stage of AD increases to about 41/mm^2. Severely demented subjects appear to maintain an active process of fibrillar plaque formation. This is reflected in the presence of 3% bright primitive plaques. Severely demented subjects also manifest plaque degradation, reflected in the presence of 22% and 48% percentages of classical fibrillar plaques in non-demented subjects and in the end stage of disease suggest that once activated, the process of fibrillar plaque formation persists at a somewhat stable rate during the whole course of brain amyloidosis
— id: 34297, year: 2001, vol: 3, page: 49, stat: Journal Article,

Fibrillar amyloid-beta affects neurofibrillary changes but only in neurons already involved in neurofibrillary degeneration
Wegiel J; Bobinski M; Tarnawski M; Dziewiatkowski J; Popovitch E; Miller DC; Wisniewski T; Golomb J; de Leon MJ; Reisberg B
2001 Jun;101(6):585-590, Acta neuropathologica
The aim of this study of the cerebral cortex of 8 non-demented elderly subjects and of 17 subjects in the severe stage of Alzheimer's disease (AD) (Global Deterioration Scale stage 7/Functional Assessment Staging procedure stage 7a-f) was to examine the relationships between amyloid-beta (Abeta) deposits and neurofibrillary degeneration. The study shows that neuronal processes with neurofibrillary changes are detectable in only a minority of fibrillar plaques: from 31% to 49% of fibrillar plaques within frontal, temporal, parietal, limbic, occipital, and insular cortices. The correlations observed between the numerical densities of neurons with neurofibrillary tangles (NFTs) and the densities of Thioflavin-S-positive fibrillar plaques with neurofibrillary changes (r=0.61; P<0.01) indicate that neurofibrillary pathology in neocortical plaques reflects the topography and rate of neurofibrillary changes in neocortical neurons. The accumulation of abnormally phosphorylated tau in only some plaques indicates that fibrillar Abeta enhances paired helical filament accumulation locally only in dystrophic neurites already involved in neurofibrillary degeneration. The lack of correlation between the number of neurons with neurofibrillary changes and the number of all Thioflavin-S-positive fibrillar plaques (with and without neurofibrillary changes) suggests that beta-amyloidosis does not contribute to initiation of neurofibrillary degeneration in neurons
— id: 34299, year: 2001, vol: 101, page: 585, stat: Journal Article,

The 1999 IPA/Bayer Research Awards
Reisberg B
2000 Mar;12(1):9-14, International psychogeriatrics
— id: 11718, year: 2000, vol: 12, page: 9, stat: Journal Article,

Results of a placebo-controlled 6-month trial with memantine in moderate to severe Alzheimer's disease (AD)
Reisberg, B; Ferris, S; Sahin, K; Windscheif, U; Mobius, H J
2000 Sept 09-13;10(Supplement 3):S363-S364, European neuropsychopharmacology
— id: 15779, year: 2000, vol: 10, page: S363, stat: Journal Article,

Postmortem findings in patients with Alzheimer's disease
Wu, H; Miller, D C; Reisberg, B; Waisman, J
2000 ;80(Suppl 1):7A-7A, Laboratory investigation
— id: 15796, year: 2000, vol: 80, page: 7A, stat: Journal Article,

Equilibrium and limb coordination in mild cognitive impairment and mild Alzheimer's disease
Franssen EH; Souren LE; Torossian CL; Reisberg B
1999 Apr;47(4):463-469, Journal of the American Geriatrics Society
OBJECTIVE: To examine changes in equilibrium and limb coordination in normal aging, mild cognitive impairment, and moderate cognitive impairment associated with early probable Alzheimer's disease (AD), by means of parametric clinical measures. DESIGN: Case series SETTING: Out-patient clinic. PARTICIPANTS: A consecutive sample of 365 community-residing ambulatory volunteers (137 men, 228 women; mean age 70.4 +/- 9.4 years; mean educational attainment 14.6 +/- 3.1 years), who were followed in an ongoing longitudinal study of aging and AD, comprising cognitively intact individuals, persons with mild cognitive impairment, and patients with mild AD. MEASUREMENTS: For general magnitude of cognitive function, the Global Deterioration Scale (GDS). For cognition, the Mini-Mental State Examination (MMSE). Equilibrium was assessed with parametric measurements of single leg stance (SLS) and tandem walking (TW). Limb coordination was assessed with parametric measurements of foot tapping (FT), alternating pronation and supination (PS), and sequential finger to thumb tapping (FTH). MAIN RESULTS: After adjustment for age, persons with mild cognitive impairment or mild AD had significantly poorer performance on parametric clinical tests of equilibrium and limb coordination compared with cognitively intact individuals (P < .05). CONCLUSIONS: Changes in equilibrium and limb coordination are clinically demonstrable in persons with mild cognitive impairment and mild AD using simple parametric tests. Such tests could potentially identify individuals with increased risk of falling. Early diagnosis and treatment of conditions that can jeopardize equilibrium and limb coordination, as well as balance and coordination training, might help cognitively impaired older people to maintain optimal function and may decrease the risk of falls and injuries
— id: 6082, year: 1999, vol: 47, page: 463, stat: Journal Article,

Neuropsychological prediction of decline to dementia in nondemented elderly
Kluger A; Ferris SH; Golomb J; Mittelman MS; Reisberg B
1999 Winter;12(4):168-179, Journal of geriatric psychiatry & neurology
This study examined whether baseline neuropsychological performance in elderly assessed at a research clinic could accurately predict subsequent decline to dementia. Logistic regression analyses were applied to (1) 213 nondemented elderly with a Global Deterioration Scale (GDS) score of 1, 2, or 3, of whom 74 (35%) subsequently declined to any diagnosis of dementia, and (2) a diagnostically more restricted subset of this sample (N = 179), of whom 56 (31%) declined to a diagnosis of probable Alzheimer's disease (AD). The mean follow-up intervals were 3.8 and 3.7 years, respectively. A small set of baseline neuropsychological measures (especially a Paragraph Delayed Recall Test) significantly differentiated decliners from nondecliners to dementia or AD, after accounting for the contribution of age, sex, education, follow-up interval, and the rating of global clinical status. When examined in combination with the other factors or alone, the cognitive tests produced reasonably high specificities (91%-97%) and sensitivities (73%-89%). Using the obtained regression model, a similar level of classification accuracy was replicated on an independent sample of 119 nondemented elderly. A subanalysis of the high-risk GDS 3 subgroup indicated that cut scores from the paragraph test distinguished nondecliners from decliners (overall accuracies 87%-91%), implying that this assessment may accurately predict future cognitive status in elderly with mild cognitive impairment
— id: 8598, year: 1999, vol: 12, page: 168, stat: Journal Article,

Retrogenesis: clinical, physiologic, and pathologic mechanisms in brain aging, Alzheimer's and other dementing processes
Reisberg B; Franssen EH; Hasan SM; Monteiro I; Boksay I; Souren LE; Kenowsky S; Auer SR; Elahi S; Kluger A
1999 ;249 Suppl 3:28-36, European archives of psychiatry & clinical neuroscience
Data from clinical, electrophysiologic, neurophysiologic, neuroimaging and neuropathologic sources indicates that the progression of brain aging and Alzheimer's disease (AD) deterioration proceeds inversely to human ontogenic acquisition patterns. A word for this process of degenerative developmental recapitulation, 'retrogenesis', has been proposed. These retrogenic processes provide new insights into the pathologic mechanism of AD deterioration. An understanding of retrogenic phenonmena can also result in insights into the applicability of retrogenic pathologic mechanisms for non-AD dementing disorders. Management strategies based upon retrogenesis have recently been proposed. Retrogenic pathophysiology also points to previously unexplored pharmacologic approaches to dementia prevention and treatment
— id: 8580, year: 1999, vol: 249 Suppl 3, page: 28, stat: Journal Article,

Towards a science of Alzheimer's disease management: a model based upon current knowledge of retrogenesis
Reisberg B; Kenowsky S; Franssen EH; Auer SR; Souren LE
1999 Mar;11(1):7-23, International psychogeriatrics
BACKGROUND: General relationships between dotage and infancy and childhood have been acknowledged for more than two millennia. Recent findings indicate precise relationships between functional, praxic, and feeding changes in the course of the degenerative dementia of Alzheimer's disease (AD) and inverse corresponding developmental sequences. Similar inverse relationships between AD and human development can be described for cognition and language skills; for physiologic measures of electroencephalographic activity, brain glucose metabolism, and developmental neurologic reflex changes; and for the neuropathologic and neuroanatomic progression of these processes. In AD, these processes may be termed 'retrogenesis.' The relevance of the retrogenesis model for AD management is explored. METHOD: The functional stages of AD can be translated into developmental age equivalents that can be utilized to explicate observed changes in the disease. RESULTS: The retrogenesis-based developmental age model can usefully inform an understanding of the general care needs, emotional and behavioral changes, and activity needs of the AD patient. This model must be amended by necessary caveats regarding physical differences, variations in age-associated pathology, differences in social and societal reactions, and differences in background between AD patients and their developmental age 'peers.' CONCLUSIONS: Knowledge of retrogenesis and the developmental age of the AD patient can form a nidus for the development of a nascent science of disease management. Such a science must ultimately incorporate not only appropriate caveats but also relevant universal human needs, such as those for dignity, love, and movement
— id: 6077, year: 1999, vol: 11, page: 7, stat: Journal Article,

Cerebellar atrophy in Alzheimer's disease-clinicopathological correlations
Wegiel J; Wisniewski HM; Dziewiatkowski J; Badmajew E; Tarnawski M; Reisberg B; Mlodzik B; De Leon MJ; Miller DC
1999 Feb 6;818(1):41-50, Brain research
Morphometry of the cerebellum of 11 subjects who died in the severe, final stage of Alzheimer's disease (AD) and of five age-matched subjects without dementia revealed significant atrophy in the AD group, with a decrease in the volume of the molecular layer by 24% and of the granular layer by 22% in comparison with controls. The 32% decrease in the total number of Purkinje cells that was observed correlates with the atrophy of the molecular layer, whereas the 30% reduction in the total number of granule cells correlates with the atrophy of the molecular and granular layers. A unique pattern of Alzheimer-type pathology was observed in the cerebellum: (1) there were no neurofibrillary changes in the cerebellum of either the control or the AD subjects, (2) there was almost the same extent of leptomeningeal and cortical amyloid angiopathy in the normal aged subjects and in the AD patients, and (3) the presence of plaques was noted in the AD group, but not in the control group. This pattern of pathology suggests that two factors might be considered in the etiopathogenesis of cerebellar atrophy: (1) transneuronal degeneration and neuronal loss resulting from primary pathologic changes in cerebral structures and (2) parenchymal cerebellar ss-amyloidosis. The correlation between the temporal duration of AD and both the decrease of the total number of granule cells (r=0.86, p<0.01) and the volumetric loss of the molecular (r=0.73, p<0.05) and granular (r=0.93, p<0.001) layers of the cerebellar cortex indicates that these cerebellar atrophic changes are likely to be related to the basic pathologic process of AD. Similarly, the correlation between the most complex parameter the atrophy of the cerebellar cortex and the Functional Assessment Staging (FAST) measure of the clinical severity of AD at the time of demise (r=0.63, p<0.05) as well as with the duration of AD (r=0.78, p<0.01) indicates that cerebellar pathology, when viewed holistically, evolves continuously in association with clinical changes throughout the clinically manifest course of AD.
— id: 7465, year: 1999, vol: 818, page: 41, stat: Journal Article,

Neuronal and volume loss in CA1 of the hippocampal formation uniquely predicts duration and severity of Alzheimer disease
Bobinski M; de Leon MJ; Tarnawski M; Wegiel J; Reisberg B; Miller DC; Wisniewski HM
1998 Sep 14;805(1-2):267-269, Brain research
In a series of multiple regression models predicting either duration or severity of Alzheimer disease (AD) patients, significant linear correlations were found consistently for the volume of CA1, the subiculum, and the entorhinal cortex. Similarly, the total number of neurons in CA1, CA4, and the subiculum was correlated significantly with both the duration and the severity of AD. A hierarchical multiple regression model was used to examine whether any of these intercorrelated measures had any unique relationship to disease duration or severity. The results showed that only CA1 demonstrated a unique contribution to the explained variance in predicting duration or severity of AD for volume and for neuronal numbers. These results indicate that in the hippocampal formation, volume and neuronal numbers of CA1 appear to show a unique relationship with clinical measures of AD.
— id: 7509, year: 1998, vol: 805, page: 267, stat: Journal Article,

Duration of neurofibrillary changes in the hippocampal pyramidal neurons
Bobinski M; Wegiel J; Tarnawski M; de Leon MJ; Reisberg B; Miller DC; Wisniewski HM
1998 Jul 13;799(1):156-158, Brain research
The total number of neurons with and without neurofibrillary changes in sectors CA1 to CA4, subiculum, and dentate gyrus of 16 subjects with Alzheimer disease (AD) was estimated. The duration of neurofibrillary changes was calculated on the basis of regressions between the duration of AD and neuronal numbers. In the CA1 and subiculum, it takes 3.4 and 5.4 years, respectively, for an intact neuron affected by neurofibrillary pathology to become a ghost tangle.
— id: 7508, year: 1998, vol: 799, page: 156, stat: Journal Article,

Reliability of routine clinical instruments for the assessment of Alzheimer's disease administered by telephone
Monteiro IM; Boksay I; Auer SR; Torossian C; Sinaiko E; Reisberg B
1998 Spring;11(1):18-24, Journal of geriatric psychiatry & neurology
We investigated the reliability, using a telephone interview procedure, of cognitive, functional, and behavioral scales in an elderly population with normal aging and dementia. Two clinicians performed the assessments: one performed the assessments in a telephone interview format and the other conducted the assessments at the clinic. The telephone interview always preceded the clinic evaluation (2-30 days apart), and both clinicians were blind to any previous evaluations of the patient. The intraclass correlation coefficients between the telephone interview and the ratings obtained by a different clinician on the clinic evaluation varied between 0.92 and 0.98 (P's < or = .001) for comprehensive test scores. These results indicate that a telephone interview format, although not a substitute for a face-to-face diagnostic evaluation, is a reliable procedure for obtaining the assessment modalities studied. These findings are particularly important in aged and dementia research populations where personal contact may not always be feasible
— id: 7694, year: 1998, vol: 11, page: 18, stat: Journal Article,

