Nunzio Pomara, M.D.

Cerebrospinal fluid cortisol concentrations in healthy elderly are affected by both APOE and TOMM40 variants
Bruno D; Nierenberg JJ; Ritchie JC; Lutz MW; Pomara N
2011 Jul 30;:366-371 #, Psychoneuroendocrinology
Abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis have been reported in subjects with Alzheimer's disease (AD) and may include increased cerebrospinal fluid (CSF) cortisol concentrations. Moreover, presence of the APOE varepsilon4 allele, which is an established risk factor for the development of AD, has been shown to associate with higher CSF cortisol levels, especially in AD sufferers. In this study, we examined whether TOMM40 variants, which have been reported to influence age of onset of AD, also had an effect on CSF cortisol levels, in healthy, cognitively intact individuals with or without APOE varepsilon4. In our results, the increase in CSF cortisol associated with the presence of the APOE varepsilon4 allele was only detected when a short TOMM40 poly-T variant, shown to associate with later age of onset of AD in varepsilon4 carriers, was not present. These results are consistent with previous reports (e.g., Roses et al., 2009) suggesting that TOMM40 poly-T variants influence the effects of APOE alleles
— id: 136654, year: 2011, vol: , page: 366, stat: Journal Article,

Levels of cerebrospinal fluid neurofilament light protein in healthy elderly vary as a function of TOMM40 variants
Bruno D; Pomara N; Nierenberg JJ; Ritchie JC; Lutz MW; Zetterberg H; Blennow K
2011 Oct 1;:?-? #, Experimental gerontology
Neurofilament light (NFL) proteins in cerebrospinal fluid (CSF) are a marker of neuronal damage, especially subcortical axonal injury and white matter disease. Subjects with Alzheimer's disease (AD) have shown elevated levels of CSF NFL as compared to controls. However, the presence of the APOE epsilon4 allele, an established risk factor for AD, was not found to associate with higher CSF NFL concentrations. We examined whether TOMM40 variants, which have been reported to influence age of onset of AD and are in linkage disequilibrium with APOE, have an effect on CSF NFL levels, in 47 healthy, cognitively intact individuals with or without APOE epsilon4. Our results show that the presence of APOE epsilon4 alone does not affect CSF NFL levels significantly; however APOE and TOMM40 appear to interact. Subjects with APOE epsilon4 have higher CSF NFL levels than non-epsilon4 carriers, only when they do not carry a short poly-T variant of TOMM40, which is associated with later age of onset of AD, and may act as protective against the dose effect of epsilon4
— id: 145999, year: 2011, vol: , page: ?, stat: Journal Article,

Decreased learning and recall of primacy words as predictors of decline in healthy individuals
Pomara N.; Bruno D.; Reiss P.; Petkova E.; Sidtis J.
2011 ;8:?-?, Neuro-degenerative diseases
Introduction: An important goal of ongoing Alzheimer's disease (AD) research is to identify markers that allow one to predict risk for the development of this type of dementia in cognitively intact elderly. Known cognitive changes associated with AD, possibly reflecting hippocampal pathology, include a worse recall of primacy items and better immediate recall of items learned at the end of a list compared to the middle (recency effect). Aims: The aim of our study was to examine whether learning and recall of primacy and recency words predicted future decline in intact elderly subjects. Methods: Individuals with MMSE of 28 or over at baseline were included in the study. Of these, 211 had at least two successive cognitive evaluations; mean age at baseline was 69.5 (SD=8.0). We regressed MMSE decline on baseline Auditory-Verbal Learning Test (AVLT) memory measures, focusing especially on learning and recall of primacy and recency words, and controlling for baseline age, time since baseline and other variables. Results: Worse learning/delayed recall of primacy words on AVLT trials consistently predicted greater subsequent cognitive decline. Additionally, this effect was stronger among older subjects than among younger ones. APOE e4, a well established genetic risk factor for late-onset AD, was not a significant predictor of MMSE decline in this sample. Conclusions: Decreased learning and poorer recall of primacy words in the AVLT is a predictor of decline in healthy elderly individuals, and future studies should examine if decreased learning and recall can predict conversion to AD
— id: 136535, year: 2011, vol: 8, page: ?, stat: Journal Article,

TOMM40 poly-T Variants and Cerebrospinal Fluid Amyloid Beta Levels in the Elderly
Pomara N; Bruno D; Nierenberg JJ; Sidtis JJ; Martiniuk FT; Mehta PD; Zetterberg H; Blennow K
2011 Jun;36(6):1124-1128, Neurochemical research
A variable poly-T polymorphism in the TOMM40 gene, which is in linkage disequilibrium with APOE, was recently implicated with increased risk and earlier onset age for late-onset Alzheimer's disease in APOE epsilon3 carriers. To elucidate potential neurobiological mechanisms underlying this association, we compared the effect of TOMM40 poly-T variants to the effect of APOE, an established LOAD-risk modulator, on cerebrospinal fluid (CSF) amyloid beta (Abeta) and tau levels, in cognitively intact elderly subjects. APOE epsilon4 carriers showed significant reductions in Abeta 1-42 levels compared to non-epsilon4 carriers, but no differences were detected across TOMM40 variants. Neither Abeta 1-40 nor tau levels were affected by APOE or TOMM40
— id: 131223, year: 2011, vol: 36, page: 1124, stat: Journal Article,

Lower plasma {beta}-amyloid levels are associated with moderately greater rate of cognitive decline among older people without dementia
Pomara, Nunzio; Bruno, Davide
2011 May;14(2):41-41, Evidence-based mental health
— id: 131222, year: 2011, vol: 14, page: 41, stat: Journal Article,

Potential effects of the APOE {varepsilon}2 allele and of family history of Alzheimer\'s disease on brain amyloid-beta in normal elderly
Pomara, Nunzio; Bruno, Davide
2011 Nov 8;108(45):E1007-E1007, Proceedings of the National Academy of Sciences of the United States of America
— id: 145998, year: 2011, vol: 108, page: E1007, stat: Journal Article,

Plasma beta-amyloid level, cognitive reserve, and cognitive decline
Pomara, Nunzio; Bruno, Davide; Sidtis, John J
2011 Apr 27;305(16):1655-1655, JAMA
— id: 131667, year: 2011, vol: 305, page: 1655, stat: Journal Article,

Translocase of Outer Mitochondrial Membrane 40 Homolog (TOMM40) Poly-T Length Modulates Lorazepam-Related Cognitive Toxicity in Healthy APOE ϵ4-Negative Elderly
Pomara, Nunzio; Bruno, Davide; Sidtis, John J; Lutz, Michael W; Greenblatt, David J; Saunders, Ann M; Roses, Allen D
2011 Aug;31(4):544-546, Journal of clinical psychopharmacology
— id: 134922, year: 2011, vol: 31, page: 544, stat: Journal Article,

Alzheimer's disease
Pomara, Nunzio; Sidtis, John J
2010 May 13;362(19):1844-1844, New England journal of medicine
— id: 109816, year: 2010, vol: 362, page: 1844, stat: Journal Article,

Brain neurotoxic amyloid-beta peptides: their potential role in the pathophysiology of depression and as molecular therapeutic targets
Pomara, Nunzio; Sidtis, John J
2010 Oct;161(4):768-770, British journal of pharmacology
The monoamine hypothesis ascribes an important role to the under activity of brain monoamines such as 5-HT, noradrenaline and dopamine to the pathophysiology of depression. This view emerged more than 50 years ago and has guided development of most medications currently used for the treatment of this disorder. However, large numbers of depressed individuals treated with currently available antidepressant agents, or even with various combinations, do not respond. Residual symptoms, relapses and recurrences are common while receiving adequate doses of these medications. In a recent issue of the BJP, Colaianna et al.describe results suggesting that a new neurobiological mechanism with treatment implications should be considered for the development of depression in humans, namely, elevations in potentially neurotoxic brain amyloid-ss peptides
— id: 114798, year: 2010, vol: 161, page: 768, stat: Journal Article,

Retrograde facilitation of verbal memory by trihexyphenidyl in healthy elderly with and without the APOE epsilon4 allele
Pomara, Nunzio; Yi, Linlin; Belzer, Ken; Facelle, Thomas M; Willoughby, Lisa M; Sidtis, John J
2010 Jul;20(7):467-472, European neuropsychopharmacology
Retrograde facilitation (RF) of information learned prior to acute oral administration of trihexyphenidyl, a preferential muscarinic M1 receptor antagonist which impairs new learning, was studied in 24 healthy elderly subjects. The relationship between the RF induced by this anticholinergic drug and the APOE epsilon4 allele was also examined. Acute adverse performance effects of trihexyphenidyl (1- and 2mg) were determined using the Buschke Selective Reminding Test administered pre-drug and at 1, 2.5, and 5h post-drug. Recall of pre-drug words at the end of the fifth hour neuropsychological assessment (end-of-session recall) was of primary interest. Words studied before drug administration were better recalled following 2mg trihexyphenidyl compared to placebo, and this RF effect was not affected by the APOE epsilon4 allele. Better recall of pre-drug words following 2-mg trihexyphenidyl was associated with a greater amnestic effect of this dose. Our findings demonstrated that RF induced by trihexyphenidyl was related to anterograde amnestic effects of the drug and resulted in part from drug-induced reduction of retroactive interference
— id: 138186, year: 2010, vol: 20, page: 467, stat: Journal Article,

Serial Position Effects In Normals at Risk for AD
Pomara, N; Schmeltz, AL; Sidtis, JJ
2009 APR 15 ;65(8):47S-47S, Biological psychiatry
— id: 97975, year: 2009, vol: 65, page: 47S, stat: Journal Article,

Apolipoprotein E epsilon4: an understudied potential pharmacodynamic risk factor of drug-induced cognitive toxicity in the elderly
Pomara, Nunzio
2009 Jun;29(3):312-313, Journal of clinical psychopharmacology
— id: 146000, year: 2009, vol: 29, page: 312, stat: Journal Article,