Management of fluoroquinolone resistance in Pseudomonas aeruginosa--outcome of monitored use in a referral hospital
Peterson LR; Postelnick M; Pozdol TL; Reisberg B; Noskin GA
1998 Aug;10(3):207-214, International journal of antimicrobial agents
We evaluated a strategy designed to improve useful activity of ciprofloxacin against Pseudomonas aeruginosa. Following changes in antimicrobial agent use made by the institutional Pharmacy and Therapeutic Drug Committee, monthly drug usage and microbial susceptibility records from June 1992 through October 1995 were reviewed. From July 1992 through October 1992 (Period 1), ciprofloxacin and ofloxacin usage represented 95 and 5% of total quinolone doses; from December 1992 to March 1993 (Period 2), ciprofloxacin represented 19%; from July 1993 to October 1993 (Period 3), ciprofloxacin usage represented 85%; from July 1994 to October 1994 (Period 4), ciprofloxacin represented 95%; and from July 1995 to October 1995 (Period 5), ciprofloxacin and ofloxacin respectively represented 98 and 2% of total quinolone doses. Comparison of the anti-pseudomonal activity of the two fluoroquinolones to ofloxacin use, ciprofloxacin use and total quinolone use during the entire observational period showed the highest (negative) correlation with ofloxacin use versus ofloxacin activity (y = -15.04x + 1367.99, r2 = 0.06, w = 0.126). Increased use of quinolones plus a change to primarily ofloxacin usage appeared to adversely affect the activity of both ofloxacin and ciprofloxacin against P. aeruginosa
— id: 34300, year: 1998, vol: 10, page: 207, stat: Journal Article,

Progression of Alzheimer's disease: variability and consistency: ontogenic models, their applicability and relevance
Reisberg B; Franssen EH; Souren LE; Auer S; Kenowsky S
1998 ;54:9-20, Journal of neural transmission. Supplementum
Much has been learned about the clinical symptomatology of Alzheimer's disease (AD) and ontogenic reciprocal relationships in the past few decades. It is now possible to describe and verify inexorable symptomatic sequences and corresponding temporal relationships. It is also possible to identify more variable symptoms in AD. Ontogenic models can be useful in providing a clearer understanding of the nature of AD symptomatology in terms of both consistency and variability. These models can also be informative in explicating the management needs of AD patients and the treatment possibilities of AD symptoms as well as the etiology of variability in AD symptoms
— id: 7753, year: 1998, vol: 54, page: 9, stat: Journal Article,

The GDS/FAST staging system
Auer S; Reisberg B
1997 ;9 Suppl 1:167-171, International psychogeriatrics
Staging methodologies are an essential tool in the assessment of disease severity in progressive dementing illness. Several different instruments have been developed for this purpose. One of the most widely used methodologies is the Global Deterioration Scale/Functional Assessment Staging (GDS/FAST) system. This system has been studied extensively and proven to be reliable and valid for staging dementia in Alzheimer's disease (AD) in diverse settings. One of the major advantages of this system is that it spans, demarcates, and describes the entire course of normal aging and progressive AD until the final substages of the disease process. Other advantages include: (a) greatly enhanced ability to track the longitudinal course of AD, (b) improved clinicopathologic observations of AD interrelationships, and (c) enhanced diagnostic, differential diagnostic, and prognostic information. This article presents a brief overview of the GDS/FAST staging system
— id: 12174, year: 1997, vol: 9 Suppl 1, page: 167, stat: Journal Article,

Relationships between regional neuronal loss and neurofibrillary changes in the hippocampal formation and duration and severity of Alzheimer disease
Bobinski M; Wegiel J; Tarnawski M; Bobinski M; Reisberg B; de Leon MJ; Miller DC; Wisniewski HM
1997 Apr;56(4):414-420, Journal of neuropathology & experimental neurology
The total numbers of neurons with and without neurofibrillary changes in the hippocampal subdivisions were estimated in 16 subjects with Alzheimer disease (AD) and in 5 normal elderly controls. On the basis of clinical symptoms, AD patients were subdivided into relatively less (AD-1. Functional Assessment Staging [FAST] stages 7a to 7c) and more severely affected (AD-2, FAST stages 7e to 7f) patient groups. In the AD-1 group relative to controls, the total number of neurons was reduced only in CA1 and in the subiculum. In the AD-2 group, neuronal losses were found in all sectors of the cornu Ammonis and in the subiculum and ranged from 53% in CA3 to 86% in CA1. The dentate gyrus was the only hippocampal subdivision without significant neuronal loss. Within the combined AD patient groups, significant correlations were noted between both clinical stage and duration of AD and both the total number of neurons and the percentage of neurons with neurofibrillary changes in CA1, CA4, and the subiculum. Regression analyses predicted neuronal losses over the maximal observed duration of 22 years of 87% in CA1, 63% in CA4, and 77% in the subiculum. Our data suggest that over the course of AD, continuous neurofibrillary tangle formation and continuous neuronal loss occur in the hippocampal subdivisions. The rate of neuronal loss appears to be similar for CA1, CA4, and the subiculum
— id: 9448, year: 1997, vol: 56, page: 414, stat: Journal Article,

Frequency of hippocampal formation atrophy in normal aging and Alzheimer's disease
De Leon MJ; George AE; Golomb J; Tarshish C; Convit A; Kluger A; De Santi S; McRae T; Ferris SH; Reisberg B; Ince C; Rusinek H; Bobinski M; Quinn B; Miller DC; Wisniewski HM
1997 Jan-Feb;18(1):1-11, Neurobiology of aging
We used CT and MR to examine the frequency of occurrence of hippocampal formation atrophy (HA) in a research clinic population of 130 normal elderly, 72 nondemented patients with very mild memory and cognitive impairments (MCI), 73 mild Alzheimer's disease (AD) patients, and 130 patients with moderate to severe AD. HA was found in 29% of the normal elderly group and its frequency of occurrence was strongly related to increasing age. For normal elderly 60-75 years of age, 15% had HA: the proportion rose to 48% in subjects 76-90 years of age. Among the three groups of impaired patients, the frequencies of HA ranged from 78% in the MCI patients to 96% in the advanced AD group. Unlike the normal elderly group, the percentages were not related to age. In both the normal elderly group and MCI group disproportionately more males than females had HA. After controlling for learning and the effects of generalized brain changes as reflected in ventricular size, only in the normal group was HA associated with reduced delayed verbal recall performance. Follow-up examinations for 15 individuals with baseline HA. 4 who at entry were MCI and 11 probable AD, yielded clinical and neuropathologic diagnoses of AD in all cases. The results of the present study indicate that hippocampal formation atrophy is associated with memory and cognitive impairments. Further longitudinal and neuropathologic work is required to validate the relationship between hippocampal formation atrophy and AD
— id: 9449, year: 1997, vol: 18, page: 1, stat: Journal Article,

Neurologic markers of the progression of Alzheimer's disease
Franssen EH; Reisberg B
1997 ;9 Suppl 1:297-306, International psychogeriatrics
This article describes the results of studies conducted to determine the usefulness of reflex changes as markers of disease severity in Alzheimer's disease (AD). Standardized and quantified muscle stretch reflexes, cutaneous reflexes, and developmental (primitive) reflexes were studied in normal older adults, in individuals with mild memory impairment, and in patients with AD, in all clinical severity stages as assessed with the Global Deterioration Scale (GDS), the Mini-Mental State Examination (MMSE), and the Functional Assessment Staging (FAST) procedure. Changes in frequency and intensity of these individual reflex variables, as well as of variables consisting of combinations of these individual reflexes, appeared to be sensitive indicators of the progression of AD. These neurological reflex variables showed high Pearson correlations with the GDS (.72), the MMSE (.74), and the FAST (.80). Standardized quantified neurological reflex measures are useful as noncognitive, education-independent, and culture-independent markers of the course of AD
— id: 12173, year: 1997, vol: 9 Suppl 1, page: 297, stat: Journal Article,

Utility of developmental reflexes in the differential diagnosis and prognosis of incontinence in Alzheimer's disease
Franssen EH; Souren LE; Torossian CL; Reisberg B
1997 Jan;10(1):22-28, Journal of geriatric psychiatry & neurology
Four developmental reflexes, the tactile suck reflex, the palmar and plantar grasp reflexes, and the plantar extensor reflex, were examined in 784 individuals, including healthy elderly, cognitively and functionally mildly impaired individuals, and patients with Alzheimer's disease (AD) in all stages of clinical severity. The study population was classified into six categories of increasingly impaired functional performance, and prevalence of the four individual reflexes and of a summary reflex measure, consisting of a combination of these four reflexes, was determined for each category. Prevalence of all five reflex measures was more than six times higher for those categories that comprised only permanently doubly incontinent patients as compared to those categories that comprised only continent individuals (P < .001). Frequency of developmental reflexes rose sharply with the onset of progressive incontinence. Since the return of these reflexes in AD is associated with severe cortical dysfunction, it is concluded that these developmental reflexes are useful in differentiating incontinence of cortical origin from incontinence resulting from potentially reversible causes
— id: 7148, year: 1997, vol: 10, page: 22, stat: Journal Article,

Patterns of motor impairement in normal aging, mild cognitive decline, and early Alzheimer's disease
Kluger A; Gianutsos JG; Golomb J; Ferris SH; George AE; Franssen E; Reisberg B
1997 Jan;52(1):P28-P39, Journals of gerontology. Series B. Psychological sciences & social sciences
In order to determine the relationship between cognitive dysfunction and motor behavior in older adults, 41 cognitively normal elderly (NL), 25 cases exhibiting mild cognitive impairment (MI), and 25 patients with mild Alzheimer's disease (AD) were examined using a broad array to motor/psychomotor and cognitive tests. Relative to the NL group, MI individuals (at risk for future decline to AD) performed worse on tasks involving fine and complex motor function (e.g., tracking and manual dexterity). AD patients also exhibited motor dysfunction on tasks assessing relatively more rudimentary motor control. Motor tasks were able to distinguish NL vs MI and NL vs mild AD individuals as effectively as cognitive tests of memory and language. These results indicate that motor impairment is an important aspect of cognitive decline in older adults. Motor/psychomotor assessments may be comparably sensitive to traditional tests of cognitive function in identifying persons affected by the earliest stages of AD pathology
— id: 12424, year: 1997, vol: 52, page: P28, stat: Journal Article,

Motor/psychomotor dysfunction in normal aging, mild cognitive decline, and early Alzheimer's disease: diagnostic and differential diagnostic features
Kluger A; Gianutsos JG; Golomb J; Ferris SH; Reisberg B
1997 ;9 Suppl 1:307-316, International psychogeriatrics
To determine the association between cognitive dysfunction and motor behavior in older adults, 41 cognitively normal elderly (NL), 25 nondemented patients exhibiting mild cognitive impairment (MI) and at risk for future decline to dementia, and 25 patients with mild (early) Alzheimer's disease (AD) were examined using a wide array of motor/psychomotor and cognitive assessments. The three groups were recruited from an aging and dementia research center and were composed of well-characterized physically healthy volunteers, with similar ages and gender distributions. The outcome measures included 16 motor/psychomotor tests categorized a priori into gross, fine, and complex, as well as eight cognitive tests of memory and language. Relative to the NL group, MI individuals performed poorly on cognitive, fine, and complex motor measures but not on gross motor tests; AD patients performed worse on cognitive and all motor domains. Differences in complex motor function persisted after adjustment for performance on cognitive and on less complex motor tests. Classification analyses showed similar accuracies in discriminating NL from MI and NL from AD cases for both complex motor (79% and 92% accuracy, respectively) and cognitive tests (80% and 93% accuracy, respectively). Less complex motor tests produced poorer accuracies. Among nondemented subjects, education correlated with several cognitive scores but no motor scores. These results indicate that motor impairment is an important aspect of cognitive decline in older adults. Motor/psychomotor assessments were found to be comparably sensitive to traditional tests of cognitive function in identifying persons affected by the earliest stages of AD pathology and may improve identification of at-risk nondemented elderly, especially among diversely educated individuals
— id: 12172, year: 1997, vol: 9 Suppl 1, page: 307, stat: Journal Article,

Informant-rated activities-of-daily-living (ADL) assessments: results of a study of 141 items in the U.S.A., Germany, Russia, and Greece from the International ADL Scale Development Project
Lehfeld H; Reisberg B; Finkel S; Kanowski S; Wied V; Pittas J; Tsolaki M; Robert PH; Hulla F; Heininger K; Erzigkeit H
1997 ;11 Suppl 4(6):S39-S44, Alzheimer disease & associated disorders
The analyses of an international pilot study presented in this article focused on the development of a cross-nationally valid activities-of-daily-living (ADL) scale sensitive to therapeutic effects in patients with mild memory impairment and mild to moderately severe dementia. The present report, which is part of an ongoing international research project, describes field testing results for 141 informant-rated items. The comparability of samples investigated in research centers in the U.S.A., Germany, Russia, and Greece concerning cognitive decline was evaluated globally as well as psychometrically using the Global Deterioration Scale, the Short Cognitive Performance Test, and the Mini-Mental State Examination. In the participating countries, a composite ADL score discriminated well between different stages of cognitive impairment because of dementia. However, international differences between the applied measures were observed. A practical ADL scale showing therapeutic sensitivity and international utility, will be constructed from the 141 informant-rated items under investigation in this pilot work
— id: 34301, year: 1997, vol: 11 Suppl 4, page: S39, stat: Journal Article,

Diagnosis of Alzheimer's disease. Report of an International Psychogeriatric Association Special Meeting Work Group under the cosponsorship of Alzheimer's Disease International, the European Federation of Neurological Societies, the World Health Organization, and the World Psychiatric Association
Reisberg B; Burns A; Brodaty H; Eastwood R; Rossor M; Sartorius N; Winblad B
1997 ;9 Suppl 1:11-38, International psychogeriatrics
Current knowledge with respect to the diagnosis of Alzheimer's disease (AD) is reviewed. There is agreement that AD is a characteristic clinicopathologic entity that is amenable to diagnosis. The diagnosis of AD should no longer be considered one of exclusion. Rather, the diagnostic process is one of recognition of the characteristic features of AD and of conditions that can have an impact on presentation or mimic aspects of the clinicopathologic picture. The present availability of improved prognosis, management, and treatment strategies makes the proper, and state-of-the-art, diagnosis of AD a clinical imperative in all medical settings. Concurrently, information regarding the relevance and applicability of current diagnostic procedures in diverse cultural settings must continue to accrue
— id: 12175, year: 1997, vol: 9 Suppl 1, page: 11, stat: Journal Article,

Clinical global measures of dementia. Position paper from the International Working Group on Harmonization of Dementia Drug Guidelines
Reisberg B; Schneider L; Doody R; Anand R; Feldman H; Haraguchi H; Kumar R; Lucca U; Mangone CA; Mohr E; Morris JC; Rogers S; Sawada T
1997 ;11 Suppl 3:8-18, Alzheimer disease & associated disorders
Following is the report of the committee working on clinical global measures for antidementia drug guidelines. The concepts involved in global scales, the distinctions between change and severity scales, advantages and disadvantages of structured interviews, and anchoring of change scores are discussed, and selected existing clinical global scales are described. In addition, the committee assessed the utility of global scales in clinical trials for antidementia drugs. There was a consensus among the members of the working group on the following: (1) Clinical global scales are interview based; in most cases, they include information obtained from caregivers as well as directly from patients, but they can rely on information from the subject only. (2) Clinicians' global ratings are intended to assess clinically meaningful change based on multidimensional clinical assessment and take into account the clinical heterogeneity of dementia by assessing at least cognition, behavior, and functioning. (3) There are two distinct types of clinical global measures: (a) clinicians' interview-based global severity scales, which generally incorporate classification by stage or severity of illness and (b) clinicians' interview-based global change scales, which incorporate global assessment ratings of clinical change. The committee could not reach a consensus on whether global scales should be required in phase II and phase III clinical trials, or whether other specific assessments such as well-designed activities of daily living, cognition, and behavior measures could, when used in appropriate combinations, replace the global as assessments of clinical meaningfulness
— id: 7244, year: 1997, vol: 11 Suppl 3, page: 8, stat: Journal Article,

Validity and reliability of the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change. The Alzheimer's Disease Cooperative Study
Schneider LS; Olin JT; Doody RS; Clark CM; Morris JC; Reisberg B; Schmitt FA; Grundman M; Thomas RG; Ferris SH
1997 ;11 Suppl 2(4):S22-S32, Alzheimer disease & associated disorders
This article reports the development and psychometric properties of the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC). At present, a number of unvalidated CGIC scales are used in clinical trials, with various methods for making ratings. The ADCS-CGIC was designed on the basis of a survey of ADCS clinicians and by adapting existing instruments. It includes an organized but unstructured format, with which a clinician can address clinically relevant change. The instrument's reliability and validity were assessed in a prospective trial of Alzheimer's disease (AD) and healthy subjects over a 12-month period. It showed good short-term reliability at 1 and 2 months, with 90 and 94% of AD subjects, respectively, rated as having changed not at all or only minimally. The ADCS-CGIC's face validity was demonstrated by untreated. AD subjects rated as having worsened over time at both 6 months (56% rated as having worsened) and 12 months (81% rated as having worsened), whereas only 2% of control subjects showed minimal worsening. As a measure of predictive validity, ADCS-CGIC ratings at 12 months were significantly associated with change on four severity scales. As with other measures, change ratings were sensitive to dementia severity. Moderately impaired subjects showed greater worsening than other subjects. ADCS-CGIC ratings of greater worsening were made after the informant interview, regardless of whether informants or subjects were interviewed first. The ADCS-CGIC is a valid and reliable instrument for use in clinical trials
— id: 18807, year: 1997, vol: 11 Suppl 2, page: S22, stat: Journal Article,

Neuromotor changes in Alzheimer's disease: implications for patient care
Souren LE; Franssen EH; Reisberg B
1997 Jul;10(3):93-98, Journal of geriatric psychiatry & neurology
As a result of the neuropathologic process of Alzheimer's disease (AD), significant changes occur in neuromotor function (e.g., paratonia and compulsive grasping). These changes become manifest in the moderately severe stage of AD, when patients begin to require ongoing assistance with activities of daily life (ADL), and they are prominent in the severe stage of AD, when patients are continuously dependent on a caregiver. Patients in these stages often display behavioral disturbances during care activities. These disturbing behaviors result not only from cognitive impairment, but also from a patient's physical inability to cooperate with the caregiver. When care management strategies take into account the characteristic physical restrictions resulting from the neuromotor changes that accompany advanced AD, the caregiving process may be significantly facilitated
— id: 7920, year: 1997, vol: 10, page: 93, stat: Journal Article,

Behavioral symptoms in dementia: community-based research
Auer SR; Monteiro IM; Reisberg B
1996 ;8 Suppl 3:363-366, International psychogeriatrics
— id: 7105, year: 1996, vol: 8 Suppl 3, page: 363, stat: Journal Article,

The Empirical Behavioral Pathology in Alzheimer's Disease (E-BEHAVE-AD) Rating Scale
Auer SR; Monteiro IM; Reisberg B
1996 Summer;8(2):247-266, International psychogeriatrics
A clinician should not rely entirely upon a caregiver's report regarding behavioral pathology when planning a treatment strategy. Direct observational evaluation instruments as well as caregiver-based assessments are necessary. A new scale for the empirical (observational) evaluation of behavioral symptoms in Alzheimer's disease (AD) and related dementias, the Empirical Behavioral Pathology in Alzheimer's Disease Rating Scale (E-BEHAVE-AD) was developed. Interrater reliability of this new assessment instrument was examined. Additionally, the relationship between the observed occurrence of behavioral symptomatology on this new rating instrument was compared with the occurrence using a similarly designed, caregiver-based instrument. The interrater reliability study consisted of two raters who simultaneously evaluated 20 dementia patients. The comparative study employed a cross-sectional design (N = 49). Individuals were evaluated in an outpatient clinic setting. The study population consisted of cognitively normal individuals and dementia patients. Evaluations included the new, observationally based behavioral assessment (the E-BEHAVE-AD), a caregiver-based behavioral assessment (the Behavioral Pathology in Alzheimer's Disease Rating Scale; BEHAVE-AD), a clinical global measure (the Global Deterioration Scale), and a mental status assessment (the Mini-Mental State Examination). The interrater reliability study revealed an intraclass correlation coefficient of .97 (p < .01) for total scores on the new E-BEHAVE-AD rating scale. The correlation coefficient for the amount of agreement on the presence of symptoms in six symptomatic categories between caregiver-based information about the patient's behavioral pathology assessed on the BEHAVE-AD and the clinician's observations assessed with the new E-BEHAVE-AD rating instrument was .51 (p < .01). The new E-BEHAVE-AD rating instrument showed excellent interrater reliability. Furthermore, there was a statistically significant relationship between clinician observation of the occurrence of behavioral pathology assessed using the E-BEHAVE-AD and caregiver-reported pathology assessed with the BEHAVE-AD. However, the magnitude of the correlation between these measures indicated that the majority of variance was independent and nonoverlapping. Consequently, these data support theoretical models suggesting that the assessment of behavioral pathology in dementia might ideally encompass both direct observational and caregiver-report approaches, using measures such as the E-BEHAVE-AD as well as measures such as the BEHAVE-AD
— id: 12661, year: 1996, vol: 8, page: 247, stat: Journal Article,

Reliability of the Modified Ordinal Scales of Psychological Development: a cognitive assessment battery for severe dementia
Auer SR; Reisberg B
1996 Summer;8(2):225-231, International psychogeriatrics
Two reliability studies were performed on a recently developed cognitive assessment battery for severe dementia. The method, the Modified Ordinal Scales of Psychological Development (M-OSPD), is based on the Piagetian developmental model of sensorimotor functions. Procedures have been adapted from this test battery, which was originally applied to infants and small children, for the assessment of remaining cognitive capacity in severe dementia. Two independent interrater reliability studies were conducted. In these studies, two different raters simultaneously evaluated patients with severe dementia. One interrater reliability study was performed in a nursing home setting (Study 1), and the other reliability study consisted of a sample of community-residing patients (Study 2). The Global Deterioration Scale and the Mini-Mental State Examination were used to assess dementia severity. Study 1 (N = 22) resulted in an intraclass correlation coefficient (ICC) of .99 (p < .01) for the M-OSPD total score. Study 2 (N = 19) resulted in an ICC of .96 (p < .01) for the M-OSPD total score. The M-OSPD proved to be a reliable instrument in these studies. This cognitive assessment measure can provide meaningful information regarding the cognitive abilities of late-stage dementia patients. Until recently, these late-stage dementia patients had been considered untestable in studies that utilized conventional psychometric and mental status evaluation measures
— id: 12662, year: 1996, vol: 8, page: 225, stat: Journal Article,

Neurofibrillary pathology--correlation with hippocampal formation atrophy in Alzheimer disease
Bobinski M; Wegiel J; Wisniewski HM; Tarnawski M; Bobinski M; Reisberg B; De Leon MJ; Miller DC
1996 Nov-Dec;17(6):909-919, Neurobiology of aging
The three-dimensionally reconstructed hippocampal formations in three patients with very severe, immobile Alzheimer disease (AD) and three age-matched nondemented individuals were examined for a correlation between atrophy of hippocampal formation subdivisions and neurofibrillary changes, neuronal loss, and extent of amyloid deposition in plaques and vessels. In AD, a similar severe volume loss was observed in both cellular layers and layers composed of fibers. A strong correlation between the decrease in the volume of hippocampal formation subdivisions and the decrease in the total number of neurons suggests a causative role for neuronal loss in hippocampal formation volumetric loss. Strong regional correlations between the relative decreases in the total number of neurons and the relative increases in the total number of neurofibrillary tangles implicates neurofibrillary pathology as a possible etiologic proximate factor in neuronal and volumetric loss in the hippocampal formation of AD patients
— id: 9446, year: 1996, vol: 17, page: 909, stat: Journal Article,

Medical conditions in Alzheimer's disease patients with 4/4 isotype of apolipoprotein E
Boksay, I.; Tchernkov, K.; Myint, Z.; Reisberg, B.; Wisniewski, T.
1996 ;17(4 SUPPL.):S125-S126, Neurobiology of aging
— id: 97598, year: 1996, vol: 17, page: S125, stat: Journal Article,

Staging methods for the assessment of dementia: Perspectives
Cohen-Mansfield J; Reisberg B; Bonnema J; Berg L; Dastoor DP; Pfeffer RI; Cohen GD
1996 May;57(5):190-198, Journal of clinical psychiatry
Most dementias in old age are characterized by a progressive course with interindividual variability in pattern and rate of progression. Developing a system for staging such dementia poses a challenge in capturing this variability in a system that will afford comparisons among individuals and predictions of future change. Several core questions underlie the development of such systems: (1) Is there a definable order in which abilities are lost? (2) Which skills and functions should be considered essential for the staging of dementia and what is their relative weight? (3) Can the different skills be captured within one staging system? (4) How is the whole range of function captured, and are the differences between stages clearly defined? (5) Which populations can be rated with each staging system? The determination of this last question is based on understanding which other medical conditions may interfere with the course of dementia and how prior characteristics, such as education, affect ratings on specific scales for the staging of dementia. Several systems for staging dementia in older adults are described. These include the Clinical Dementia Rating, the Global Deterioration Scale/Brief Cognitive Rating Scale/Functional Assessment Staging System, the Six Clinical Phases of Cognitive Decline, the Hierarchic Dementia Scale, and the Functional Capacity Scale. Some aspects of the utility of these systems are reviewed, and the issues for further research are discussed
— id: 34302, year: 1996, vol: 57, page: 190, stat: Journal Article,

Clinical evaluation of global change in Alzheimer's disease: identifying consensus
Olin JT; Schneider LS; Doody RS; Clark CM; Ferris SH; Morris JC; Reisberg B; Schmitt FA
1996 Oct;9(4):176-180, Journal of geriatric psychiatry & neurology
It is important that clinicians who rate global change as part of Alzheimer's disease (AD) clinical drug trials agree on a relevant set of behaviors and information to be considered in formulating their rating. Yet, consensus among raters has been difficult to establish, and inter-rater reliability of clinical global impression of change (CGIC) ratings has been low. In preparation for the development of a new CGIC scale to be used in AD clinical trials, the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC), we surveyed clinicians at sites comprising the National Institute on Aging-sponsored ADCS participating centers to identify whether or not consensus regarding CGICs exists. Overall, respondents reported that a CGIC should include an assessment of the patient's function and mental status, a care giver interview, and a standardized set of questions, and it should take approximately 20 minutes per interview. Depending on a patient's level of impairment, raters consider different areas of behavior in formulating a CGIC rating. These findings demonstrate the considerable consensus regarding the CGIC rating process, and were integrated into the design of the ADCS-CGIC, currently in use
— id: 18808, year: 1996, vol: 9, page: 176, stat: Journal Article,

Behavioral intervention approaches to the treatment and management of Alzheimer's disease: a research agenda
Reisberg B
1996 ;8 Suppl 1:38-44, International psychogeriatrics
— id: 7241, year: 1996, vol: 8 Suppl 1, page: 38, stat: Journal Article,

Behavioral disturbances of dementia: an overview of phenomenology and methodologic concerns
Reisberg B; Auer SR; Monteiro I; Boksay I; Sclan SG
1996 ;8 Suppl 2:169-180, International psychogeriatrics
Behavioral disturbances in dementia are some of the most burden-some features with which the caregivers must cope. These symptoms are particularly important because they are likely to be responsive to both pharmacological and nonpharmacological intervention strategies. Before the 1980s, rating scales for patients suffering from dementia did not separate cognitive features from noncognitive behavioral symptoms. This was a major problem because the evolution and course of behavioral symptoms in dementias, such as Alzheimer's disease, is different from the evolution and course of cognitive and cognition-related symptomatology. Before appropriate rating scales could be developed for the assessment of behavioral disturbances in dementia, the specific nature of these disturbances had to be described in the medical literature. Publications in the late 1980s described the specific behavioral disturbances occurring in dementia patients in detail for the first time. The rating scales that have been developed from these studies are as reliable as cognitive assessment measures. Instruments are now available that are based on information provided by the caregiver or that are based on observation of the patient made by the clinician. Construct validity, reliability, and the differences in methodology of these scales are compared in this overview. Using these scales will enable clinicians to assess pharmacological and nonpharmacological intervention strategies for behavioral symptoms in dementia with enhanced sensitivity
— id: 7242, year: 1996, vol: 8 Suppl 2, page: 169, stat: Journal Article,

Behavioral pathology in Alzheimer's disease (BEHAVE-AD) rating scale
Reisberg B; Auer SR; Monteiro IM
1996 ;8 Suppl 3:301-308, International psychogeriatrics
— id: 7243, year: 1996, vol: 8 Suppl 3, page: 301, stat: Journal Article,

Mortality and temporal course of probable Alzheimer's disease: a 5-year prospective study
Reisberg B; Ferris SH; Franssen EH; Shulman E; Monteiro I; Sclan SG; Steinberg G; Kluger A; Torossian C; de Leon MJ; Laska E
1996 Summer;8(2):291-311, International psychogeriatrics
Alzheimer's disease (AD) is associated with an increased mortality in comparison with aged control populations. The relationship between the clinical and the temporal course of AD has not been well studied over significant intervals. Community-residing patients with probable AD (N = 103, 42 men, mean age = 70.2 +/- 8.0 years) were studied at baseline on demographic and clinical variables, including measures of global deterioration (Global Deterioration Scale; GDS), mental status and cognition (e.g., Mini-Mental State Examination; MMSE), and functional impairment (Functional Assessment Staging; FAST). Baseline characteristics included a GDS range of Stage 4, 5, or 6 (38.8%, 39.8%, and 21.4%, respectively) and a mean MMSE score of 15.4 +/- 5.6. The mean follow-up interval was 4.6 +/- 1.4 years. Follow-ups were done blind to baseline measures and when necessary were conducted in residential and nursing home settings. Of locatable subjects (n = 95, 92%), 30 (31.6%) were decreased. Survivors (n = 65) had a mean GDS stage of 6.2 +/- 0.9 and a mean MMSE score of 5.1 +/- 6.9; 51% had MMSE scores of 0. Increased age and male gender, but not baseline clinical dementia variables, increased the risk of death (ps < .01). Change in clinical variables correlated significantly with time elapsed (r = .32, p < .05, for MMSE change, to r = .48, p < .001, for GDS change). Significant variance in temporal change (i.e., time elapsed) was accounted for by change in two of the five clinical measures studied (i.e., GDS and FAST; multiple r = .53). The results support previous estimates of mean duration of the GDS and FAST stages. For subjects with probable AD followed over approximately 5 years, clinical variables changed significantly over time in survivors. However, the majority of temporal variance in the course of AD remains unexplained
— id: 9450, year: 1996, vol: 8, page: 291, stat: Journal Article,