Lithium treatment in Alzheimer's disease does not promote cognitive enhancement, but may exert long-term neuroprotective effects
Pomara, Nunzio
2009 Jul;205(1):169-170, Psychopharmacology
— id: 146001, year: 2009, vol: 205, page: 169, stat: Journal Article,

Reduction in muscarinic m1-mediated hypercholinergic state and beneficial cognitive effects of muscarinic agonists in schizophrenia
Pomara, Nunzio
2009 Jan;166(1):111-111, American journal of psychiatry
— id: 91356, year: 2009, vol: 166, page: 111, stat: Journal Article,

Suicidal behavior: The need for its documentation in multiaxial DSM-V diagnoses
Pomara, Nunzio
2009 Mar;166(3):371-371, American journal of psychiatry
— id: 97037, year: 2009, vol: 166, page: 371, stat: Journal Article,

Apolipoprotein E epsilon4 and anticholinergic cognitive toxicity
Pomara, Nunzio; Sidtis, John
2009 Nov;57(11):2151-2151, Journal of the American Geriatrics Society
— id: 136655, year: 2009, vol: 57, page: 2151, stat: Journal Article,

Does cortical thinning in persons at increased risk for major depression also increase their risk for Alzheimer's disease?
Pomara, Nunzio; Sidtis, John
2009 Jul 21;106(29):E82-E82, Proceedings of the National Academy of Sciences of the United States of America
— id: 100578, year: 2009, vol: 106, page: E82, stat: Journal Article,

Increased Mental Slowing Associated With the APOE {varepsilon}4 Allele After Trihexyphenidyl Oral Anticholinergic Challenge in Healthy Elderly
Pomara, Nunzio; Belzer, Ken; Hernando, Raymundo; De La Pena, Corazon; Sidtis, John J
2008 Feb;16(2):116-124, American journal of geriatric psychiatry
Objectives: The objectives of this study were to examine the relationship between APOE epsilon4 and subjective effects of trihexyphenidyl on measures reflecting sedation and confusion and to investigate the relationship between trihexyphenidyl-induced subjective effects and objective memory performance. Methods: This study comprised 24 cognitively intact, health elderly adults (12 APOE epsilon4 carriers) at an outpatient geriatric psychiatry research clinic. This was a randomized, double blind, placebo-controlled, three-way, crossover experimental design. All participants received 1.0 mg or 2.0 mg trihexyphenidyl or placebo administered in counterbalanced sequences over a period of three consecutive weeks. Bond and Lader's visual analog scales and alternate versions of the Buschke Selective Reminding Test were administered in a repeated measures design at baseline, 1, 2.5, and 5 hours postdrug administration. Results: A 2.0-mg oral dose of trihexyphenidyl resulted in increased subjective ratings of mental slowness in carriers of the APOE epsilon4 allele only. Drug effects as determined by difference scores between 2.0 mg trihexyphenidyl and placebo on ratings of mental slowness significantly correlated with total and delayed recall on the Buschke Selective Reminding Test in carriers of the APOE epsilon4 allele only. However, no significant effects were found with other visual analog scales reflecting subjective sedation and clear-headedness. Conclusion: The epsilon4 allele in healthy elderly was associated with increased subjective mental slowing after trihexyphenidyl anticholinergic challenge
— id: 75708, year: 2008, vol: 16, page: 116, stat: Journal Article,

The apolipoprotein E varepsilon4 allele and memory performance in HIV-1 seropositive subjects: differences at baseline but not after acute oral lorazepam challenge
Pomara, Nunzio; Belzer, Kenneth D; Silva, Raul; Cooper, Thomas B; Sidtis, John J
2008 Nov;201(1):125-135, Psychopharmacology
RATIONALE: The APOE varepsilon4 allele, an established genetic risk factor for late-onset Alzheimer's disease, has been linked to an increased risk for dementia especially in older individuals with HIV-1 infection. This allele has also been associated with increased memory impairment following oral lorazepam challenge in healthy elderly. Lorazepam and other benzodiazepines are widely prescribed in individuals with HIV-1 infection who are at increased risk for cognitive impairment. OBJECTIVE: The aim of this study was to examine if the varepsilon4 allele influences lorazepam-induced memory deficits in this population. MATERIALS AND METHODS: Forty-one non-demented, HIV-1 seropositive adults (15 varepsilon4 carriers, mean age = 43.47 +/- 8.25; 26 varepsilon4 non-carriers, mean age = 46.77 +/- 8.56) participated in a double-blind, placebo-controlled crossover design, receiving single acute oral doses of lorazepam 0.5, 1.0 mg, or placebo over three sessions, each 1 week apart. Standardized neuropsychological assessments, including measures of immediate and delayed verbal recall, were conducted at baseline and at 1, 2.5, and 5 h post-drug administration in each condition. RESULTS: Acute lorazepam administration produced dose- and time-dependent impairments in measures of verbal recall. However, the e4 allele did not modulate these adverse effects. An APOE varepsilon4 group by time interaction was also found such that the APOE-varepsilon4-positive subjects had significantly better immediate and delayed verbal recall than the negative subjects at baseline assessment, but the groups did not significantly differ at any subsequent time point. CONCLUSION: Future studies should clarify the role of varepsilon4 in the modulation of drug-induced cognitive toxicity and baseline performance and their relationship to progressive decline, especially in older individuals with HIV-1 infection, a group at increased risk for dementia
— id: 80341, year: 2008, vol: 201, page: 125, stat: Journal Article,

Deleterious CNS effects of the APOE epsilon4 allele in individuals with HIV-1 infection may be age-dependent
Pomara, Nunzio; Belzer, Kenneth; Sidtis, John J
2008 Oct 14;105(41):E65-E65, Proceedings of the National Academy of Sciences of the United States of America
— id: 91357, year: 2008, vol: 105, page: E65, stat: Journal Article,

Memantine treatment of cognitive symptoms in mild to moderate Alzheimer disease: secondary analyses from a placebo-controlled randomized trial
Pomara, Nunzio; Ott, Brian R; Peskind, Elaine; Resnick, E Malca
2007 Jan-Mar;21(1):60-64, Alzheimer disease & associated disorders
Memantine, an N-methyl-D-aspartate receptor antagonist, is approved in the United States and Europe for the treatment of moderate to severe Alzheimer disease (AD) and has also been investigated in patients with mild to moderate AD. To characterize the specific cognitive benefits of memantine in patients with mild to moderate AD, a post hoc analysis was conducted of a 24-week randomized, double-blind, placebo-controlled, clinical trial comparing memantine (10 mg twice daily) to placebo. Cognition was assessed using the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) total score, individual items, and aggregated subscales, using a mixed model repeated measures analysis. As assessed by the ADAS-cog total score, participants in the placebo group demonstrated significantly more cognitive decline from baseline than participants treated with memantine at all visits beginning at week 8. Subjects treated with placebo also declined significantly more than individuals in the memantine group on 5 of 11 ADAS-cog individual items: orientation, language, comprehension, word finding, and recall of test instructions. Out of 3 ADAS-cog aggregated item subscales (language, memory, and praxis), outcomes in 2 (language and memory) favored memantine. Consistent with findings from trials conducted in moderate to severe AD patients, this post hoc analysis of a randomized clinical trial suggests that memantine benefits core aspects of language and some aspects of memory in patients with mild to moderate AD
— id: 72411, year: 2007, vol: 21, page: 60, stat: Journal Article,

Possible therapeutic implication of Abeta disturbances in depression
Pomara, Nunzio; Sidtis, John
2007 Sep;22(9):931-932, International journal of geriatric psychiatry
— id: 73081, year: 2007, vol: 22, page: 931, stat: Journal Article,

Memantine Treatment in Mild to Moderate Alzheimer Disease: A 24-Week Randomized, Controlled Trial
Peskind ER; Potkin SG; Pomara N; Ott BR; Graham SM; Olin JT; McDonald S
2006 Jul 21;:?-?, American journal of geriatric psychiatry
Objective: The objective of this study was to compare the efficacy and safety of the moderate-affinity, uncompetitive N-methyl-d-aspartate receptor antagonist, memantine, versus placebo in patients with mild to moderate Alzheimer disease (AD). Method: This was a randomized, double-blind, placebo-controlled clinical trial conducted at 42 U.S. sites. Participants were 403 outpatients with mild to moderate AD and Mini-Mental State Examination scores of 10-22 randomized to memantine (20 mg/day; N = 201) or placebo (N = 202) for 24 weeks. Primary outcomes were change from baseline at 24 weeks on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog), a measure of cognition, and on the Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus), a global measure. Secondary outcomes included change on the Neuropsychiatric Inventory (NPI) and the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL23), measures of behavior and function, respectively. Results: Most (82.4%) participants completed the trial. Memantine resulted in significantly better outcomes than placebo on measures of cognition, global status, and behavior when based on the protocol-specified primary last observation carried forward imputation as well as a mixed-models repeated-measures approach applied to the continuous outcomes. Treatment discontinuations because of adverse events for memantine versus placebo were 19 (9.5%) and 10 (5.0%), respectively. Conclusions: These results support the safety and efficacy of memantine for the treatment of mild to moderate AD
— id: 97038, year: 2006, vol: , page: ?, stat: Journal Article,