Overview of methodologic issues for pharmacologic trials in mild, moderate, and severe Alzheimer's disease
Reisberg B; Franssen EH; Bobinski M; Auer S; Monteiro I; Boksay I; Wegiel J; Shulman E; Steinberg G; Souren LE; Kluger A; Torossian C; Sinaiko E; Wisniewski HM; Ferris SH
1996 Summer;8(2):159-193, International psychogeriatrics
To address the issue of mild, moderate, and severe Alzheimer's disease (AD), it is necessary to initially establish some agreement on terminology. In recent decades, these terms have frequently been defined using screening instrument scores with measures such as the Mini-Mental State Examination (MMSE). There are many problems with this approach, perhaps the most salient of which is that it has contributed to the total and tragic neglect of patients with severe AD. An alternative approach to the classification of AD severity is staging. This approach has advanced to the point where moderately severe and severe AD can be described in detail. Procedures for describing this previously neglected latter portion of AD have recently been extensively validated. Staging is also uniquely useful at the other end of the severity spectrum, in differentiating early aging brain/behavior changes, incipient AD, and mild AD. Temporally, with staging procedures, it is possible to track the course of AD approximately three times more accurately than with the MMSE. The net result of the advances in AD delineation is that issues such as prophylaxis, modification of course, treatment of behavioral disturbances, loss of ambulation, progressive rigidity, and the development of contractures in AD patients can now be addressed in a scientifically meaningful way that will hopefully bestow much benefit in AD patients and those who care for them
— id: 12663, year: 1996, vol: 8, page: 159, stat: Journal Article,

Atrophy of hippocampal formation subdivisions correlates with stage and duration of Alzheimer disease
Bobinski M; Wegiel J; Wisniewski HM; Tarnawski M; Reisberg B; Mlodzik B; de Leon MJ; Miller DC
1995 Jul-Aug;6(4):205-210, Dementia
The hippocampal formations of 13 subjects with severe Alzheimer disease [AD; Global Deterioration Scale (GDS) stage 7] and of 5 age-matched subjects without symptoms of dementia were reconstructed from serial sections. Functional assessment staging (FAST) was used at the time of demise to assess 9 patients at stages 7a-c (incipient averbal and nonambulatory) and 4 patients at stages 7e-f (immobile). The duration of the disease from FAST stage 5 until demise ranged from 2 to 8 years in the first of these subgroups, and from 10 to 13 years in the second. The volumes of the entire hippocampal formation and of the cornu ammonis, its sectors and layers, the dentate gyrus, the subicular complex, and the entorhinal cortex were calculated. Hippocampal formation volume decreased by 36% in the incipient averbal and nonambulatory patients and by 60% in the severely functionally impaired immobile patients, in comparison with controls. In the final substages of AD, immobile patients exhibited significant atrophy, in comparison with controls, in the cornu ammonis and all of its sectors and layers except CA4, the subicular complex and all of its parts, and the entorhinal cortex (p < 0.05). Within the AD patient group, significant correlations were noted between both the magnitude of functional severity and the duration of AD and the volumes of most hippocampal formation subdivisions studied. For the cornu ammonis, subicular complex, and entorhinal cortex, volumetric loss correlations with FAST stage 7 ordinally enumerated substages were r = -0.71, -0.79, and -0.62, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
— id: 9451, year: 1995, vol: 6, page: 205, stat: Journal Article,

NEURONAL LOSS IN HIPPOCAMPAL-FORMATION SUBDIVISIONS CORRELATES WITH DURATION AND STAGE OF ALZHEIMER-DISEASE
BOBINSKI, M; WEGIEL, J; WISNIEWSKI, HM; TAMAWSKI, M; BOBINSKA, M; REISBERG, B; MLODZIK, B; DELEON, M; MILLER, DC
1995 MAY ;54(3):428-428, Journal of neuropathology & experimental neurology
— id: 87306, year: 1995, vol: 54, page: 428, stat: Journal Article,

Temporal order of cognitive and functional loss in a nursing home population
Cohen-Mansfield J; Werner P; Reisberg B
1995 Sep;43(9):974-978, Journal of the American Geriatrics Society
OBJECTIVE: The order in which cognition and the ability to perform activities of daily living (ADLs) are lost in an institutionalized aged population was examined. Understanding the order of loss of function is important for preparing caregivers and planning of care. METHOD: The conditional probabilities of the inability to perform activity A when there exists the inability to perform activity B were explored in secondary analyses of cross-sectional data describing 408 nursing home residents. Residents' abilities to perform ADLs were rated by nursing staff using Linn and Linn's Rapid Disability Rating Scale (RDRS-2); cognitive functioning was rated by social workers and nursing staff using a modified version of Reisberg et al.'s Brief Cognitive Rating Scale (BCRS, with 4 axes: orientation, concentration, recent memory, and past memory). RESULTS: The results regarding ADLs confirm previous findings of a natural order of loss of ability (from the one lost first to last): bathing, dressing, grooming, toileting, walking, and eating. The examination of order in the loss of concentration, recent memory, past memory, and orientation revealed that these seem to be lost concurrently when the cutpoint was 3 (i.e., relatively normal functioning vs. moderate and severe dementia). When the cutpoint was 6 (i.e., severe dementia vs. higher levels of functioning), the order that emerged was: recent memory, past memory, concentration, and orientation. CONCLUSIONS: Although there is a significant relationship between loss of ability to perform ADLs and stage of cognitive impairment, the loss of any specific ADL is not uniquely related to any one stage of cognitive deterioration in this diverse population. This may be explained by the high prevalence of disease in this institutionalized population, as exemplified by the 60% suffering from arthritis and the 17% suffering from neurological disorders other than dementia
— id: 34303, year: 1995, vol: 43, page: 974, stat: Journal Article,

Contractures and loss of function in patients with Alzheimer's disease
Souren LE; Franssen EH; Reisberg B
1995 Jun;43(6):650-655, Journal of the American Geriatrics Society
OBJECTIVE: To investigate the prevalence of contractures in patients with Alzheimer's disease and to assess possible associations between contractures and cognitive and functional decline in Alzheimer's disease. DESIGN: Case series. SETTING: Subjects from an outpatient, university-based, dementia research center, followed, when necessary, into residential home and nursing home settings. PATIENTS: A consecutive sample of 161 patients (48 men, 113 women; mean age 75.3 +/- 8.6 years) with a clinical diagnosis of probable Alzheimer's disease and with deficits in basic activities of daily living or more severe functional impairment. MAIN OUTCOME MEASURES: For cognition, the Mini-Mental State Examination (MMSE); for functioning, the Functional Assessment Staging Scale (FAST); contracture is defined as a decrease of 50% or more of the normal passive range of motion of the joint. RESULTS: Prevalence of contractures was correlated highly with degree of functional impairment (r = .70, P < .001). More than three quarters of patients who had lost the ability to walk manifested contractures; however, contractures were found in fewer than 11% of all ambulatory patients examined. When present, contractures involved more than one extremity in 97% of cases and involved all four extremities in more than two-thirds of patients. CONCLUSION: Joint contractures are very common in the severe stages of Alzheimer's disease. More than a quarter of a million institutionalized residents in US nursing homes are likely to be afflicted by this potentially painful and disfiguring condition. Possible pathophysiology and contributing factors and possible means of intervention for this major source of disability are discussed
— id: 12768, year: 1995, vol: 43, page: 650, stat: Journal Article,

CEREBELLAR ATROPHY AND BETA-AMYLOIDOSIS IN AD
WEGIEL, J; WISNIEWSKI, HM; DZIEWIATKOWSKI, J; BADMAJEW, E; TAMAWSKI, M; REISBERG, B; MLODZIK, B; DELEON, M; MILLER, DC
1995 MAY ;54(3):428-428, Journal of neuropathology & experimental neurology
— id: 87305, year: 1995, vol: 54, page: 428, stat: Journal Article,

The neglected half of Alzheimer disease: cognitive and functional concomitants of severe dementia
Auer SR; Sclan SG; Yaffee RA; Reisberg B
1994 Dec;42(12):1266-1272, Journal of the American Geriatrics Society
OBJECTIVE: Traditional mental status and psychometric assessments bottom out in the late stages of Alzheimer disease (AD). A method adapted from cognitive testing in infants, the Ordinal Scales of Psychological Development was modified (M-OSPD) and applied to a severely demented population. The concurrent validity of this method was tested in comparison with Functional Assessment Staging (FAST). Internal consistency as a measure for reliability was also determined. DESIGN: Cross sectional study. SETTING: Subjects were generally evaluated in their residence, usually a nursing home or a private home. PATIENTS: Severely cognitively impaired subjects who fulfilled criteria for probable AD were studied. MEASUREMENTS: Evaluation consisted of clinical global, mental status, functional, and cognitive assessments including the Global Deterioration Scale (GDS) and the Mini-Mental State Examination (MMSE). RESULTS: Seventy patients were evaluated. Traditional mental status assessments (eg, the MMSE) manifested virtually uniform bottom scores in all GDS stage 7 subjects (n = 46), and GDS stage 6 subjects had MMSE scores within one standard deviation unit of zero. In contrast, the M-OSPD scale continued to show results in the last stages of the disease. The Spearman correlation coefficient between the M-OSPD total score and the 11 FAST substages represented in this sample was -0.77 (P < 0.001). CONCLUSIONS: The results indicate that patients who are functionally more impaired also show continuing increments in cognitive loss. These cognitive and functional assessments for measuring the magnitude of deterioration in AD can be applied to the estimated half-million nursing home residents presently labeled 'untestable' with the goal of optimization of care and residual capacities
— id: 6570, year: 1994, vol: 42, page: 1266, stat: Journal Article,

Quantitative EEG correlates of cognitive deterioration in the elderly [published erratum appears in Neurobiol Aging 1994 May-Jun;15(3):391]
Prichep LS; John ER; Ferris SH; Reisberg B; Almas M; Alper K; Cancro R
1994 Jan-Feb;15(1):85-90, Neurobiology of aging
We report on the quantitative analysis of the EEG (QEEG), using the Neurometric method, in large samples of normal elderly; normal subjectively impaired elderly; patients with mild cognitive impairment; patients presenting with a continuum of primary cognitive deterioration from mild to moderately severe as measured by the Global Deterioration Scale (GDS), compatible with dementia of the Alzheimer's type (DAT). Neurometric QEEG measures were found to be a sensitive index of degree of cognitive impairment, especially reflected in increased absolute and relative power in the theta band, with delta increasing in later stages of deterioration. While these abnormalities were widespread, neither localized or lateralized, MANOVA's for GDS and relative power in theta reached highest significance in a bilateral temporo-parietal arc. A possible relationship between hippocampal dysfunction, cognitive deterioration, and theta abnormalities is discussed in relation to these findings. The results suggest that Neurometric QEEG features are sensitive to the earliest presence of subjective cognitive dysfunction and might be useful in the initial evaluation of patients with suspected dementia, as well as in estimating the degree of cognitive deterioration in DAT patients
— id: 6488, year: 1994, vol: 15, page: 85, stat: Journal Article,

QEEG PREDICTION OF COGNITIVE DETERIORATION IN NORMAL ELDERLY
PRICHEP, LS; JOHN, ER; REISBERG, B; FERRIS, S
1994 NOV ;18(2):140-141, International journal of psychophysiology
— id: 87448, year: 1994, vol: 18, page: 140, stat: Journal Article,

The 1993 research awards in psychogeriatrics
Reisberg B
1994 Spring;6(1):7-11, International psychogeriatrics
— id: 13023, year: 1994, vol: 6, page: 7, stat: Journal Article,

Dementia staging in chronic care populations
Reisberg B; Sclan SG; Franssen E; Kluger A; Ferris S
1994 ;8 Suppl 1:S188-S205, Alzheimer disease & associated disorders
— id: 13022, year: 1994, vol: 8 Suppl 1, page: S188, stat: Journal Article,

A longitudinal study of cognitive function in elderly persons with subjective memory complaints
Flicker C; Ferris SH; Reisberg B
1993 Oct;41(10):1029-1032, Journal of the American Geriatrics Society
OBJECTIVE: To assess change in cognitive function in elderly individuals with subjective memory loss over a follow-up interval of more than 3 years. DESIGN: Prospective cohort study. SETTING: An outpatient research clinic in aging and dementia at a university hospital. PARTICIPANTS: A convenience sample of 59 healthy, elderly individuals (mean age 68.7 years) with memory complaints but no clinically apparent cognitive dysfunction. MEASUREMENTS: Participants were given a full diagnostic evaluation and were administered a neuropsychological test battery at baseline and follow-up. The cognitive assessment battery included 12 tests of recent memory, immediate memory, language function, visuospatial praxis, and psychomotor speed. Most of the tests had been established to be sensitive to cross-sectional age differences. RESULTS: Of 59 subjects, 54 (91.5%) were successfully followed up an average of 3.4 years later. Between baseline and follow-up, two tests exhibited significant improvement, two tests exhibited significant decline, and the other eight were unaffected. CONCLUSION: Elderly individuals with subjective perceptions of cognitive decrements who fail to provide clear evidence of cognitive impairment upon clinical interview are not at high risk for progressive cognitive deterioration over the subsequent 3- to 4-year interval
— id: 6370, year: 1993, vol: 41, page: 1029, stat: Journal Article,

A two-year longitudinal study of cognitive function in normal aging and Alzheimer's disease
Flicker C; Ferris SH; Reisberg B
1993 Apr-Jun;6(2):84-96, Journal of geriatric psychiatry & neurology
A group of 136 elderly subjects were administered a comprehensive neuropsychological test battery, which was readministered 2 years later. Among the 136 elderly subjects, 86 were assigned a diagnosis of probable Alzheimer's disease. An additional 33 young subjects were administered the assessment battery at baseline only. The normal elderly group exhibited no decline in cognitive test performance over the 2-year follow-up interval. Subjects with mild cognitive impairment, however, were as likely to deteriorate between baseline and follow-up as the more severely impaired subjects. The tests that exhibited longitudinal decline in the Alzheimer's disease patients constituted a subset of the tests that revealed cross-sectional deficits relative to the normal elderly. Differences in baseline cognitive test performance and in rate of cognitive deterioration were examined in relatively young versus relatively old Alzheimer's disease patients. Potential psychometric predictors of cognitive decline in the normal elderly were identified
— id: 6371, year: 1993, vol: 6, page: 84, stat: Journal Article,