Memantine treatment in mild to moderate Alzheimer disease: a 24-week randomized, controlled trial
Peskind, Elaine R; Potkin, Steven G; Pomara, Nunzio; Ott, Brian R; Graham, Stephen M; Olin, Jason T; McDonald, Scott
2006 Aug;14(8):704-715, American journal of geriatric psychiatry
OBJECTIVE: The objective of this study was to compare the efficacy and safety of the moderate-affinity, uncompetitive N-methyl-d-aspartate receptor antagonist, memantine, versus placebo in patients with mild to moderate Alzheimer disease (AD). METHOD: This was a randomized, double-blind, placebo-controlled clinical trial conducted at 42 U.S. sites. Participants were 403 outpatients with mild to moderate AD and Mini-Mental State Examination scores of 10-22 randomized to memantine (20 mg/day; N=201) or placebo (N=202) for 24 weeks. Primary outcomes were change from baseline at 24 weeks on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog), a measure of cognition, and on the Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus), a global measure. Secondary outcomes included change on the Neuropsychiatric Inventory (NPI) and the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL(23)), measures of behavior and function, respectively. RESULTS: Most (82.4%) participants completed the trial. Memantine resulted in significantly better outcomes than placebo on measures of cognition, global status, and behavior when based on the protocol-specified primary last observation carried forward imputation as well as a mixed-models repeated-measures approach applied to the continuous outcomes. Treatment discontinuations because of adverse events for memantine versus placebo were 19 (9.5%) and 10 (5.0%), respectively. CONCLUSIONS: These results support the safety and efficacy of memantine for the treatment of mild to moderate AD
— id: 69566, year: 2006, vol: 14, page: 704, stat: Journal Article,

Are plasma A beta 42 levels elevated in late-life major depression?
Pomara, N; Doraismamy, PM; Willoughby, LM; Roth, AE; Mulsant, BH; Sidtis, JJ; Mehta, PD; Reynolds, CF; Pollock, BG
2006 APR 15 ;59(8):177S-177S, Biological psychiatry
— id: 63863, year: 2006, vol: 59, page: 177S, stat: Journal Article,

DTI measures in the insular region: Relationship to autonomic indices, laterality and APOE E4 in healthy elderly
Pomara, N; Lim, KO; Sidtis, JJ; Nierenberg, J
2006 DEC ;31(2):S211-S211, Neuropsychopharmacology
— id: 70915, year: 2006, vol: 31, page: S211, stat: Journal Article,

Enhanced retrograde facilitation of primacy words in healthy elderly with the APOE-e4 allele after acute lorazepam administration
Pomara, N; Roth, AE; Willoughby, L; Wesnes, K; Greenblatt, DJ; Sidtis, JJ
2006 APR 15 ;59(8):250S-250S, Biological psychiatry
— id: 63864, year: 2006, vol: 59, page: 250S, stat: Journal Article,

Elevation in plasma Abeta42 in geriatric depression: a pilot study
Pomara, Nunzio; Doraiswamy, P Murali; Willoughby, Lisa M; Roth, Amy E; Mulsant, Benoit H; Sidtis, John J; Mehta, Pankaj D; Reynolds, Charles F 3rd; Pollock, Bruce G
2006 Mar;31(3):341-349, Neurochemical research
Elevated plasma amyloid beta 1-42 (Abeta42) level has been linked to increased risk for incident AD in cognitively-intact elderly. However, plasma Abeta levels in individuals with late-life depression (LLMD), especially those with a late age of onset of first depressive episode, who are at a particularly increased risk for Alzheimer's disease, have not been studied. We compared plasma Abeta in 47 elderly with LLMD with 35 controls and examined its relationships to age of onset of first depressive episode, antidepressant treatment (paroxetine or nortriptyline), and indices of platelet activation (platelet factor 4 and beta-thromboglobulin) and brain abnormalities. Results indicated that plasma Abeta42 levels and the Abeta42/40 ratio were elevated in the LLMD group relative to controls in the overall group analyses and in the age- and gender-matched groups. MRI data indicated that higher Abeta42/40 ratio was associated with greater severity of total white matter hyperintensity burden in LLMD. Plasma Abeta levels in LLMD were not influenced by age of onset of first depressive episode or antidepressant treatment and were not related to indices of platelet activation. Our preliminary results suggest that increased plasma Abeta42 and Abeta42/40 ratio are present in geriatric depression, and future studies should be done to confirm these findings and to determine their relationship to cognitive decline and brain abnormalities associated with LLMD
— id: 69568, year: 2006, vol: 31, page: 341, stat: Journal Article,

Dose-dependent retrograde facilitation of verbal memory in healthy elderly after acute oral lorazepam administration
Pomara, Nunzio; Facelle, Thomas M; Roth, Amy E; Willoughby, Lisa M; Greenblatt, David J; Sidtis, John J
2006 May;185(4):487-494, Psychopharmacology
RATIONALE: Retrograde facilitation (RF) refers to a paradoxical phenomenon in which recall of information presented before acute administration of agents generally associated with anterograde amnestic and sedative effects, such as benzodiazepines, is enhanced relative to a placebo condition. However, it is unclear whether this effect occurs in elderly individuals and if it is influenced by plasma drug levels, baseline cognitive function, or genetic factors such as the APOE e-4 allele, that may modulate drug-induced cognitive toxicity. OBJECTIVES: To determine if acute oral doses of lorazepam (0.5 mg, 1 mg) produced RF in elderly individuals exposed to interference tasks, and the variables associated with RF. MATERIALS AND METHODS: Sixty-four cognitively intact and highly educated (>12 years) older adults (mean age, 66.09 years) participated in a placebo-controlled double-blind crossover study. The Buschke Selective Reminding Test was used to assess RF and amnestic effects for verbal memory. Self-ratings of mood states were also obtained. RESULTS: Lorazepam administration resulted in significant dose-dependent RF, i.e., better recall of pre-drug word lists compared to placebo [F(1,63)= 15.358; p<0.001 and F(1,63)= 46.163; p<0.001 for 0.5 and 1 mg lorazepam, respectively]. Also, more of the pre-drug words were recalled in the 1.0-mg-lorazepam condition relative to the 0.5-mg-lorazepam condition [F(1,63)=29.498; p<0.001]. In both the 0.5 and 1 mg lorazepam conditions, participants who exhibited high RF experienced significantly greater lorazepam-induced memory impairments over time [F(3,61)=2.901; p<0.05; F(3,61)=2.698; p<0.05; 0.5 and 1 mg lorazepam, respectively]. Also, in the 1-mg-lorazepam condition, participants who exhibited high RF reported significantly greater drowsiness relative to participants who showed less RF [t(62)=-2.521; p<0.05]. RF was not significantly associated with age, the APOE epsilon4 allele, years of education, global cognitive status, vocabulary scores, or a memory index score. CONCLUSION: In healthy elderly, acute oral lorazepam administration resulted in dose-dependent RF, which was associated with greater anterograde amnestic and sedative effects
— id: 69569, year: 2006, vol: 185, page: 487, stat: Journal Article,

The effect of mifepristone (RU 486) on plasma cortisol in Alzheimer's disease
Pomara, Nunzio; Hernando, Raymundo T; de la Pena, Corazon B; Sidtis, John J; Cooper, Thomas B; Ferris, Steven
2006 May;31(5):585-588, Neurochemical research
The glucocorticoid receptor (GR) antagonist mifepristone (RU-486) has been reported to increase early morning plasma ACTH/cortisol in diverse non-demented populations. This pilot study examined the cortisol response to RU 486 in patients with Alzheimer's disease (AD), a condition associated with abnormalities in various aspects of the hypothalamic-pituitary-adrenal (HPA) axis. Nine AD subjects were randomized in a placebo-controlled parallel study: 4 in the placebo group and 5 in the RU 486 group. Subjects received oral doses of RU 486 (200 mg) or placebo daily for 6-weeks. Morning plasma cortisol was determined at baseline, at 12 h following the first study drug dose, and weekly thereafter. RU 486 resulted in a significant increase in cortisol levels [F(1,6)=65.32; P<0.001]. The magnitude of this increase grew over the course of the study [F(1,6)=63.17; P<0.001], was not related to cortisol suppression after dexamethasone and appeared greater than that reported in the literature in younger populations in response to the same drug regimen. However, further studies with age-matched controls should be done to determine possible AD related changes in this response
— id: 69567, year: 2006, vol: 31, page: 585, stat: Journal Article,

Pathophysiology of Alzheimer's disease
Imbimbo, Bruno P; Lombard, Jay; Pomara, Nunzio
2005 Nov;15(4):727-53, ix, Neuroimaging clinics of North America
Tremendous progress has been made in understanding the processes of the Alzheimer's disease (AD) cascade, laying the groundwork for improvements in diagnosis and treatment. Advancement has been made in understanding the genetic basis of AD, with identification of causative genes for early-onset familial AD, and the role of the polymorphism of the APOE gene in the late-onset form of the disease. Understanding cerebral degeneration and accumulation of beta-amyloid has generated hopes for discovery of disease-modifying treatments. Progress is needed in understanding the mechanisms that link beta-amyloid accumulation and neuronal death. The next 5 years will be crucial in this respect
— id: 69570, year: 2005, vol: 15, page: 727, stat: Journal Article,

Abnormal white matter integrity in healthy apolipoprotein E epsilon4 carriers
Nierenberg, Jay; Pomara, Nunzio; Hoptman, Matthew J; Sidtis, John J; Ardekani, Babak A; Lim, Kelvin O
2005 Aug 22;16(12):1369-1372, Neuroreport
Apolipoprotein E epsilon4 is a major genetic risk factor for Alzheimer's disease, but the neurobiological basis for this risk is unknown. We used diffusion tensor imaging to measure diffusion anisotropy in the parahippocampal gyrus white matter in healthy elderly apolipoprotein E epsilon4 carriers and noncarriers. We also measured volumes of the lateral ventricles and temporal horns as proxies of cerebral atrophy. The epsilon4 carriers (n=14) showed significantly lower fractional anisotropy and higher radial diffusivity in the parahippocampal white matter 15 mm below the anterior commissure-posterior commissure plane than noncarriers (n=15). No group differences in ventricular volumes were found, nor were diffusion tensor imaging measures modulated by ventricular volumes. Diffusion tensor imaging may be sufficiently sensitive to detect preclinical brain changes related to Alzheimer's disease
— id: 60837, year: 2005, vol: 16, page: 1369, stat: Journal Article,

Efficacy of memantine on cognition in mild to moderate Alzheimer's disease
Pomara, N; Ott, B; Peskind, E; Resnick, M
2005 JAN 1 ;17(1):210-211, International psychogeriatrics
— id: 62387, year: 2005, vol: 17, page: 210, stat: Journal Article,

Screaming and physical aggression in nursing homes
Pomara, Nunzio; Volavka, Jan; Czobor, P'al; Hernando, Raymundo; Sidtis, John J
2005 Jun;13(6):539-540, American journal of geriatric psychiatry
— id: 60839, year: 2005, vol: 13, page: 539, stat: Journal Article,

Sex-related elevation in cortisol during chronic treatment with alprazolam associated with enhanced cognitive performance
Pomara, Nunzio; Willoughby, Lisa M; Ritchie, James C; Sidtis, John J; Greenblatt, David J; Nemeroff, Charles B
2005 Nov;182(3):414-419, Psychopharmacology
OBJECTIVE: There is evidence of more widespread use and abuse of benzodiazepines (BZPs) among elderly women. However, factors underlying this observation are poorly understood but could be related to more intense withdrawal reactions, which are a major risk factor for continued BZP use. We previously reported elevations in interdose morning plasma cortisol levels in healthy elderly individuals after chronic treatment with alprazolam, possibly consistent with increased hypothalamic-pituitary-adrenal (HPA) axis activity and drug withdrawal. In this study, we examined sex-related differences in this population. METHOD: Twenty-five cognitively intact healthy elderly (13 women and 12 men) participated in a parallel, double-blind, placebo-controlled study that included a group that received acute and chronic (3 weeks) treatment with alprazolam (0.5 mg b.i.d.). RESULTS: Elderly women, but not men, experienced significant elevations in interdose morning plasma cortisol levels over 3 weeks of chronic treatment with alprazolam (0.5 mg b.i.d.) compared to placebo. In addition, higher morning plasma cortisol levels were significantly associated with better cognitive performance but not with higher plasma drug levels or greater degree of tolerance development to an acute alprazolam challenge. CONCLUSION: Elderly females experienced a greater interdose activation of the HPA axis during treatment with therapeutic doses of alprazolam than men, which could be related to drug withdrawal
— id: 60838, year: 2005, vol: 182, page: 414, stat: Journal Article,

Cortisol response to diazepam: its relationship to age, dose, duration of treatment, and presence of generalized anxiety disorder
Pomara, Nunzio; Willoughby, Lisa M; Sidtis, John J; Cooper, Thomas B; Greenblatt, David J
2005 Feb;178(1):1-8, Psychopharmacology
OBJECTIVE: Acute diazepam administration has been shown to decrease plasma cortisol levels consistent with decreased activity of the hypothalamic-pituitary-adrenal axis, especially in individuals experiencing stress. However, the effects of chronic diazepam treatment on cortisol have been less studied, and the relationship to age, anxiety, duration of treatment, and dose are not well understood.METHOD: This double-blind placebo-controlled study examined acute and chronic effects of diazepam on plasma cortisol levels in young (19-35 years) and elderly (60-79 years) individuals with and without generalized anxiety disorder (GAD). Subjects received single oral challenges of placebo or diazepam (2.5 mg or 10 mg) in a placebo-controlled cross-over design, followed by 3 weeks of chronic daily treatment with 2.5 mg or 10 mg diazepam or placebo taken at 10 p.m., and then by a final acute challenge with a single oral dose of the same study medication received during chronic treatment.RESULTS: The elderly experienced significant reductions in plasma cortisol levels compared to placebo both in the initial challenge and during chronic treatment, but the young did not. However, cortisol response to drug was comparable in both groups. Final challenge did not produce any significant cortisol effects in either group and the cortisol response in the elderly was significantly reduced compared to the initial challenge. GAD status was not a factor in plasma cortisol responses to diazepam.CONCLUSIONS: Diazepam reduced cortisol both acutely and during chronic treatment, but not during final challenge, consistent with some tolerance development. This effect was most apparent in the elderly compared with the young adults and was not modulated by GAD status or dosage, and was not related to drug effects on performance and on self-ratings of sedation and tension
— id: 48097, year: 2005, vol: 178, page: 1, stat: Journal Article,

Selective reductions in plasma Abeta 1-42 in healthy elderly subjects during longitudinal follow-up: a preliminary report
Pomara, Nunzio; Willoughby, Lisa M; Sidtis, John J; Mehta, Pankaj D
2005 Oct;13(10):914-917, American journal of geriatric psychiatry
OBJECTIVE: Longitudinal changes in plasma beta amyloid protein 1-42 and 1-40 (Abeta42 and Abeta40) levels and possible relationships with cognitive decline and apolipoprotein (APOE) genotype were studied in healthy elderly individuals. Methods: Authors determined cognitive level and plasma Abeta40 and Abeta42 levels twice, approximately 4 years apart, in 34 elderly subjects. Results: Analyses revealed a selective reduction in Abeta42 levels at follow-up, which were not modulated by the epsilon4 allele. Greater reductions and higher baseline plasma Abeta42 levels were associated with reductions in cognitive scores. Conclusions: Alterations in plasma Abeta42 levels may be associated with subtle cognitive decline in elderly subjects without dementia
— id: 60836, year: 2005, vol: 13, page: 914, stat: Journal Article,

Apolipoprotein E epsilon4 allele and lorazepam effects on memory in high-functioning older adults
Pomara, Nunzio; Willoughby, Lisa; Wesnes, Keith; Greenblatt, David J; Sidtis, John J
2005 Feb;62(2):209-216, Archives of general psychiatry
CONTEXT: The apolipoprotein E (APOE) epsilon4 allele has been implicated as a significant risk factor in the development of late-onset Alzheimer disease, but the evidence of cognitive sequelae in healthy individuals has been mixed. OBJECTIVE: To determine if the APOE epsilon4 allele increases susceptibility to lorazepam-induced verbal learning impairment in nondemented older adults. DESIGN: A placebo-controlled crossover design. SETTING: A community-based sample of subjects. PARTICIPANTS: Sixty-four cognitively intact and highly educated (>12 years) adults. Twenty-four subjects (mean age, 66.3 years) were carriers of an APOE epsilon4 allele (epsilon4 positive) and 40 (mean age, 66.0 years) were not (epsilon4 negative). INTERVENTIONS: All subjects received a single oral dose of placebo and lorazepam (0.5 and 1.0 mg) 1 week apart. MAIN OUTCOME MEASURE: We used the Buschke Selective Reminding Test to assess verbal learning during a 5-hour period after placebo or lorazepam administration. RESULTS: We found a time-related, dose-dependent effect of lorazepam, with long-term recall generally decreasing with higher doses of lorazepam at up to 2.5 hours. At 5 hours, the epsilon4-negative group showed significant improvement in long-term memory, but the epsilon4-positive group demonstrated a persistent deficit. Subsequent analysis revealed that the poor performance at 5 hours was found in an epsilon4-positive subgroup with lower baseline performance. CONCLUSIONS: In cognitively intact, older adults, the effect of the APOE epsilon4 allele is not necessarily seen in the immediate response to benzodiazepine challenge. Rather, the APOE epsilon4 allele appears to affect the carrier's ability to recover from a cognitive challenge in a normal fashion, at least in a subgroup of subjects with relatively low baseline performance. This suggests that although carrying an APOE epsilon4 allele increases the risk for cognitive toxic effects, allele status alone is not a sufficient predictor of such effects. Studying the response to and the recovery from cognitive challenges may provide insights into the role of the APOE epsilon4 allele and its interaction with other factors in the development of Alzheimer disease and other age-related cognitive problems
— id: 48095, year: 2005, vol: 62, page: 209, stat: Journal Article,

Increased plasma A beta 1-42 in geriatric depression
Reynolds, C; Willoughby, L; Mulsant, B; Metha, P; Pollock, B; Pomara, N
2005 JAN 1 ;17(1):128-129, International psychogeriatrics
— id: 62386, year: 2005, vol: 17, page: 128, stat: Journal Article,

Memantine monotherapy is effective and safe for the treatment of mild to moderate Alzheimer's disease: A randomized controlled trial
Peskind, ER; Potkin, SG; Pomara, N; Ott, BR; McDonald, S; Xie, Y; Gergel, I
2004 OCT ;14(3):S332-S332, European neuropsychopharmacology
— id: 50157, year: 2004, vol: 14, page: S332, stat: Journal Article,

Memantine monotherapy is effective and safe for the treatment of mild to moderate Alzheimer's disease: A randomized controlled trial
Peskind, ER; Potkin, SG; Pomara, N; Ott, BR; McDonald, S; Xie, Y; Gergel, I
2004 JUN ;7(3):S207-S207, International journal of neuropsychopharmacology
— id: 50486, year: 2004, vol: 7, page: S207, stat: Journal Article,

Plasma amyloid beta 1-42 levels in geriatric depression: A pilot study
Pomara, N; Doraiswamy, PM; Willoughby, L; Mehta, PD; Pollock, BG
2004 DEC ;29(2):S202-S202, Neuropsychopharmacology
— id: 50150, year: 2004, vol: 29, page: S202, stat: Journal Article,

Memantine, monotherapy is effective and safe for the treatment of mild to moderate Alzheimer's disease: A randomized controlled trial
Pomara, N; Peskind, ER; Potkin, SG; McDonald, S; Xie, Y; Gergel, I
2004 JUL ;25(10):S19-S19, Neurobiology of aging
— id: 47709, year: 2004, vol: 25, page: S19, stat: Journal Article,

Plasma A beta 42 in healthy elderly during follow-up: Relationship to cognitively decline and APOE genotype
Pomara, N; Willoughby, LM; Sidtis, JJ; Mehta, PD
2004 JUL ;25(10):S352-S352, Neurobiology of aging
— id: 47733, year: 2004, vol: 25, page: S352, stat: Journal Article,

Selective reductions in plasma A beta 42 in healthy elderly during follow-up: Relationship to cognitively decline and APOE genotype
Pomara, N; Willoughby, LM; Sidtis, JJ; Mehta, PD
2004 APR 15 ;55(5):55S-55S, Biological psychiatry
— id: 46647, year: 2004, vol: 55, page: 55S, stat: Journal Article,