The neurologic syndrome of severe Alzheimer's disease. Relationship to functional decline
Franssen EH; Kluger A; Torossian CL; Reisberg B
1993 Oct;50(10):1029-1039, Archives of neurology
OBJECTIVE--To assess the possible association between functional decline and noncognitive neurologic signs in the severe stages of Alzheimer's disease (AD). DESIGN--Case series. SETTING--Subjects from a dementia research referral center, longitudinally followed, when necessary, into residential home and nursing home settings. PATIENTS--A consecutive sample of 56 patients (16 men, 40 women; mean age, 74.6 years) with a clinical diagnosis of probable AD in the moderately severe and severe stages. MAIN OUTCOME MEASURE--For global dementia severity, the Global Deterioration Scale and Mini-Mental State examination; for functional assessment, the Functional Assessment Staging Scale; and for assessment of neurologic function, nine release signs (primitive reflexes), 10 measures of extrapyramidal function, and five measures of pyramidal function, including deep-tendon reflexes and plantar signs. Changes in activity or presence of neurologic signs were rated on a seven-point scale. Results were analyzed in terms of prevalence and magnitude of change in relation to functional impairment. RESULTS--Prevalence and mean scores of certain release signs, certain extrapyramidal measures commonly referred to as bradykinesia, and certain pyramidal signs showed significant associations with the magnitude of functional impairment. Other neurologic measures, for example, the palmomental reflex, and certain extrapyramidal measures commonly seen in Parkinson's disease, including the glabellar blink reflex, cogwheeling, tremor, shuffling gait, and festination, did not show significant increments with continuing functional decline in AD. CONCLUSIONS--Functional decline in the advanced stages of AD appears to be associated with a particular combination of progressive cortical, extrapyramidal, and pyramidal system dysfunction. The characteristics of this neurologic syndrome of the severe stages of AD differ from those of other neurologic disorders. For example, the pattern of extrapyramidal system disease is different from that seen in Parkinson's disease. The neurologic syndrome of the severe stages of AD is amenable to description and deserves further investigation
— id: 6372, year: 1993, vol: 50, page: 1029, stat: Journal Article,

Milacemide: a placebo-controlled study in senile dementia of the Alzheimer type
Dysken MW; Mendels J; LeWitt P; Reisberg B; Pomara N; Wood J; Skare S; Fakouhi JD; Herting RL
1992 May;40(5):503-506, Journal of the American Geriatrics Society
OBJECTIVE: Milacemide, a MAO-B inhibitor that is also a prodrug for glycine, was tested as a treatment for senile dementia of the Alzheimer type (SDAT) because of its potential for enhancing cognition in animal models of impaired learning and memory. DESIGN: Double-blind, placebo-controlled, randomized clinical trial. SETTING: Sixteen study sites, both university-affiliated and private. PATIENTS: A total of 228 outpatients (116 men and 112 women) with SDAT, ranging in age from 49-93 years. INTERVENTION: 1200 mg/day milacemide treatment for 1 month (113 patients received milacemide, and 115 patients received placebo). MAIN OUTCOME MEASURES: Alzheimer's Disease Assessment Scale and the Mini-Mental State Examination. RESULTS: Milacemide-treated SDAT patients did not show significant improvement in any of the outcome measures used. Significant elevations in liver enzymes in four subjects were of sufficient magnitude to necessitate withdrawal from the study. CONCLUSIONS: Milacemide does not appear to be an effective treatment in enhancing cognition in SDAT patients
— id: 23692, year: 1992, vol: 40, page: 503, stat: Journal Article,

The 1991 IPA Research Awards in Psychogeriatrics
Reisberg B
1992 ;4 Suppl 2:141-146, International psychogeriatrics
— id: 13810, year: 1992, vol: 4 Suppl 2, page: 141, stat: Journal Article,

Pharmacologic treatment of Alzheimer's disease: a methodologic critique based upon current knowledge of symptomatology and relevance for drug trials
Reisberg B; Ferris SH; Torossian C; Kluger A; Monteiro I
1992 ;4 Suppl 1:9-42, International psychogeriatrics
Research on the nature of clinical symptomatology in AD indicates that two fundamentally different types of symptoms are identifiable. Symptoms within each of these two domains have common characteristics. The first symptomatic domain has been termed the 'cognitive domain' and the second the 'noncognitive behavioral domain.' Symptoms and losses in the cognitive domain occur invariably and progressively with the advance of AD over time. Symptoms in the behavioral domain do not invariably occur in AD and do not progress monotonically with the advance in AD over time. However, characteristic behavioral domain symptoms can be described over the course of AD. The two symptomatic domains are likely to differ not only in nature and progression in AD, but also in underlying pathophysiology and in terms of possible treatment modalities. They also pose fundamentally different issues of assessment in AD. These distinct factors necessitate the separate assessment of the two symptomatic domains in AD treatment trials. Judgments of efficacy and utility in remediating either symptomatic domain in AD should take into consideration the effects of treatment on both cognitive domain and behavioral domain symptoms separately and interactively. Appropriate assessment procedures are discussed
— id: 13764, year: 1992, vol: 4 Suppl 1, page: 9, stat: Journal Article,

Alzheimer's disease--clinical course: methodologic implications for pharmacologic trials
Reisberg B; Oppenheim G
1992 ;4 Suppl 1(5):5-7, International psychogeriatrics
— id: 34304, year: 1992, vol: 4 Suppl 1, page: 5, stat: Journal Article,

Dementia of the Alzheimer type recapitulates ontogeny inversely on specific ordinal and temporal parameters
Reisberg, Barry; Pattschull-Furlan, Angela; Franssen, Emile; Sclan, Steven G; Kluger, Alan; Dingcong, Louis; Ferris, Steven H
Neurodevelopment, aging and cognition Cambridge, MA, US: Birkhauser, 1992,
(from the chapter) it is reasonable at this time to speculate that the course of AD [Alzheimer's disease] may result directly or indirectly from the disruption of CNS developmental factors /// global and hierarchic descriptions of clinical changes in AD / concordant ordinal (hierarchic) description of changes in AD / degenerative course of AD: developmental homologies / a utilitarian implication of the homologous relationship between normal human development and AD: development of improved psychological assessment of AD / possible etiologic implications of the degenerative course of AD
— id: 4797, year: 1992, vol: , page: 345, stat: Chapter,

Functional assessment staging (FAST) in Alzheimer's disease: reliability, validity, and ordinality
Sclan SG; Reisberg B
1992 ;4 Suppl 1:55-69, International psychogeriatrics
Evaluation of changes in functional performance and activities of daily living skills is an essential aspect of the assessment of elderly individuals with chronic illness. Although functional decrement is a central aspect of Alzheimer's disease (AD), many measures currently utilized to assess these changes have limitations. Empirical and systematic examination of the functional changes occurring in patients with AD has resulted in the development of an assessment measure termed Functional Assessment Staging (FAST) that allows for the specific evaluation of these changes throughout the entire course of AD. In this paper the results of three separate investigations regarding the reliability, validity, and progressive ordinality of FAST are described. The results indicate that FAST is a reliable and valid assessment technique for evaluating functional deterioration in AD patients throughout the entire course of the illness. Moreover, the results suggest that the FAST elucidates a characteristic pattern of progressive, ordinal, and functional decline in AD. Because the elements of functional capacity incorporated in FAST are relatively universal and readily ascertainable, as well as characteristic of the course of AD, FAST can serve as a strong diagnostic and differential diagnostic aid for clinicians. The sensitivity of FAST to the entire course of AD, even in its most severe stages, may be indicative of the potential value of this instrument for further investigation of the temporal longitudinal course of AD, and of the relationships between clinical pathology and neuropathology throughout the entire longitudinal course of AD
— id: 13765, year: 1992, vol: 4 Suppl 1, page: 55, stat: Journal Article,

Topography of cross-sectional and longitudinal glucose metabolic deficits in Alzheimer's disease. Pathophysiologic implications
Smith GS; de Leon MJ; George AE; Kluger A; Volkow ND; McRae T; Golomb J; Ferris SH; Reisberg B; Ciaravino J; et al
1992 Nov;49(11):1142-1150, Archives of neurology
Positron emission tomographic studies of cerebral glucose metabolism have shown high diagnostic specificity in distinguishing among the degenerative dementias and differentiating between Alzheimer's disease (AD) and normal aging. The current investigation was undertaken to characterize the regional glucose metabolic deficits in AD, using cross-sectional and longitudinal study designs. All subjects met the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD (n = 45) or were normal (n = 20), and the AD subjects were subdivided into incipient and mild AD and moderate plus moderately severe subgroups based on the Global Deterioration Scale. The subjects underwent a non-contrast computed tomographic scan and a positron emission tomographic (PETT VI) scan. The AD subjects (n = 14) and normal control subjects (n = 15) received evaluations 2 to 3 years after baseline study. The brain regions that show glucose metabolic deficits cross-sectionally (temporal and parietal association areas, with lesser degrees of deficit in subcortical gray matter structures), over the stages of AD, also show further deficits longitudinally within the same AD subjects. The reduction in glucose metabolism is greater than would be expected from the degree of brain atrophy. The glucose metabolic deficits are discussed in the context of neuropathologic findings and neurotransmitter deficits in AD
— id: 9459, year: 1992, vol: 49, page: 1142, stat: Journal Article,

Management of behavior disturbance in Alzheimer disease: current knowledge and future directions
Teri L; Rabins P; Whitehouse P; Berg L; Reisberg B; Sunderland T; Eichelman B; Phelps C
1992 Summer;6(2):77-88, Alzheimer disease & associated disorders
Assessment and treatment of behavior problems in patients with Alzheimer disease and related disorders is a seriously neglected area of study. Despite the fact that such problems are integral to the disorder, little is known about effective management. This article summarizes the current thinking on five areas of prime importance to patients, care providers, and health care professionals: agitation, assault/aggression, screaming, wandering, and depression/apathy/withdrawal. Methodological guidelines for studying these disorders are provided. Emphasis is on recognizing that behavior problems are important areas of study in their own right as well as in conjunction with studies of cognition
— id: 34305, year: 1992, vol: 6, page: 77, stat: Journal Article,

Mild cognitive impairment in the elderly: predictors of dementia
Flicker C; Ferris SH; Reisberg B
1991 Jul;41(7):1006-1009, Neurology
We conducted full diagnostic evaluations, including a comprehensive cognitive assessment battery, of a group of 32 elderly subjects with a clinically identified mild cognitive impairment and a group of 32 age-matched and education-matched normal subjects. The mildly impaired subjects performed significantly more poorly than the controls on tests of recent memory, remote memory, language function, concept formation, and visuospatial praxis. Follow-up evaluations of cognitive status 2 years later revealed clinically detectable cognitive decline relative baseline in 23 (72%) of the mildly impaired subjects. Several of the objective psychological tests accurately discriminated at baseline between the decliners and nondecliners in the mildly impaired group. Among the 20 mildly impaired subjects with no complicating conditions, 16 exhibited cognitive deterioration between baseline and follow-up. These results suggest that most elderly subjects with mild cognitive deficits, as determined by clinical evaluation and objective psychological testing, will manifest the progressive mental deterioration characteristic of dementia and that psychometric predictors can be used to distinguish between benign and more significant underlying disorders in mildly impaired elderly subjects
— id: 13965, year: 1991, vol: 41, page: 1006, stat: Journal Article,

Cognition-independent neurologic symptoms in normal aging and probable Alzheimer's disease
Franssen EH; Reisberg B; Kluger A; Sinaiko E; Boja C
1991 Feb;48(2):148-154, Archives of neurology
Deep tendon reflexes, plantar responses, muscle tone, and release signs were studied as 14 individual clinical variables and as five summary variables in 135 aged subjects, including 27 control subjects, 20 subjects with mild cognitive impairment, and 88 subjects with successive stages of probable Alzheimer's disease. Changes in activity of elicited responses were rated on a seven-point scale. Results were analyzed both as prevalence and mean degree of change in activity. Rating on a variable combining all 14 individual variables was significantly higher in a group with mild cognitive impairment than in a control group. Subjects with an early stage of Alzheimer's disease had both higher prevalence of increased activity and increased mean scores of deep tendon reflexes and muscle tone. They had a higher prevalence of increased activity on a variable combining three release signs. Patients with a late stage of Alzheimer's disease had significantly increased prevalence and mean scores of muscle tone and grasping and sucking reflexes compared with control subjects and patients with the early stage of Alzheimer's disease
— id: 14137, year: 1991, vol: 48, page: 148, stat: Journal Article,

CLINICAL MARKERS OF EARLY ALZHEIMERS-DISEASE
Ferris, SH; Flicker, C; Reisberg, B; Deleon, MJ
1990 May-Jun;11(3):256-256, Neurobiology of aging
— id: 31938, year: 1990, vol: 11, page: 256, stat: Journal Article,

Alzheimer disease: the clinical syndrome; diagnostic and etiologic importance
Reisberg B
1990 ;129(4):2-4, Acta neurologica Scandinavica. Supplementum
— id: 34306, year: 1990, vol: 129, page: 2, stat: Journal Article,

THE CLINICAL COURSE OF ALZHEIMERS-DISEASE
Reisberg, B; Franssen, E; Kluger, A; Sclan, S; Shulman, E; Steinberg, G; Deleon, MJ; Ferris, SH
1990 May-Jun;11(3):253-253, Neurobiology of aging
— id: 31937, year: 1990, vol: 11, page: 253, stat: Journal Article,

Application of Piagetian measures of cognition in severe Alzheimer's disease
Sclan SG; Foster JR; Reisberg B; Franssen E; Welkowitz J
1990 Nov;15(4):221-226, Psychiatric journal of the University of Ottawa
Conventional psychometric measures uniformly yield zero or near zero scores (i.e., 'bottom-out') as patients with Alzheimer's disease (AD) progress to the more severe stages of the illness. Consequently, there are no psychometric measures which objectively assess the mental abilities of AD patients with very severe cognitive impairment. We explored the hypothesis that mental function in AD patients with very severe cognitive impairment can be effectively assessed using test measures developed to assess the earliest stage of cognitive development as proposed by Piaget. We also investigated the relationship between decline on these experimental cognitive measures and progressive functional disability in patients with severe cognitive impairment. The results indicate that modified instruments derived from measures developed to assess Piaget's sensorimotor stage of cognitive development provide useful information about the cognitive abilities of very severely impaired AD patients. These modified instruments provide a measure of cognition in these extremely impaired patients that has acceptable validity and demonstrable reliability
— id: 14280, year: 1990, vol: 15, page: 221, stat: Journal Article,

Diagnosis and treatment of senile dementia
Bergener, Manfred; Reisberg, Barry
Berlin ; New York : Springer-Verlag, c1989,
— id: 254, year: 1989, vol: , page: , stat: ,