Effects of acute lorazepam administration on aminergic activity in normal elderly subjects: relationship to performance effects and apolipoprotein genotype
Pomara, Nunzio; Willoughby, Lisa M; Hashim, Audrey; Sershen, Henry; Sidtis, John J; Wesnes, Keith; Greenblatt, David J; Lajtha, Abel
2004 Aug;29(7):1391-1398, Neurochemical research
The effects of acute lorazepam challenges on plasma (p) HVA, MHPG, and 5-HIAA, and their relationship to drug-induced cognitive and motor deficits and the apolipoprotein (APOE)-epsilon4 allele were examined. Eighteen healthy elderly (8 epsilon4 carriers) received placebo or acute oral lorazepam doses (0.5 mg or 1 mg) in random sequence, 1-week apart. Cognitive assessment and plasma levels of pHVA, pMHPG, and p5-HIAA were determined at baseline and at 1, 2.5, and 5 h postchallenge. There was no drug-to-placebo difference in monoamine levels and no consistent relationship between changes in monoamine levels and cognitive performance, regardless of epsilon4 status. However, the 1.0 mg dose increased p5-HIAA in epsilon4 carriers, whereas it caused a reduction in noncarriers. Higher baseline pMHPG and p5-HIAA levels were associated with better baseline memory. The epsilon4 allele may modulate the effect of lorazepam on p5-HIAA, but further studies are needed to confirm this finding and elucidate its possible significance
— id: 46010, year: 2004, vol: 29, page: 1391, stat: Journal Article,

Interdose elevation in plasma cortisol during chronic treatment with alprazolam but not lorazepam in the elderly
Pomara, Nunzio; Willoughby, Lisa M; Ritchie, James C; Sidtis, John J; Greenblatt, David J; Nemeroff, Charles B
2004 Mar;29(3):605-611, Neuropsychopharmacology
Benzodiazepines (BZPs) have been shown to reduce hypothalamic-pituitary-adrenal (HPA) axis activity acutely in normal humans. In contrast, the effects of chronic BZP treatment on the HPA axis have not been well studied, especially in the geriatric population. This study examined the acute and chronic effects (3 weeks) of alprazolam and lorazepam on plasma cortisol in 68 subjects (60-83 years) who received 0.25 or 0.50 mg b.i.d. alprazolam, or 0.50 or 1.0 mg b.i.d. lorazepam, or placebo orally according to a randomized, double-blind, placebo-controlled parallel design. Memory assessment and blood samples for plasma cortisol were obtained prior to the morning dose on days 0, 7, 14, and 21, and at 1, 2.5, and 5 h postdrug on days 0 and 21. Assessments of anxiety and depression were carried out at days 0, 7, 14, and 21 before drug administration. Plasma cortisol was affected compared to placebo only by the 0.5 mg alprazolam dose. During the first and the last day of treatment, there was a significant drop in cortisol at 2.5 h after alprazolam compared to placebo. The predose cortisol levels increased significantly during chronic alprazolam treatment, and correlations were found between these cortisol changes and changes in depression, anxiety, and memory scores. These findings suggest that even a short period of chronic treatment with alprazolam, but not lorazepam, may result in interdose HPA axis activation in the elderly, consistent with drug withdrawal. If confirmed, this effect may contribute to an increased risk for drug escalation and dependence during chronic alprazolam treatment
— id: 44701, year: 2004, vol: 29, page: 605, stat: Journal Article,

Baseline plasma GABA: its relationship to the adverse effects of acute lorazepam administration on cognition in the elderly
Pomara, Nunzio; Willoughby, Lisa M; Sidtis, John J; Doraiswamy, P Murali; Wesnes, Keith A; Cooper, Thomas B; Greenblatt, David J
2004 Dec;29(12):2311-2315, Neurochemical research
The GABA system is an active target for drugs to treat a variety of disorders and the availability of an indirect measure of central GABA activity would not only enhance psychiatric research, but also permit assessment of the pharmacodynamic effects of drugs designed to act on this system. The relationships between plasma baseline pre-drug GABA concentrations and cognitive impairments induced by an acute oral dose of lorazepam (0.5 and 1.0 mg) were investigated in 22 healthy elderly individuals. Partial correlations controlling for plasma lorazepam concentrations revealed no significant relationship between baseline plasma GABA levels and lorazepam-induced impairments on tests of cognitive functioning. Plasma GABA concentration does not appear to be a useful marker of susceptibility to benzodiazepine-induced cognitive toxicity in the elderly. Other approaches to estimating central GABA activity should be pursued
— id: 48096, year: 2004, vol: 29, page: 2311, stat: Journal Article,

Increased anticholinergic challenge-induced memory impairment associated with the APOE-epsilon4 allele in the elderly: a controlled pilot study
Pomara, Nunzio; Willoughby, Lisa M; Wesnes, Keith; Sidtis, John J
2004 Mar;29(2):403-409, Neuropsychopharmacology
The degree to which elderly adults experience cognitive impairments from centrally acting anticholinergic drugs is variable, but the cause of this variability is unknown. The present study examined the epsilon4 allele as a possible modulator of the effects of trihexyphenidyl hydrochloride (Artane( trade mark )), an anticholinergic drug, on memory functioning. Of the 24 cognitively intact, elderly participants (age range 62-76), 12 who possessed the epsilon4 allele, participated in a double-blind, randomized, placebo-controlled, crossover, three-way study. All participants were tested after receiving a single oral dose of trihexyphenidyl (1 or 2 mg) or placebo, with a 7-day washout period between sessions. Memory and psychomotor tests were administered at baseline, and at 1, 2.5, and 5 h post-treatment. Results showed that participants with the epsilon4 allele demonstrated significant impairments in delayed recall after both 1 and 2 mg doses of trihexyphenidyl while the non-epsilon4 group did not. Additionally, while acute administration of the 2 mg dose significantly impaired total recall in both epsilon4 and non-epsilon4 carriers, the epsilon4 carriers showed a more persistent impairment. These findings held when participants with the epsilon2 allele were excluded from the analyses. The epsilon4 groups did not differ with respect to psychomotor performance or plasma drug levels. These results provide evidence suggesting that the epsilon4 allele plays a significant role in increasing cognitive sensitivity to trihexyphenidyl and that a temporal component of memory consolidation may be especially vulnerable. A larger study is warranted to confirm these preliminary findings
— id: 46240, year: 2004, vol: 29, page: 403, stat: Journal Article,

Ginkgo and memory
Doraiswamy, P Murali; Pomara, Nunzio
2003 Feb 5;289(5):547-547, JAMA
— id: 44703, year: 2003, vol: 289, page: 547, stat: Journal Article,

Lorazepam effects on memory in high-functioning elderly: Relationship to APOE-epsilon 4 allele
Pomara, N; Willoughby, L; Wesnes, K; Greenblatt, DJ; Sidtis, J
2003 APR 15 ;53(8):87S-87S, Biological psychiatry
— id: 37113, year: 2003, vol: 53, page: 87S, stat: Journal Article,

Therapeutic implications of HPA axis abnormalities in Alzheimer's disease: review and update
Pomara, Nunzio; Greenberg, William M; Branford, Michael D; Doraiswamy, P Murali
2003 Spring;37(2):120-134, Psychopharmacology bulletin
The adaptive and maladaptive roles of the hypothalamic-pituitary-adrenal (HPA) axis in stressful conditions and in disorders such as major depression, posttraumatic stress disorder, and Cushing's syndrome, have been the subject of substantial, ongoing study. In particular, HPA disturbances have been associated with memory impairments, and hypercortisolemic conditions with atrophy of the hippocampus, a limbic structure closely associated with declarative memory. Recent discoveries support a more complicated picture of HPA axis function and pathology in acquiring, retrieving, and consolidating new memories. These findings include: the existence of an 'inverted U-shaped relationship' between stimulation of brain glucocorticoid receptors and memory performance; that distinct areas of the hippocampus have been found to respond differently to cortisol stimulation; and that hippocampal atrophy has been found to be potentially reversible in some conditions, although whether such atrophy is a cause or effect of these pathological conditions is currently unclear. More longitudinal studies of HPA axis function in aging normal individuals, those with mild cognitive impairment,and individuals with Alzheimer' disease, examining pertinent variables such as APOEe-4 status, are needed to help clarify these new findings. Antiglucocorticoid agents appear to have therapeutic value in particular conditions. These results are relevant for understanding and treating memory dysfunction in individuals with Alzheimer's disease, a disorder prominently and invariably characterized by early hippocampal lesions and memory impairment. Given the burden of this disease, we feel it timely to encourage controlled trials of antiglucocorticoid agents in the treatment of mild cognitive impairment and Alzheimers disease
— id: 44702, year: 2003, vol: 37, page: 120, stat: Journal Article,

Does increased platelet release of Abeta peptide contribute to brain abnormalities in individuals with depression?
Pomara, Nunzio; Murali Doraiswamy, P
2003 May;60(5):640-643, Medical hypotheses
Increased platelet activation with release of procoagulant factors from their alpha granules has been demonstrated in individuals with major depression. Platelet activation has also been shown to be associated with release of beta-amyloid peptides, which have been implicated in Alzheimer's disease. Thus, we are hypothesizing that sustained elevations of Abeta peptides might occur in individuals with recurrent depression. We further hypothesize that such elevations contribute to brain abnormalities in depressed individuals through the formation of neurotoxic oligomeric forms of Abeta peptides and amyloid deposition. We also propose that increased amyloid Abeta peptides from platelet activation may be a mechanism underlying the increased risk for cognitive impairment in nondepressed patients who have other reasons for such activation. If true, our hypothesis would imply that platelet inhibitors may have a role in preventing or delaying the neuronal consequences of disorders characterized by activated platelets
— id: 39238, year: 2003, vol: 60, page: 640, stat: Journal Article,

Reduced frontal white matter integrity in cocaine dependence: a controlled diffusion tensor imaging study
Lim, Kelvin O; Choi, Steven J; Pomara, Nunzio; Wolkin, Adam; Rotrosen, John P
2002 Jun 1;51(11):890-895, Biological psychiatry
BACKGROUND: In vivo magnetic resonance studies have found that cocaine dependence is associated with T2 signal hyperintensities and metabolite abnormalities in cerebral white matter (WM). Functional neuroimaging studies have suggested that chronic cocaine use is primarily associated with frontal lobe deficits in regional cerebral blood flow and brain glucose metabolism levels; however, the effects of cocaine dependence, if any, on frontal WM microstructure are unknown. Thus, we sought to examine the effects of cocaine dependence on frontal WM integrity. METHODS: Diffusion tensor imaging was employed to examine the WM integrity of frontal regions at four levels: 10 mm above, 5 mm above, 0 mm above, and 5 mm below the anterior commissure-posterior commissure (AC-PC) plane. The fractional anisotropy (FA) of 12 cocaine-dependent patients and 13 age-similar control subjects was compared. RESULTS: The cocaine-dependent patients had significantly reduced FA in the frontal WM at the AC-PC plane and a trend toward reduced FA at 5 mm below the AC-PC plane, suggestive of reduced WM integrity in these regions. CONCLUSIONS: These findings were consistent with the hypothesis that cocaine dependence involves alterations in orbitofrontal connectivity, which may be involved in the decision-making deficits seen in this disorder
— id: 32117, year: 2002, vol: 51, page: 890, stat: Journal Article,

Mifepristone (RU 486) for Alzheimers disease - Preliminary findings
Pomara, N; Doraiswamy, M; Tun, H; Ferris, SH
2002 Apr 15;51(8):219-, Biological psychiatry
— id: 27473, year: 2002, vol: 51, page: 219, stat: Journal Article,

Mifepristone (RU 486) for Alzheimer's disease - A pilot study
Pomara, N; Doraiswamy, PM; Tun, H
2002 Jul-Aug;23(1):316-, Neurobiology of aging
— id: 32410, year: 2002, vol: 23, page: 316, stat: Journal Article,

ApoE polymorphism and anticholinergic cognitive toxicity in the elderly
Pomara, N; Tun, H; Hernando, RT; de la Pena, CB; Cooper, TB; Wesnes, KA
2002 Jul-Aug;23(1):1486-, Neurobiology of aging
— id: 32428, year: 2002, vol: 23, page: 1486, stat: Journal Article,

Relationship between verbal and physical aggression in dementia: A pilot study
Pomara, N; Volavka, J; Czobor, P; Sidtis, JJ
2002 NOV ;63(11):1077-1077, Journal of clinical psychiatry
— id: 33280, year: 2002, vol: 63, page: 1077, stat: Journal Article,

Mifepristone (RU 486) for Alzheimer's disease
Pomara, Nunzio; Doraiswamy, P Murali; Tun, Hla; Ferris, Steven
2002 May 14;58(9):1436-1436, Neurology
— id: 27565, year: 2002, vol: 58, page: 1436, stat: Journal Article,

White matter abnormalities in HIV-1 infection: a diffusion tensor imaging study
Pomara N; Crandall DT; Choi SJ; Johnson G; Lim KO
2001 Feb 28;106(1):15-24, Psychiatry research
Diffuse white matter pallor is the most frequent neuropathological feature of HIV-1 infection and has been found to be particularly prominent in the advanced stages of the disease. The purpose of this study was to determine whether subtle white matter abnormalities can be detected in medically stable, ambulatory HIV-1 patients, in vivo, using diffusion tensor imaging (DTI). DTI is a magnetic resonance imaging (MRI) technique that is uniquely suited for the study of subtle white matter abnormalities. DTI was performed in six HIV-1 patients and nine controls. The two groups were similar in age. Abnormal fractional anisotropy was found in the white matter of the frontal lobes and internal capsules of the HIV-1 patients, in the absence of group differences in mean diffusivity, computed proton density, and computed T2. DTI may be more sensitive than conventional MRI methods for detecting subtle white matter disruptions in HIV-1 disease
— id: 23681, year: 2001, vol: 106, page: 15, stat: Journal Article,

Sex-related differences in nortriptyline-induced side-effects among depressed patients
Pomara N; Shao B; Choi SJ; Tun H; Suckow RF
2001 Jul;25(5):1035-1048, Progress in neuro-psychopharmacology & biological psychiatry
1. Men and women may differ in their pharmacokinetic responses to tricyclic antidepressants (TCAs), in a number of autonomic indices, and in various adrenergic receptor mediated responses. Emerging evidence also suggests that women may have a lower rate of serotonin synthesis in brain and a greater sensitivity to the depressant effects of tryptophan depletion, relative to men. However, sex-related differences in TCA-induced side-effects, including increases in heart rate (HR), dry mouth, constipation, and difficulty urinating, has not been systematically investigated. 2. The authors examined potential sex-related differences in the pattern of side-effects during treatment with nortriptyline (NT), a TCA that is still widely used. Seventy-eight healthy outpatients who met Research Diagnostic Criteria and DSM-III-R criteria for major depression participated in a double-blind, randomized parallel trial of NT versus placebo. 3. Each subject was acutely challenged with either placebo or 50 mg NT prior to and after a 6-week treatment with NT. NT doses were adjusted weekly to maintain therapeutic plasma levels. Patients were assessed at multiple time points to detect the presence of NT-induced side-effects. 4. The initial, single (50 mg) dose of NT significantly increased supine HR. Six-week treatment with NT was found to significantly increase supine and sitting HRs, irrespective of sex. In rechallenge with the single NT dose, there were no significant effects on HR. 5. When sex-related differences were examined, HR increases were greater in men than women during weeks 4 through 6 of the NT treatment, although no sex-related differences were present in plasma NT levels or metabolites. In addition, there was a significant NT to placebo difference in self-rated dry mouth for women during all 6-weeks of treatment, whereas men showed a significant NT-placebo difference during weeks 3 and 5. 6. The results suggest the presence of sex-related differences in elevated supine HR response during the course of 6-week NT treatment. Depressed men may be more susceptible to NT-induced increases in supine HR than women
— id: 23680, year: 2001, vol: 25, page: 1035, stat: Journal Article,

Risperidone in the treatment of elderly patients with psychotic disorders
Madhusoodanan S; Brecher M; Brenner R; Kasckow J; Kunik M; Negron AE; Pomara N
1999 Spring;7(2):132-138, American journal of geriatric psychiatry
The authors evaluated the safety, tolerability, and efficacy of risperidone in 103 elderly patients (mean age, 71 years) with schizophrenia (75%) or schizoaffective disorder (25%). Using the Extrapyramidal Symptoms Rating Scale (ESRS), Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression (CGI) scale, they conducted a prospective, open-label, 12-week trial in 14 psychiatric centers in the United States. Patients' symptoms were assessed at baseline and over a 12-week period. At endpoint, ESRS scores were significantly reduced, as were PANSS total and subscale scores. There were no clinically significant changes in electrocardiograms, laboratory test results, or vital signs. Risperidone was well tolerated and efficacious in elderly patients with schizophrenia or schizoaffective disorder
— id: 23682, year: 1999, vol: 7, page: 132, stat: Journal Article,

ApoE-epsilon 4 allele: Relationship to plasma amyloid beta and ApoE levels in normal elderly
Pomara, N; Shao, B; Wisniewski, T; Mehta, PD
1999 APR 15 ;45(8):274-49, Biological psychiatry
— id: 98321, year: 1999, vol: 45, page: 274, stat: Journal Article,

Decreases in plasma A beta 1-40 levels with aging in non-demented elderly with ApoE-epsilon 4 allele
Pomara N; Shao B; Wisniewski T; Mehta PD
1998 Dec;23(12):1563-1566, Neurochemical research
This report examines plasma amyloid beta proteins A beta 40 and A beta 42 and apolipoprotein E (apoE) levels and their relationships with age in non-demented older adults with (N = 32) or without the apoE-epsilon 4 allele (N = 94). A beta levels did not differ between the groups whereas the epsilon 4 allele was associated with a significant reduction in plasma apoE. In subjects with the epsilon 4 allele, increasing age was associated with significant reduction in plasma A beta 40. Subjects without the epsilon 4 allele showed a significant positive correlation between A beta 40 and A beta 42 levels. There was also a significant correlation between plasma A beta 40 and apoE levels in all subjects
— id: 7747, year: 1998, vol: 23, page: 1563, stat: Journal Article,

Benzodiazepine use and crash risk in older patients
Pomara N; Tun H; DaSilva D; Deptula D; Greenblatt DJ
1998 Jan 14;279(2):113-114, JAMA
— id: 23685, year: 1998, vol: 279, page: 113, stat: Journal Article,

The acute and chronic performance effects of alprazolam and lorazepam in the elderly: relationship to duration of treatment and self-rated sedation
Pomara N; Tun H; DaSilva D; Hernando R; Deptula D; Greenblatt DJ
1998 ;34(2):139-153, Psychopharmacology bulletin
We examined the acute performance and sedative effects of single high and low doses of alprazolam and lorazepam, both before and after chronic, 3-week b.i.d. treatment in elderly adults. The effects of chronic treatment also were examined in this parallel, double-blind, placebo-controlled study. Initial acute low doses significantly impaired total recall and increased intrusion errors. High doses also impaired delayed recall and critical flicker fusion threshold (CFF). Only chronic treatment with high-dose alprazolam increased intrusions and self-rated sedation. Single-dose rechallenge after chronic treatment was associated with significantly less impairment than the initial challenge in memory tasks but not in the discriminant reaction time (DRAT) task. For most memory measures, the development of tolerance was only partial; rechallenge still produced significant deficits in relation to placebo. The development of tolerance was task-specific and depended on drug type and dosage. Despite impairments in various memory functions, CFF, and DRAT, volunteers did not report significant drug-induced changes in sedation
— id: 23683, year: 1998, vol: 34, page: 139, stat: Journal Article,