Alzheimer's disease: longitudinal CT studies of ventricular change
de Leon MJ; George AE; Reisberg B; Ferris SH; Kluger A; Stylopoulos LA; Miller JD; La Regina ME; Chen C; Cohen J
1989 Jun;152(6):1257-1262, American journal of roentgenology
A 3-year longitudinal study was conducted with 50 Alzheimer's disease patients and 45 elderly control subjects. All study participants received an extensive evaluation that included brain CT at baseline and follow-up. Quantitation of ventricular size, using both linear and volume methods, revealed highly significant cross-sectional and longitudinal differences between the Alzheimer patients and control subjects. Specifically, the annual rate of change in ventricular volume was approximately 9% in the Alzheimer patients and approximately 2% in the controls. The presence of age-related white matter lesions had no effect on the clinical course of the patients or on the changes in ventricular size. Among the Alzheimer patients, the rate of clinical decline was strongly related to the rate of change in ventricular size. Baseline ventricular measurements were of no value in predicting the subsequent rate of clinical deterioration or ventricular enlargement. The results suggest that changes in ventricular size closely reflect the clinical changes in Alzheimer patients
— id: 9464, year: 1989, vol: 152, page: 1257, stat: Journal Article,

ALZHEIMERS-DISEASE - LONGITUDINAL CT STUDIES OF VENTRICULAR CHANGE
Deleon, MJ; George, AE; Reisberg, B; Ferris, SH; Kluger, A; Stylopoulos, LA; Miller, JD; Laregina, ME; Chen, C; Cohen, J
1989 Mar-Apr;10(2):371-376, AJNR. American journal of neuroradiology
— id: 31644, year: 1989, vol: 10, page: 371, stat: Journal Article,

The effects of mood changes and antidepressants on the cognitive capacity of elderly depressed patients [see comments]
Georgotas A; McCue RE; Reisberg B; Ferris SH; Nagachandran N; Chang I; Mir P
1989 Fall;1(2):135-143, International psychogeriatrics
Seventy-eight nondemented elderly depressed patients underwent an extensive battery of cognitive tests both before and after seven weeks of treatment with nortriptyline, phenelzine, or placebo. Clinical and cognitive evaluations of the patients were under double-blind conditions. Response to treatment did not appear to significantly affect cognitive capacity; neither did treatment with an active substance as compared to placebo. In addition, the baseline level of cognitive functioning did not appear related to whether a patient responded to treatment. The authors conclude that under optimal conditions neither antidepressant produces measurable changes in the cognitive capacity of nondemented elderly patients
— id: 10849, year: 1989, vol: 1, page: 135, stat: Journal Article,

Beta-amyloid protein probe hybridized to chromosome 9 in 3 Alzheimer disease individuals
Jenkins EC; Devine-Gage EA; Yao XL; Houck GE Jr; Brown WT; Robakis NK; Wisniewski KE; Silverman WP; Reisberg B; Wisniewski HM
1989 ;317(6):269-275, Progress in clinical & biological research
We have reported recently the sublocalization of an Alzheimer Disease-associated gene that encodes for cerebrovascular beta-amyloid protein (BAP). Its locus appears to be at or proximal to band 21q2105 through band 21q11.1. We have also observed hybridization to chromosome 20 in normal and Down syndrome individuals using the single-stranded form of the probe. Further, we have found that BAP hybridizes to chromosome 9 in lymphoblastoid cells from three individuals from two families with familial Alzheimer Disease (AD). We have now obtained additional data which shows significant hybridization to chromosomes 9,20 and 21 for two normal control individuals, a Down syndrome (DS) individual and three AD individuals. When the normal and Down Syndrome individuals were compared to the group of individuals with AD, significant hybridization to chromosome 9 occurred in the Alzheimer group only (p less than .05). Almost half of the silver grains on chromosome 9 in the three AD individuals were localized to the distal area of the long arm. Whether these observations demonstrate an apparent genetic marker in these three individuals with familial AD, or whether our observations have identified a marker for both familial and sporadic AD will be determined by further studies
— id: 34307, year: 1989, vol: 317, page: 269, stat: Journal Article,

The stage specific temporal course of Alzheimer's disease: functional and behavioral concomitants based upon cross-sectional and longitudinal observation
Reisberg B; Ferris SH; de Leon MJ; Kluger A; Franssen E; Borenstein J; Alba RC
1989 ;317:23-41, Progress in clinical & biological research
A series of studies published over the past 6 years now permit a relatively precise description of the temporal course of Alzheimer's disease (AD). Initially, 7 global stages of CNS aging and AD were described. Subsequently, data on the stage specific relationship between these stages and widely employed mental status, psychometric, and other assessment measures were collected. Longitudinal studies helped to clarify the borders between normal CNS aging and AD using these measures. Other studies described functioning and self-care correlates of the 7 global stages. These were ultimately divisible into 16 clearly defined, ordinal functional stages. Empirical longitudinal observations permitted the description of the mean temporal course of each of the 16 functional stages of aging and AD. The cross-sectional stage specific data on mental status and other measures can now be applied to the mean temporal course observations and the validity of the temporal estimates forwarded can be investigated in detail. Etiologic hypotheses based upon the observed phenomenologic and temporal course of AD are discussed
— id: 9465, year: 1989, vol: 317, page: 23, stat: Journal Article,

Clinical features of a neuropathologically verified familial Alzheimer's cohort with onset in the fourth decade: comparison with senile onset Alzheimer's disease and etiopathogenic implications
Reisberg B; Ferris SH; Franssen E; Jenkins EC; Wisniewski KE
1989 ;317:43-54, Progress in clinical & biological research
Clinical and pathologic features of a family with early onset, autosomal dominant, familial Alzheimer's disease (AD) are compared and contrasted with senile onset dementia of the Alzheimer type. Late onset AD has previously been observed to have a characteristic progression and clinical course. A previously unreported pedigree, with two siblings and their father affected, of early clinical onset is presented. Molecular genetic study of this family using in situ chromosome hybridization showed an apparent marker on chromosome 9. This early onset form of AD is observed to be clinically consistent with the common late onset form of AD, but follows a more rapid course. An etiopathogenic model explaining the early onset, and other forms of AD is presented
— id: 10782, year: 1989, vol: 317, page: 43, stat: Journal Article,

NYU computerized test battery for assessing cognition in aging and dementia
Ferris SH; Flicker C; Reisberg B
1988 ;24(4):699-702, Psychopharmacology bulletin
— id: 18811, year: 1988, vol: 24, page: 699, stat: Journal Article,

Equivalent spatial-rotation deficits in normal aging and Alzheimer's disease
Flicker C; Ferris SH; Crook T; Reisberg B; Bartus RT
1988 Aug;10(4):387-399, Journal of clinical & experimental neuropsychology (Netherlands)
Two tests of spatial-rotation ability were administered to 17 young normals, 23 aged normals, and 51 patients with diagnoses of Alzheimer's disease (AD). The AD patients consisted of 28 early dementia patients and 23 advanced dementia patients. On a computerized version of the Boston Naming Test, 40 objects were presented for naming, 20 of which were rotated 180 degrees. The subjects' capacity for mental rotation was assessed on the basis of their accuracy of naming of rotated vs. unrotated objects. On Money's Standardized Road Map Test, in which the subject is asked whether turns on a map are to the left or to the right, spatial-rotation ability was assessed on the basis of the subject's left-right orientation on turns with movement away from the subject (requiring no rotation) vs. turns with movement toward the subject (requiring rotation). Performance on both tasks was progressively worse in the young normal, aged normal, early dementia, and advanced dementia groups. Both tasks demonstrated a clear spatial-rotation deficit in the elderly. Although the spatial-rotation effect was superimposed upon deficits in naming and left-right orientation in the demented subjects, the magnitude of the rotation effect did not significantly differ in the aged normal vs. the early dementia group on either task, suggesting that early AD produces no further impairment of spatial-rotation abilities than is produced by normal aging
— id: 10993, year: 1988, vol: 10, page: 387, stat: Journal Article,

IMMUNE DYSFUNCTIONS - NEW TARGETS OF DRUG DISCOVERY FOR ALZHEIMERS-DISEASE AND OTHER COGNITIVE DISORDERS
Lal, H; Forster, MJ; Retz, KC; Reisberg, B
1988 Jan;15(2-3):95-99, Drug development research
— id: 31781, year: 1988, vol: 15, page: 95, stat: Journal Article,

A curriculum for education in geriatric psychiatry
Marin RS; Foster JR; Ford CV; Reifler BV; Reisberg B; Robinowitz CB; Sledge WH; Spar J; Tighe PJ
1988 Jul;145(7):836-843, American journal of psychiatry
The authors present recommendations for educating medical students and psychiatric residents in geropsychiatry. They are primarily concerned with the objectives and methods rather than the content of training. Proposals are structured in terms of training objectives and educational settings in which such training takes place. The proposals are intended to be specific enough to be truly useful and at the same time sufficiently generalizable to adapt to geropsychiatric training in a variety of institutions. Priority is given to integrating knowledge of normal and abnormal aging with the clinical skills and empathy necessary to approach patients with competence and understanding
— id: 34308, year: 1988, vol: 145, page: 836, stat: Journal Article,

Functional assessment staging (FAST)
Reisberg B
1988 ;24(4):653-659, Psychopharmacology bulletin
— id: 34309, year: 1988, vol: 24, page: 653, stat: Journal Article,

Brief Cognitive Rating Scale (BCRS)
Reisberg B; Ferris SH
1988 ;24(4):629-636, Psychopharmacology bulletin
— id: 18810, year: 1988, vol: 24, page: 629, stat: Journal Article,

Global Deterioration Scale (GDS)
Reisberg B; Ferris SH; de Leon MJ; Crook T
1988 ;24(4):661-663, Psychopharmacology bulletin
— id: 9472, year: 1988, vol: 24, page: 661, stat: Journal Article,

STAGE-SPECIFIC BEHAVIORAL, COGNITIVE, AND INVIVO CHANGES IN COMMUNITY RESIDING SUBJECTS WITH AGE-ASSOCIATED MEMORY IMPAIRMENT AND PRIMARY DEGENERATIVE DEMENTIA OF THE ALZHEIMER TYPE
Reisberg, B; Ferris, SH; Deleon, MJ; Sinaiko, E; Franssen, E; Kluger, A; Mir, P; Borenstein, J; George, AE; Shulman, E; Steinberg, G; Cohen, J
1988 Nov 30;15(2-3):101-114, Drug development research
— id: 31654, year: 1988, vol: 15, page: 101, stat: Journal Article,

Institutionalization of Alzheimer's disease patients: reducing precipitating factors through family counseling
Ferris SH; Steinberg G; Shulman E; Kahn R; Reisberg B
1987 Spring;8(1):23-51, Home health care services quarterly
Although home-care of Alzheimer's disease (AD) patients is more cost-effective than institutionalization, there is limited knowledge concerning the causes and prevention of institutionalization. The goal of this project was to determine the circumstances related to institutionalization of AD patients and to determine if a family counseling program can reduce these precipitating factors. In Study 1, we surveyed 109 family members of institutionalized AD patients. Primary precipitating factors included difficulties with patient behavior, insufficient auxiliary help and respite, financial difficulties, and caregiver emotional and physical complaints. In Study 2 we evaluated the effectiveness of an enhanced counseling program which included specific intervention techniques to cope with precipitating factors. For 41 AD family members who were seriously contemplating institutionalization, the precipitating factors prior to counseling were similar to those found in Study 1. After six months of individual counseling, home visits, and participation in caregiver support groups, there was only one placement, and a consistent reduction in the precipitating factors. These preliminary results suggest that a specially designed counseling program may delay or forestall institutionalization
— id: 18809, year: 1987, vol: 8, page: 23, stat: Journal Article,

Abnormal temporal lobe response in Alzheimer's disease during cognitive processing as measured by 11C-2-deoxy-D-glucose and PET
Miller JD; de Leon MJ; Ferris SH; Kluger A; George AE; Reisberg B; Sachs HJ; Wolf AP
1987 Apr;7(2):248-251, Journal of cerebral blood flow & metabolism
Elderly controls and probable Alzheimer's disease patients underwent serial positron emission tomography (PET) studies during a baseline condition and while performing a verbal memory task. For the temporal lobes, all 7 Alzheimer patients demonstrated a relative shift in glucose metabolic rates to the right hemisphere during the memory condition relative to baseline, and 5 of 7 controls showed a shift to the left hemisphere. Baseline absolute regional metabolic rates replicate previous findings and were somewhat less useful than the memory challenge in differentiating patients from controls. These results indicate that a temporal lobe abnormality in Alzheimer's disease is related to memory performance.
— id: 9474, year: 1987, vol: 7, page: 248, stat: Journal Article,

Behavioral symptoms in Alzheimer's disease: phenomenology and treatment
Reisberg B; Borenstein J; Salob SP; Ferris SH; Franssen E; Georgotas A
1987 May;48 Suppl(2):9-15, Journal of clinical psychiatry
Limited information is available regarding the incidence, nature, and treatment of behavioral problems in Alzheimer's disease (AD). A chart review of 57 outpatients with a diagnosis of AD was conducted to examine these issues. Thirty-three (58%) patients had significant behavioral symptomatology (most commonly delusions, nonspecific agitation, and diurnal rhythm disturbances). Twenty-seven were treated with thioridazine (10-250 mg/day), 15 (55.6%) of whom were judged to have a positive response (mean maximum dose = 55 mg/day). Information regarding the characteristic phenomenology of the behavioral symptoms studied was used to design a clinical rating instrument for AD patients, the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD), which should be useful in prospective studies of behavioral symptoms as well as in pharmacologic trials
— id: 18155, year: 1987, vol: 48 Suppl, page: 9, stat: Journal Article,

CT AND PET STUDY OF LEUKOENCEPHALOPATHY IN ALZHEIMERS-DISEASE
Deleon, MJ; George, AE; Ferris, SH; Christman, DR; Fowler, J; Budzilovich, G; Miller, JD; Reisberg, B; Wolf, AP
1986 Dec;31(1-4):219-220, International journal of neuroscience
— id: 31292, year: 1986, vol: 31, page: 219, stat: Journal Article,

Dexamethasone suppression in dementia, depression, and normal aging
Georgotas A; McCue RE; Kim OM; Hapworth WE; Reisberg B; Stoll PM; Sinaiko E; Fanelli C; Stokes PE
1986 Apr;143(4):452-456, American journal of psychiatry
Dexamethasone suppression tests (DSTs) were performed for 18 moderately demented elderly patients, 66 depressed elderly outpatients, and 25 age- and sex-matched healthy elderly control subjects. Seventeen percent of the demented patients and 4% of the normal subjects were DST nonsuppressors, compared to 38% of the total depressed group. The postdexamethasone plasma cortisol levels of the dementia group fell between those of the normal and the depressed subjects. In addition, demented patients had postdexamethasone cortisol levels significantly lower than those of depressed patients with high Hamilton depression scores. Older subjects in all diagnostic categories, including normal subjects, had higher postdexamethasone plasma cortisol levels
— id: 22494, year: 1986, vol: 143, page: 452, stat: Journal Article,