ApoE-epsilon 4 allele and susceptibility to drug-induced memory impairment in the elderly
Pomara N; Tun H; Deptula D; Greenblatt DJ
1998 Apr;18(2):179-181, Journal of clinical psychopharmacology
— id: 23684, year: 1998, vol: 18, page: 179, stat: Journal Article,

Cerebrospinal fluid C3a increases with age, but does not increase further in Alzheimer's disease
Loeffler DA; Brickman CM; Juneau PL; Perry MF; Pomara N; Lewitt PA
1997 Sep-Oct;18(5):555-557, Neurobiology of aging
Complement activation is present in the brain in Alzheimer's disease (AD), and C1q concentrations are decreased in AD cerebrospinal fluid (CSF). To determine whether concentrations of other complement proteins are also altered in AD CSF, we measured concentrations of C3a and SC5b-9 in CSF from patients with probable AD (n = 19), normal aged controls (n = 11), and normal younger controls (n = 15). C3a concentrations were similar between AD and aged controls, but threefold higher than in younger controls (p < 0.05 vs. both groups). A similar pattern was found with SC5b-9, though the increase was only twofold and statistically significant only for AD vs. younger controls. These results suggest that an increased generation of complement proteins in localized areas of the AD brain does not result in elevated concentrations of these proteins in CSF, compared with age-matched controls. Increased C3a (and, to a lesser extent, SC5b-9) in aged controls may be due to increased complement activation, increased central nervous system production, and/or blood-brain barrier leakage of these proteins
— id: 23686, year: 1997, vol: 18, page: 555, stat: Journal Article,

Immunocytochemical detection of anti-hippocampal antibodies in Alzheimer's disease and normal cerebrospinal fluid
Loeffler DA; Juneau PL; Nguyen HU; Najman D; Pomara N; LeWitt PA
1997 Feb;22(2):209-214, Neurochemical research
Immunocytochemical staining was performed to investigate the presence of anti-hippocampal antibodies in cerebrospinal fluid (CSF) from patients with probable Alzheimer's disease (AD) (n = 19), aged normal controls (n = 9), and young normal controls (n = 10). Marked staining of neurons in the granule cell layer of the dentate gyrus and in pyramidal neurons in CA1-3 of the rat hippocampus was observed in 5 AD CSF samples (26%), 1 aged control sample (11%), and 1 young control sample (10%). These differences were not statistically significant. One of the immunoreactive AD CSF specimens also contained high concentrations of C5b-9, the membrane attack complex. The infrequent occurrence of anti-hippocampal antibodies in AD CSF, and the detection of similar immunoreactivity in control CSF specimens, suggest that these antibodies are unlikely to play a role in the neurodegenerative process in most individuals with AD. However, elevated C5b-9 concentration in an AD CSF specimen with marked immunoreactivity to hippocampal neurons suggests the possibility that anti-neuronal antibodies may contribute to complement activation in some AD patients
— id: 23687, year: 1997, vol: 22, page: 209, stat: Journal Article,

Reduced heart rate response to nortriptyline in females with unipolar depression
Pomara, N; Deptula, D; Nolan, K; Tun, H; Singh, R; Leviste, F; Cooper, TB
1996 APR 1 ;39(7):427-427, Biological psychiatry
— id: 52983, year: 1996, vol: 39, page: 427, stat: Journal Article,

Differential effects of alprazolam and lorazepam on plasma cortisol in normal elderly
Pomara, N; Deptula, D; Nolan, K; Tun, H; Singh, R; Leviste, F; Ritchie, J; Greenblatt, DJ; Nemeroff, CB
1996 APR 1 ;39(7):428-428, Biological psychiatry
— id: 52984, year: 1996, vol: 39, page: 428, stat: Journal Article,

Transient elevations in pancreatic enzymes in response to a cholinesterase inhibitor
Pomara N; Citrome L
1995 Oct;18(5):464-465, Clinical neuropharmacology
— id: 23688, year: 1995, vol: 18, page: 464, stat: Journal Article,

Scopolamine-induced impairment as a potential predictor of Alzheimer's disease in individuals with Apolipoprotein E type 4 alleles
Pomara N; Nolan K; Halpern G
1995 Dec;20(12):1519-1520, Neurochemical research
— id: 18206, year: 1995, vol: 20, page: 1519, stat: Journal Article,

Detecting Alzheimer's disease
Pomara N; Sitaram N
1995 Mar 17;267(5204):1579-1580, Science
— id: 23689, year: 1995, vol: 267, page: 1579, stat: Journal Article,

THE EFFECT OF NORTRIPTYLINE ON VERBAL RECALL
POMARA, N; NOLAN, K; DEPTULA, D; PESELOW, E; COOPER, TB
1995 MAY 1 ;37(9):611-611, Biological psychiatry
— id: 87283, year: 1995, vol: 37, page: 611, stat: Journal Article,

Caregivers and stress-related neurotransmitter changes
Chou, James C.-Y; Deptula, Dennis; Singh, Rajkumar; Pomara, Nunzio
Stress effects on family caregivers of Alzheimer's patients: Research and interventions New York, NY, US: Springer Publishing Co, 1994,
(from the chapter) the identification of neurotransmitter changes in caregivers [of Alzheimer's disease (AD) patients] may provide information about how the brain responds to chronic stress and shed light on etiologic theories of stress-related mental disorders / present [the authors'] findings of increased cerebrospinal fluid (CSF) gamma-aminobutyric acid (GABA) in caregivers of AD patients / review animal and human studies of neurotransmitter changes associated with stress focusing on GABA / describe possible neurotransmitter mechanisms for increased CSF GABA in caregivers / discuss implications for future research in this area /// norepinephrine / epinephrine / corticotropin releasing factor / serotonin / dopamine / acetylcholine / glycine / controllable versus uncontrollable stress
— id: 4794, year: 1994, vol: , page: 93, stat: Chapter,

Ceruloplasmin is increased in cerebrospinal fluid in Alzheimer's disease but not Parkinson's disease
Loeffler DA; DeMaggio AJ; Juneau PL; Brickman CM; Mashour GA; Finkelman JH; Pomara N; LeWitt PA
1994 Fall;8(3):190-197, Alzheimer disease & associated disorders
Although the pathophysiology of Alzheimer's disease (AD) and Parkinson's disease (PD) is unknown, altered brain antioxidative mechanisms have been found in both disorders. Ceruloplasmin (CP) and transferrin (TF) interact to limit concentrations of free ferrous iron (Fe2+), and thus play an important role in antioxidant defense in serum; both proteins are also produced in brain, where their significance as antioxidants is unknown. We quantified concentrations of CP and TF by immunoassay in AD (n = 17) and PD (n = 12) cerebrospinal fluid (CSF) to determine whether these proteins could serve as disease markers. CP was increased versus aged normal subjects (n = 11) in AD (p < 0.05) but not PD CSF, whereas TF concentrations did not differ between groups. CP levels have been reported to be elevated in some brain regions in AD, and increased CP in AD CSF may reflect this finding. Systemic inflammation and oxidative stress are major factors stimulating hepatic CP synthesis, and it remains to be determined whether increased CP concentrations in AD CSF and brain follow from similar mechanisms
— id: 23690, year: 1994, vol: 8, page: 190, stat: Journal Article,

CSF CONCENTRATIONS OF CRF IN ALZHEIMERS-DISEASE AND NORMAL-PRESSURE HYDROCEPHALUS
POMARA, N; BISSETTE, G; GOLOMB, J; TARSHISH, C; INCE, C; DESIMONE, P; FERRIS, S; DELEON, M
1994 JUL ;15(7):S121-S121, Neurobiology of aging
— id: 52409, year: 1994, vol: 15, page: S121, stat: Journal Article,

Aging, emotional states, and memory
Deptula D; Singh R; Pomara N
1993 Mar;150(3):429-434, American journal of psychiatry
OBJECTIVE: This study compared the relation between negative mood states and memory in young and elderly subjects. METHOD: Forty-five normal, healthy young volunteers (ages 19-35 years) and 45 normal, healthy elderly volunteers (ages 60-78 years) were administered a verbal list-learning task and self-rated scales of affective states. RESULTS: The elderly group, but not the young group, consistently exhibited significant correlations between their performance on verbal recall measures and their ratings of their anxiety, depression, and withdrawal; i.e., within the elderly group, higher levels of negative affective states were associated with poorer memory. CONCLUSIONS: These findings indicate that aging modulates the relation between emotional state and memory functions, and they are consistent with the hypothesis that the elderly are more vulnerable than the young to the adverse effects of negative emotional states on memory. Therefore, even in normal elderly individuals without diagnosable psychopathology, negative affective states (such as anxiety and depression) may interfere with memory functioning
— id: 23691, year: 1993, vol: 150, page: 429, stat: Journal Article,

EFFECT OF NICOTINE AND YOHIMBINE ON THE RELEASE OF [H-3] NOREPINEPHRINE FROM RAT HIPPOCAMPAL SLICES
ZELLES, T; SERSHEN, H; LAJTHA, A; POMARA, N; VIZI, ES
1993 ;61(8):S27-S27, Journal of neurochemistry
— id: 115503, year: 1993, vol: 61, page: S27, 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,

Glutamate and other CSF amino acids in Alzheimer's disease
Pomara N; Singh R; Deptula D; Chou JC; Schwartz MB; LeWitt PA
1992 Feb;149(2):251-254, American journal of psychiatry
The authors compared CSF amino acid levels of 10 patients with mild to moderate dementia and probable Alzheimer's disease who had never received antidepressant or neuroleptic medication with those of 10 normal subjects of similar age. The Alzheimer's patients had significantly higher levels of CSF glutamate. This finding was not related to age, sex, or severity of dementia. Elevated CSF glutamate may reflect greater glutamatergic activity early in the course of Alzheimer's disease. The authors speculate that the excitotoxic effects of glutamate may contribute to progressive neuronal loss in Alzheimer's disease
— id: 23693, year: 1992, vol: 149, page: 251, stat: Journal Article,