Periventricular lucencies in the CT scans of aged and demented patients
London E; de Leon MJ; George AE; Englund E; Ferris S; Gentes C; Reisberg B
1986 Aug;21(10):960-962, Biological psychiatry
— id: 9475, year: 1986, vol: 21, page: 960, stat: Journal Article,

Dementia: a systematic approach to identifying reversible causes
Reisberg B
1986 Apr;41(4):30-46, Geriatrics
The development of FAST is of great importance to clinicians in identifying possibly remediable complications of Alzheimer's disease and distinguishing them from the characteristic progression of the illness. Premature loss of speech in an otherwise uncomplicated Alzheimer's-type presentation should lead the clinician to strongly suspect focal cerebral pathology, especially cerebral infarction
— id: 34310, year: 1986, vol: 41, page: 30, stat: Journal Article,

Remediable behavioral symptomatology in Alzheimer's disease
Reisberg B; Borenstein J; Franssen E; Shulman E; Steinberg G; Ferris SH
1986 Dec;37(12):1199-1201, Hospital & community psychiatry
— id: 18812, year: 1986, vol: 37, page: 1199, stat: Journal Article,

Longitudinal course of normal aging and progressive dementia of the Alzheimer's type: a prospective study of 106 subjects over a 3.6 year mean interval
Reisberg B; Ferris SH; Shulman E; Steinberg G; Buttinger C; Sinaiko E; Borenstein J; de Leon MJ; Cohen J
1986 ;10(3-5):571-578, Progress in neuro-psychopharmacology & biological psychiatry
Elderly, community residing subjects (N = 106; mean age = 70.6 +/- 6.02 years) with cognitive functioning consistent with normal aging or dementia of the Alzheimer's type (DAT), were followed over a 3.6 year mean interval (range = 2.78 to 5.12 years). All subjects were assessed at baseline on the Global Deterioration Scale (GDS), a global clinical instrument reflecting the continuum of cognitive dysfunction from normal aging to severe DAT. At follow-up subjects were reassessed with respect to mortality, institutionalization and clinical change, defined as at least a two-point change on the 7-point GDS. Our results suggest that patients at deterioration levels GDS greater than or equal to 4, are more likely to show negative outcomes, specifically, institutionalization (Ps less than .001), death (Ps less than .01), or, for the community residing remainder, clinical deterioration (Ps less than .05), than subjects from less impaired (GDS = 2 or GDS = 3) subject groups. Seventy-six per cent of subjects at deterioration levels four or greater (N = 34) had negative outcomes at follow-up, whereas ninety percent of subjects with deterioration levels less than four (N = 72) did not.
— id: 9479, year: 1986, vol: 10, page: 571, stat: Journal Article,

REVERSAL OF NORMAL DEVELOPMENTAL FUNCTIONAL STAGES IN ALZHEIMERS-DISEASE - IMPLICATIONS WITH RESPECT TO ETIOLOGY, DIAGNOSIS AND TREATMENT
Reisberg, B; Ferris, SH; Franssen, E
1986 Dec;31(1-4):220-220, International journal of neuroscience
— id: 31293, year: 1986, vol: 31, page: 220, stat: Journal Article,

CT AND PET STUDY OF LEUKOENCEPHALOPATHY IN ALZHEIMERS-DISEASE
Deleon, MJ; George, AE; Ferris, SH; Gentes, CI; Christman, DR; Fowler, J; Budzilovich, G; London, E; Miller, JD; Reisberg, B; Wolf, AP
1985 ;6(3):468-468, AJNR. American journal of neuroradiology
— id: 30911, year: 1985, vol: 6, page: 468, stat: Journal Article,

OCCUPATIONAL-THERAPY INTERVENTION WITH ALZHEIMERS-DISEASE PATIENTS
Rabinowitz, E; Reisberg, B
1985 ;25(10):172-172, Gastroenterologist
— id: 30832, year: 1985, vol: 25, page: 172, stat: Journal Article,

A clinical rating scale for symptoms of psychosis in Alzheimer's disease
Reisberg B; Ferris SH
1985 ;21(1):101-104, Psychopharmacology bulletin
— id: 18814, year: 1985, vol: 21, page: 101, stat: Journal Article,

An ordinal functional assessment tool for Alzheimer's-type dementia
Reisberg B; Ferris SH; Franssen E
1985 Jun;36(6):593-595, Hospital & community psychiatry
— id: 18813, year: 1985, vol: 36, page: 593, stat: Journal Article,

Positron emission tomography and computed tomography assessments of the aging human brain
de Leon MJ; George AE; Ferris SH; Christman DR; Fowler JS; Gentes CI; Brodie J; Reisberg B; Wolf AP
1984 Feb;8(1):88-94, Journal of computer assisted tomography
The relationship between alterations in brain structure and brain function was studied in vivo in both young and elderly human subjects. Computed tomography revealed significant age-related ventricular and cortical sulcal dilatation. The cortical changes were most closely related to age. Positron emission tomography failed to show regional changes in brain glucose metabolic rate. The results suggest that the normal aging brain undergoes structural atrophic changes without incurring regional metabolic changes. Examination of the correlations between the structural and the metabolic measures revealed no significant relationships. These data are discussed with respect to the significant structure-function relationships that have been reported in Alzheimer disease.
— id: 9482, year: 1984, vol: 8, page: 88, stat: Journal Article,

Sister chromatid exchanges and cell cycle kinetics in Alzheimer's disease
Fischman HK; Reisberg B; Albu P; Ferris SH; Rainer JD
1984 Mar;19(3):319-327, Biological psychiatry
Six female outpatients with Alzheimer's disease (AD) along with four female controls of a similar age range were analyzed for sister chromatid exchangers (SCEs), cell cycle kinetics, and sensitivity to mutagens, in lymphocyte cultures. The mean level of SCEs for the AD patients was 11.40 SCEs/metaphase, while that for the controls was 9.12. The difference between the two groups was significant as shown by the Wilcoxon rank-sum test (p = 0.05). Cell cycle was 50% longer both in the AD patients (31.7 hr) and aged controls (31.5 hr) than in normal young adults (21.76 hr). Mitomycin-C (MMC) decreased the mitotic index in AD patients by 35% and in controls by only 12%. MMC also increased the cell cycle duration in AD patients by a greater extent (20%) than it did in the controls (13.5%), and AD cells were more sensitive to the toxic effects of bromodeoxyuridine. What appeared to be chromosomes with prematurely divided centromeres were also observed in AD cells
— id: 18816, year: 1984, vol: 19, page: 319, stat: Journal Article,

Alzheimer's disease. Stages of cognitive decline
Reisberg B
1984 Feb;84(2):225-228, American journal of nursing
— id: 34311, year: 1984, vol: 84, page: 225, stat: Journal Article,

Familial nature of Alzheimer's disease?
Reisberg B; deLeon MJ; Ferris SH
1984 Nov 15;311(20):1318-1319, New England journal of medicine
— id: 18815, year: 1984, vol: 311, page: 1318, stat: Journal Article,

[Methodological problems in geriatric psychopharmacology]
Crook T; Ferris S; Reisberg B
1983 Dec 29;12(48):3132-3140, La presse medicale (1983)
— id: 18817, year: 1983, vol: 12, page: 3132, stat: Journal Article,

Positron emission tomographic studies of aging and Alzheimer disease
de Leon MJ; Ferris SH; George AE; Christman DR; Fowler JS; Gentes C; Reisberg B; Gee B; Emmerich M; Yonekura Y; Brodie J; Kricheff II; Wolf AP
1983 May-Jun;4(3):568-571, AJNR. American journal of neuroradiology
In this study the positron emission tomographic (PET)-18F-2-deoxy-2-fluoro-D-glucose (FDG) technique was used to study both normal aging and senile dementia. The results derived from 15 young normal subjects (mean age, 26 +/- 5 years) and 22 elderly normal subjects (mean age, 66 +/- 7 years) failed to indicate significant metabolic changes associated with age. A group of 24 patients with senile dementia (mean age, 73 +/- 7 years) showed consistent diminutions in regional glucose use relative to the elderly normals. Across all brain regions the diminutions were 17%-24%. There were also significant correlations between the measures of glucose use and the measures of cognitive functioning. Discriminant function classification analysis results indicate that better than 80% classification accuracy can be achieved for individual PET measures. These data suggest a possible future diagnostic use of PET in senile dementia.
— id: 9486, year: 1983, vol: 4, page: 568, stat: Journal Article,

Computed tomography and positron emission transaxial tomography evaluations of normal aging and Alzheimer's disease
de Leon MJ; Ferris SH; George AE; Reisberg B; Christman DR; Kricheff II; Wolf AP
1983 Sep;3(3):391-394, Journal of cerebral blood flow & metabolism
Young normal subjects, old normal subjects, and patients with senile dementia of the Alzheimer's type (SDAT) were studied with both computed tomography (CT) and positron emission transaxial tomography (PETT). Increases in ventricular size with both aging and disease were measured. Regional glucose metabolic rate was not affected by age, but was markedly reduced in SDAT patients. These data indicate that in normal aging, structural brain changes may be more salient than biochemical changes. Although both structural and biochemical changes occur in SDAT, the biochemical changes are more marked. The results suggest that PETT is potentially more useful than CT in the in vivo diagnosis of SDAT.
— id: 9485, year: 1983, vol: 3, page: 391, stat: Journal Article,

Regional correlation of PET and CT in senile dementia of the Alzheimer type
de Leon MJ; George AE; Ferris SH; Rosenbloom S; Christman DR; Gentes CI; Reisberg B; Kricheff II; Wolf AP
1983 May-Jun;4(3):553-556, AJNR. American journal of neuroradiology
Alzheimer disease is manifested by both widespread and regionally restricted brain changes, some of which have recently been identified in vivo with computed tomography (CT) and positron emission tomography (PET). This is a report of the regional correlation of CT and PET measurements in 19 carefully diagnosed subjects comprising 11 controls and eight patients with senile dementia of the Alzheimer type. Regional CT attenuation values did not discriminate between the two groups, but PET using 18F-2-deoxy-2-fluoro-D-glucose demonstrated significant regional reductions (range, 21%-28%) in glucose utilization in the Alzheimer group. PET measures were also more consistently related to cognitive decline. The correlation between CT structural measures and PET metabolic measures demonstrated consistent relations between widespread PET regions and CT changes in the thalamus, posterior limb of the internal capsule, and temporal lobes. However, CT changes in the frontal white matter, caudate nucleus, and anterior limb of the internal capsule were not related to any regional PET changes. These data support previous findings of temporal lobe involvement in Alzheimer disease and suggest the involvement of structures in the region of the third ventricle.
— id: 9487, year: 1983, vol: 4, page: 553, stat: Journal Article,

Positron emission tomography in dementia
Ferris SH; de Leon MJ; Wolf AP; George AE; Reisberg B; Christman DR; Yonekura Y; Fowler JS
1983 ;38:123-129, Advances in neurology
— id: 9489, year: 1983, vol: 38, page: 123, stat: Journal Article,

First results on the effects of MAO inhibition on cognitive functioning in elderly depressed patients
Georgotas A; Reisberg B; Ferris S
1983 Nov;2(3):249-254, Archives of gerontology & geriatrics
Elderly depressed patients who met the Research Diagnostic Criteria (RDC) for major depressive illness, were treated with phenelzine, a non-selective monoamine oxidase inhibitor, for a period of 2 to 7 wk, following 2 wk of placebo washout period. Possible pre- and post-treatment differences on the cognitive test battery were evaluated using the Wilcoxon test. Although recovery from depression was obtained in the majority of patients (Hamilton, Global and Self-rating Scales), none of the cognitive measures showed statistically significant changes over the course of the treatment period and the cognitive tests scores did not change as a result of treatment. It is of interest that tricyclic antidepressants (TCAs) are known to impair memory in geriatric patients, presumably due to their sedative and anticholinergic effects. The lack of an adverse cognitive effect for phenelzine therefore suggests a possible advantage of monoamine oxidase inhibitors over tricyclic antidepressants for the treatment of geriatric depression
— id: 18818, year: 1983, vol: 2, page: 249, stat: Journal Article,

Effects of naloxone in senile dementia: a double-blind trial
Reisberg B; Ferris SH; Anand R; Mir P; Geibel V; De Leon MJ; Roberts E
1983 Mar 24;308(12):721-722, New England journal of medicine
— id: 9488, year: 1983, vol: 308, page: 721, stat: Journal Article,

Novel pharmacologic approaches to the treatment of senile dementia of the Alzheimer's type (SDAT)
Reisberg B; London E; Ferris SH; Anand R; de Leon MJ
1983 Spring;19(2):220-225, Psychopharmacology bulletin
— id: 9491, year: 1983, vol: 19, page: 220, stat: Journal Article,

NALOXONE EFFECTS ON PRIMARY DEGENERATIVE DEMENTIA (PDD)
Reisberg, B; Ferris, SH; Anand, R; Mir, P; Deleon, MJ; Roberts, E
1983 ;19(1):45-47, Psychopharmacology bulletin
— id: 30675, year: 1983, vol: 19, page: 45, stat: Journal Article,

THE BRIEF COGNITIVE RATING-SCALE - LANGUAGE, MOTORIC, AND MOOD CONCOMITANTS IN PRIMARY DEGENERATIVE DEMENTIA
Reisberg, B; London, E; Ferris, SH; Borenstein, J; Scheier, L; Deleon, MJ
1983 ;19(4):702-708, Psychopharmacology bulletin
— id: 30604, year: 1983, vol: 19, page: 702, stat: Journal Article,

THE BRIEF COGNITIVE RATING-SCALE (BCRS) - FINDINGS IN PRIMARY DEGENERATIVE DEMENTIA (PDD)
Reisberg, B; Schneck, MK; Ferris, SH; Schwartz, GE; Deleon, MJ
1983 ;19(1):47-50, Psychopharmacology bulletin
— id: 30676, year: 1983, vol: 19, page: 47, stat: Journal Article,

CLINICAL ASSESSMENTS OF AGE-ASSOCIATED COGNITIVE DECLINE AND PRIMARY DEGENERATIVE DEMENTIA - PROGNOSTIC CONCOMITANTS
Reisberg, B; Shulman, E; Ferris, SH; Deleon, MJ; Geibel, V
1983 ;19(4):734-739, Psychopharmacology bulletin
— id: 30605, year: 1983, vol: 19, page: 734, stat: Journal Article,

A guide to Alzheimer's disease
Reisberg, Barry
New York : Free Press ; London : Collier Macmillan, 1983,
— id: 13, year: 1983, vol: , page: , stat: ,

Alzheimer's disease
Reisberg, Barry
New York : Free Press ; London : Collier Macmillan, c1983,
— id: 231, year: 1983, vol: , page: , stat: ,

POSITRON EMISSION TOMOGRAPHY (PET) STUDIES OF NORMAL AGING AND SENILE DEMENTIA OF THE ALZHEIMERS TYPE (SDAT)
Deleon, MJ; Ferris, SH; George, AE; Christman, DR; Fowler, J; Gentes, C; Gee, B; Reisberg, B; Kricheff, II; Wolf, A
1982 ;22(4):53-54, Gerontologist
— id: 30369, year: 1982, vol: 22, page: 53, stat: Journal Article,

POSITRON EMISSION TOMOGRAPHY AND COMPUTED-TOMOGRAPHY CORRELATES IN SENILE DEMENTIA
Deleon, MJ; Ferris, SH; George, AE; Kricheff, II; Christman, D; Reisberg, B; Fowler, J; Rosenbloom, S; Gentes, C; Wolf, AP
1982 ;3(1):96-96, AJNR. American journal of neuroradiology
— id: 30470, year: 1982, vol: 3, page: 96, stat: Journal Article,

18F-2-deoxy-2-fluoro-D-glucose as a tracer in the positron emission tomographic study of senile dementia
Farkas T; Ferris SH; Wolf AP; De Leon MJ; Christman DR; Reisberg B; Alavi A; Fowler JS; George AE; Reivich M
1982 Mar;139(3):352-353, American journal of psychiatry
— id: 9494, year: 1982, vol: 139, page: 352, stat: Journal Article,

PIRACETAM IN THE TREATMENT OF COGNITIVE IMPAIRMENT IN THE ELDERLY
REISBERG B; FERRIS S H; SCHNECK M K; CORWIN J; MIR P; FRIEDMAN E; SHERMAN K A; MCCARTHY M; BARTUS R T
1982 ;2(5):475-480, Drug development research
Piracetam (Nootropil, 2-oxopyrrolidone acetamide) has been extensively investigated for the treatment of cognitive impairment. Initial studies on normal subjects and patients with mild or moderate cognitive decline have been somewhat encouraging. A further evaluation of the effects of piracetam was conducted in the treatment of elderly outpatients 60-85 yr of age with mild to moderate memory impairment consistent with a diagnosis of Primary Degenerative Dementia (PDD). The effects of piracetam in 20 patients were examined. All patients received 7.2 g of piracetam and placebo for 4 wk in accordance with a double-blind, randomized treatment order, crossover design with 1-wk washout periods prior to each crossover period. The total study period for each patient was 10 wk (1-4-1-4). An analysis of 43 psychometric measures revealed significant improvement (P < 0.05) in only 3 measures, all favoring the treatment conjunction with cholinergic precursors in patients with cognitive decline. In a 2nd study, a 1-wk open trial of 1.6 g of piracetam t.i.d. [3 times a day] in conjunction with 3 g of choline chloride t.i.d. was conducted in 15 patients. Four patients were rated as clinically improved. These responders were all subjects with moderate cognitive impairment. The responders showed much higher RBC [red blood cell] choline levels than the nonresponders, both at baseline and during treatment. The effects of piracetam treatment alone in elderly outpatients with mild to moderate cognitive decline are subtle and not of proven clinical significance. Studies of longer duration and of piracetam in combination with other agents may eventually show genuine clinical utility
— id: 98835, year: 1982, vol: 2, page: 475, stat: Journal Article,

Diagnosis and assessment of the older patient
Reisberg B; Ferris SH
1982 Feb;33(2):104-110, Hospital & community psychiatry
Despite the enormous medical and psychiatric importance of mental illness among the elderly, clinicians generally are not trained in the phenomenology and presentation of the major mental disorders that occur primarily in this age group. The authors describe the presenting symptoms and course of four conditions--senescent forgetfulness, primary degenerative dementia (considered as the confusional phase and dementia phase), geriatric depression, and multi-infarct dementia--with emphasis on differential diagnosis. The clinical examination of the patient is the most important feature of any diagnostic and assessment program; because of the wide prevalence and in many ways unique aspects of mental illness among the elderly, all but the smallest psychiatric programs should have at least one clinician who specializes in assessment of geriatric problems
— id: 18819, year: 1982, vol: 33, page: 104, stat: Journal Article,

The Global Deterioration Scale for assessment of primary degenerative dementia
Reisberg B; Ferris SH; de Leon MJ; Crook T
1982 Sep;139(9):1136-1139, American journal of psychiatry
Cognitive decline associated with old age and consistent with the diagnosis of primary degenerative dementia is a unique clinical syndrome with characteristic phenomena and progression. The authors describe a Global Deterioration Scale for the assessment of primary degenerative dementia and delineation of its stages. The authors have used the Global Deterioration Scale successfully for more than 5 years and have validated it against behavioral, neuroanatomic, and neurophysiologic measures in patients with primary degenerative dementia.
— id: 9493, year: 1982, vol: 139, page: 1136, stat: Journal Article,

Relationship between cognition and mood in geriatric depression
Reisberg B; Ferris SH; Georgotas A; de Leon MJ; Schneck MJ
1982 Oct;18(4):191-193, Psychopharmacology bulletin
— id: 9492, year: 1982, vol: 18, page: 191, stat: Journal Article,

An overview of current concepts of Alzheimer's disease
Schneck MK; Reisberg B; Ferris SH
1982 Feb;139(2):165-173, American journal of psychiatry
— id: 18820, year: 1982, vol: 139, page: 165, stat: Journal Article,

POSITRON EMISSION TOMOGRAPHY AND COMPUTED-TOMOGRAPHY EVALUATIONS OF REGIONAL BRAIN METABOLISM IN SENILE DEMENTIA
Deleon, MJ; Ferris, SH; George, AE; Rosenbloom, S; Reisberg, B; Christman, DR; Fowler, J; Gentes, C; Emmerich, M; Wolf, A
1981 ;4(4):146-146, Age
— id: 30505, year: 1981, vol: 4, page: 146, stat: Journal Article,

Clinical response to choline plus piracetam in senile dementia: relation to red-cell choline level
Friedman E; Sherman KA; Ferris SH; Reisberg B; Bartus RT; Schneck MK
1981 Jun 11;304(24):1490-1491, New England journal of medicine
— id: 18822, year: 1981, vol: 304, page: 1490, stat: Journal Article,

Clinical profiles of tardive dyskinesia
Itil TM; Reisberg B; Huque M; Mehta D
1981 May-Jun;22(3):282-290, Comprehensive psychiatry
— id: 34312, year: 1981, vol: 22, page: 282, stat: Journal Article,

Extrapyramidal symptoms in patients with primary degenerative dementia
Pomara N; Reisberg B; Albers S; Ferris S; Gershon S
1981 Nov;1(6):398-400, Journal of clinical psychopharmacology
— id: 18821, year: 1981, vol: 1, page: 398, stat: Journal Article,

An overview of pharmacologic treatment of cognitive decline in the aged
Reisberg B; Ferris SH; Gershon S
1981 May;138(5):593-600, American journal of psychiatry
The most widely known substances that have been investigated for treating cognitive deterioration in the aged are cerebral vasodilators, Gerovital H3, psychostimulants, 'nootropics,' neuropeptides, and neurotransmitters. The rationale for the choice of specific agents has shifted as our conceptions regarding the origins of cognitive decline have changed; we now know that most cognitive deterioration occurs independently of arteriosclerotic vascular changes. Substances currently being investigated because of their effects on brain electrophysiology, on neurohumoral processes, or on central neurotransmitters show promise
— id: 18823, year: 1981, vol: 138, page: 593, stat: Journal Article,

The relationship between psychiatric assessments and cognitive test measures in mild to moderately cognitively impaired elderly [proceedings]
Reisberg B; Ferris SH; Schneck MK; de Leon MJ; Crook TH; Gershon S
1981 Jan;17(1):99-101, Psychopharmacology bulletin
— id: 9497, year: 1981, vol: 17, page: 99, stat: Journal Article,

Brain failure : an introduction to current concepts of senility
Reisberg, Barry
New York : Free Press, 1981,
— id: 126, year: 1981, vol: , page: , stat: ,

Computed tomography evaluations of brain-behavior relationships in senile dementia of the Alzheimer's type
De Leon MJ; Ferris SH; George AE; Reisberg B; Kricheff II; Gershon S
1980 Summer;1(1):69-79, Neurobiology of aging
Neuropathological investigations have demonstrated brain-behavior relationships in senile dementia of the Alzheimer's type (SDAT), but CT studies have not produced consistent findings. We hypothesized that these discouraging results were in part due to limitations in the methods of CT scan evaluations, and to non-homogeneity of patient populations. The present study examined 43 out-patients with the presumptive diagnosis of SDAT using 37 cognitive test measures and 3 independent CT evaluation strategies. The CT methods included a new rank ordering procedure and two previously used techniques, physical measurement and 4-point rating. Highly significant (p less than or equal to 0.01) brain-behavior correlations were attained using the ranking and rating procedures for evaluation of ventricular and cortical pathology. It was found that rank ordering has high interrater reliability and is superior to the other methods for the evaluation of the ventricular system. The physical measurement of the third ventricle is the single most powerful linear correlate of cognitive impairment. Measurement of cortical sulci are of no correlational significance. Multiple regression analyses indicated that global assessments are the best cognitive predictors of both ventricular and cortical pathology. Thus the present study has demonstrated brain-behavior relationships in vivo in SDAT.
— id: 9498, year: 1980, vol: 1, page: 69, stat: Journal Article,

REGIONAL BRAIN METABOLISM IN AGING AND SENILE DEMENTIA DETERMINED BY POSITRON EMISSION TOMOGRAPHY
Ferris, SH; Farkas, I; Alavi, A; Deleon, M; Rampal, S; Reisberg, B; Christman, D; Fowler, J; Reivich, M; Wolf, A
1980 ;3(4):113-113, Age
— id: 27937, year: 1980, vol: 3, page: 113, stat: Journal Article,

ELEVATION OF SISTER CHROMATID EXCHANGES IN FEMALE ALZHEIMERS- DISEASE PATIENTS
Fischman, HK; Albu, P; Reisberg, B; Ferris, S; Rainer, JD
1980 ;32(6):A69-A69, American journal of human genetics
— id: 27939, year: 1980, vol: 32, page: A69, stat: Journal Article,

CLINICAL EFFICACY AND SAFETY OF MAOIS IN DEPRESSED ELDERLY
Georgotas, A; Ferris, S; Friedman, E; Mann, J; Reisberg, B; Gershon, S
1980 ;3(4):113-113, Age
— id: 28081, year: 1980, vol: 3, page: 113, stat: Journal Article,

Psychostimulants and neuropeptides in geropsychiatry [proceedings]
Gershon S; Crook T; Ferris S; Reisberg B
1980 Oct;16(4):31-34, Psychopharmacology bulletin
— id: 18824, year: 1980, vol: 16, page: 31, stat: Journal Article,

Pharmacotherapy of senile dementia
Reisberg B; Ferris SH; Gershon S
1980 ;69(1):233-264, Proceedings of the annual meeting of the American Psychopthological Association
— id: 18825, year: 1980, vol: 69, page: 233, stat: Journal Article,

EFFECTS OF PIRACETAM IN THE COGNITIVELY IMPAIRED AGED
Reisberg, B; Ferris, SH; Corwin, J; Mccarthy, M; Schneck, M
1980 ;3(4):113-113, Age
— id: 28082, year: 1980, vol: 3, page: 113, stat: Journal Article,

Correlations between computerised tomographic changes and behavioural deficits in senile dementia
de Leon MJ; Ferris SH; Blau I; George AE; Reisberg B; Kricheff II; Gershon S
1979 Oct 20;2(8147):859-860, Lancet
— id: 9499, year: 1979, vol: 2, page: 859, stat: Journal Article,

CT CORRELATES OF COGNITIVE DEFICITS IN SENILE DEMENTIA
Deleon, MJ; Ferris, SH; George, AE; Blau, I; Reisberg, B
1979 ;2(4):130-130, Age
— id: 28041, year: 1979, vol: 2, page: 130, stat: Journal Article,

Long-term choline treatment of memory-impaired elderly patients
Ferris SH; Sathananthan G; Reisberg B; Gershon S
1979 Sep 7;205(4410):1039-1040, Science
— id: 18826, year: 1979, vol: 205, page: 1039, stat: Journal Article,

Side effects associated with lithium therapy
Reisberg B; Gershon S
1979 Jul 20;36(8 Spec No):879-887, Archives of general psychiatry
— id: 34313, year: 1979, vol: 36, page: 879, stat: Journal Article,

Pharmacologic treatment of aggressive syndromes
Itil TM; Reisberg B
1978 ;18(1):137-142, Current psychiatric therapies
— id: 34316, year: 1978, vol: 18, page: 137, stat: Journal Article,

Use of psychotropics in the world
Itil TM; Reisberg B; Simeon S
1978 ;13(1):39-49, International pharmacopsychiatry
A questionnaire regarding medication preferences for major categories of psychiatric disorders was sent to 1,059 psychiatric drug investigators in 53 countries. 264 questionnaires were returned, of which 165 were appropriate for this survey. A total of 87 different psychotropic drugs were selected. Chlorpromazine was the medication most frequently cited in the treatment of schizophrenia. Amitriptyline and imipramine together accounted for the vast majority of medication chosen for all varieties of depression. In the treatment of mania, chlorpromazine was chosen by almost one-third of our sample, lithium by only one-fifth. Chlordiazepoxide and diazepam were equally preferred in the treatment of alcoholism. Most psychiatrists preferred not to use any psychotropic medications consistently in treating patients with organic brain syndromes. The implications of this study are discussed and compared uith similar studies in more limited geographical regions and in children
— id: 34315, year: 1978, vol: 13, page: 39, stat: Journal Article,

Catatonia associated with disulfiram therapy
Reisberg B
1978 Aug;166(8):607-609, Journal of nervous & mental disease
This is the first report of a catatonic syndrome occurring in a patient receiving disulfiram treatment. A causal relationship is strongly suggested by the mode of onset, the absence of a previous history of catatonia, and the rapid resolution of the syndrome within 72 hours of discontinuance of the disulfiram therapy. Neurophysiological mechanisms which aid in elucidating the role of disulfiram in the etiology of catatonia are discussed. It is important that physicians be alerted to this serious, potentially lethal, complication, as it is readily reversible if the disulfiram is discontinued and appropriate supportive measures are taken. Also, it appears that these patients may be more susceptible to complications with future disulfiram usage and should be strongly counseled to seek alternative therapies for their alcohol problems in the future
— id: 34314, year: 1978, vol: 166, page: 607, stat: Journal Article,

Transcultural aspects of psychopharmacology
Itil TM; Reisberg B
1977 ;17(1):325-332, Current psychiatric therapies
— id: 34317, year: 1977, vol: 17, page: 325, stat: Journal Article,