Increased CSF HVA response to arecoline challenge in Alzheimer's disease
Pomara N; Stanley M; LeWitt PA; Galloway M; Singh R; Deptula D
1992 ;90(1):53-65, Journal of neural transmission
The effects of the muscarinic agonist, arecoline, on the concentration of homovanillic acid (HVA) in the cerebrospinal fluid of patients with Alzheimer's disease (AD) and controls were examined. Patients and controls received intravenous infusions of arecoline and a lumbar puncture was performed four hours after the infusion began. Arecoline induced a significant increase in the concentration of HVA in cerebrospinal fluid of Alzheimer's disease patients (p < .01) but not in controls. The differential HVA response to a muscarinic agonist in Alzheimer's disease is suggestive of an alteration in muscarinic receptor response. This finding may have potential implications for the pathophysiology and treatment of Alzheimer's disease
— id: 23694, year: 1992, vol: 90, page: 53, stat: Journal Article,

Pretreatment postural blood pressure drop as a possible predictor of response to the cholinesterase inhibitor velnacrine (HP 029) in Alzheimer's disease
Pomara N; Deptula D; Singh R
1991 ;27(3):301-307, Psychopharmacology bulletin
The failure of cholinesterase inhibitors to produce noticeable improvement in about half of patients with Alzheimer's disease (AD) may result from heterogeneity of neurotransmitter abnormalities in this disorder. This study examined whether pretreatment postural blood pressure (BP) drop, which presumably reflects sympathetic response, differed in patients who were responders or nonresponders to the cholinesterase inhibitor, HP 029. Twenty-three AD patients completed a double-blind dose-finding phase of a clinical trial in which four doses of HP 029 and placebo were administered. Evaluation for efficacy occurred after 7 days of treatment at each dose. Of the 23 patients, 12 were classified as responders in the dose-ranging phase of the study. Nonresponders demonstrated significantly greater decreases in pretreatment systolic postural BPs when going from a supine to sitting position than did responders. The greater postural BP drop in nonresponders may identify a subgroup of AD patients that responds poorly to cholinesterase inhibitors
— id: 23695, year: 1991, vol: 27, page: 301, stat: Journal Article,

Cognitive toxicity of benzodiazepines in the elderly
Pomara, Nunzio; Deptula, Dennis; Singh, Rajkumar; Monroy, Cherry Ann
Anxiety in the elderly: Treatment and research New York, NY, US: Springer Publishing Co, 1991,
(from the chapter) will selectively review studies of adverse effects of benzodiazepines on cognitive and psychomotor functions with particular focus on the elderly /// the development of benzodiazepines represents a psychopharmacological milestone in the treatment of anxiety and insomnia / despite their efficacy and relative safety, the benzodiazepines' addictive and abuse potential warrants caution in prescribing these drugs for extended periods / these drugs have adverse effects on memory, attention and psychomotor functions which may impair a patient's ability to perform their normal routine /// the effects of benzodiazepines in the young / the effects of benzodiazepines in the elderly / comparison of the performance effects on young and elderly / the effects of benzodiazepines in the anxious / preliminary findings
— id: 4795, year: 1991, vol: , page: 175, stat: Chapter,

Effects of antidepressants on human performance: a review
Deptula D; Pomara N
1990 Apr;10(2):105-111, Journal of clinical psychopharmacology
Despite widespread use of antidepressants, major gaps remain in our knowledge of the effects of antidepressants on human performance. While most single-dose studies with normal subjects have suggested that the more sedating tricyclic antidepressants tend to produce impairment, the effects of antidepressant treatment in clinical populations have been less thoroughly examined, with both drug-induced impairment and improvement reported. This review suggests that factors such as age, diagnosis, drug plasma concentration, and length of treatment need to be explored to establish the effects of antidepressants on performance in clinical populations
— id: 23696, year: 1990, vol: 10, page: 105, stat: Journal Article,

Equivalence of five forms of the Selective Reminding Test in young and elderly subjects
Deptula D; Singh R; Goldsmith S; Block R; Bagne CA; Pomara N
1990 Dec;67(3 Pt 2):1287-1295, Psychological reports
This study evaluated the equivalence of five forms of the Selective Reminding Test, a widely used measure of verbal learning, 45 normal young and 45 normal elderly subjects were randomly administered three of the five test forms on three separate sessions. The five forms generally correlated well with one another and were of comparable difficulty, suggesting adequate test equivalence. Four of the five forms were particularly well matched
— id: 14269, year: 1990, vol: 67, page: 1287, stat: Journal Article,

POSTURAL BLOOD-PRESSURE DROP AS A POSSIBLE PREDICTOR OF RESPONSE TO CHOLINERGIC THERAPY IN ALZHEIMERS-DISEASE
POMARA N; DEPTULA D; SINGH R; DESIMONE P
1990 May-Jun;11(3):343-343, Neurobiology of aging
— id: 130874, year: 1990, vol: 11, page: 343, stat: Journal Article,

ALTERATIONS IN EXCITATORY AMINO-ACID-CONCENTRATIONS IN CSF OF PATIENTS WITH ALZHEIMERS-DISEASE
POMARA N; DEPTULA D; SINGH R; LEWITT PA; BANAYSCHWARTZ M
1990 May-Jun;11(3):287-287, Neurobiology of aging
— id: 130875, year: 1990, vol: 11, page: 287, stat: Journal Article,

CSF GABA in caregiver spouses of Alzheimer patients
Pomara N; Deptula D; Galloway MP; LeWitt PA; Stanley M
1989 Jun;146(6):787-788, American journal of psychiatry
The authors studied CSF gamma-aminobutyric acid (GABA) in 14 Alzheimer patients and nine age-matched normal subjects. The five normal subjects who were wives of the demented patients had higher CSF GABA concentrations than the four normal subjects without demented spouses
— id: 23698, year: 1989, vol: 146, page: 787, stat: Journal Article,

Effects of diazepam on recall memory: relationship to aging, dose, and duration of treatment
Pomara N; Deptula D; Medel M; Block RI; Greenblatt DJ
1989 ;25(1):144-148, Psychopharmacology bulletin
— id: 23699, year: 1989, vol: 25, page: 144, stat: Journal Article,

Possible muscarinic supersensitivity in Alzheimer's disease
Pomara N; Deptula D; Singh R
1989 ;317(1):1223-1233, Progress in clinical & biological research
In contrast to the well established presynaptic cholinergic deficits which are associated with Alzheimer's Disease (AD), the functional status of the remaining muscarinic receptors has not received adequate attention. This paper examined the possibility that the presynaptic cholinergic deficits in AD may be accompanied by muscarinic supersensitivity. While the majority of QNB binding studies have failed to find an upregulation of muscarinic receptors in AD patients, most of those studies did not differentiate between presynaptic and postsynaptic receptors. In addition, receptor density and functional response are not necessarily correlated. To determine whether AD is accompanied by alterations in the functional status of central muscarinic receptors, we studied the biological responses to a muscarinic agonist in AD patients and controls. In this pilot study, AD patients demonstrated an increased arecoline-induced HVA response in the CSF. This finding is consistent with the hypothesis that AD is accompanied by muscarinic supersensitivity
— id: 23700, year: 1989, vol: 317, page: 1223, stat: Journal Article,

CSF corticotropin-releasing factor (CRF) in Alzheimer's disease: its relationship to severity of dementia and monoamine metabolites
Pomara N; Singh RR; Deptula D; LeWitt PA; Bissette G; Stanley M; Nemeroff CB
1989 Sep;26(5):500-504, Biological psychiatry
The concentration of corticotropin-releasing factor-like immunoreactivity (CRF-LI) in the cerebrospinal fluid (CSF) of 15 probable Alzheimer's disease (AD) patients with mild to moderate dementia and 10 neurologically normal age-matched controls was examined. There were no significant alterations in the mean CSF CRF-LI concentration in AD compared to controls. However, in the AD group, CSF CRF-LI correlated significantly with the global neuropsychological impairment ratings, suggesting that greater cognitive impairment was associated with lower CSF CRF-LI concentrations. There was a significant reduction in the CSF concentration of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the AD patients, and there was a positive correlation between the concentration of CRF-LI and 5-HIAA in CSF. This latter finding suggests that serotoninergic neuronal systems may interact with CRF-containing neurons
— id: 23697, year: 1989, vol: 26, page: 500, stat: Journal Article,

The effects of diazepam and aging on intrusions
Pomara N; Deptula D; Rubinstein S; Stanley B; Stanley M
1988 ;24(2):228-231, Psychopharmacology bulletin
— id: 23702, year: 1988, vol: 24, page: 228, stat: Journal Article,

Loss of the cortisol response to naltrexone in Alzheimer's disease
Pomara N; Stanley M; Rhiew HB; Bagne CA; Deptula D; Galloway MP; Tanimoto K; Verebey K; Tamminga CA
1988 Apr 1;23(7):726-733, Biological psychiatry
The administration of a single dose of the opiate antagonist naltrexone (NT) was accompanied by significant elevations in plasma cortisol in normal elderly subjects; in contrast, the cortisol response to NT was absent in individuals of comparable age with Alzheimer's disease (AD). The differential effect of AD on the cortisol response was not accompanied by a significant group difference in plasma prolactin in response to NT administration. Furthermore, this differential cortisol response to NT was not associated with any evident differences in age, sex ratio, plasma levels of naltrexone or its major metabolite beta-naltrexol, or with differences in measures of nonspecific stress, such as plasma free MHPG, pulse, or blood pressure, between the two groups. The absence of the well-characterized cortisol response to NT in AD, together with other reports of abnormal responses to other pharmacological challenges, suggests that neuroendocrine abnormalities might be an important concomitant and possibly a central contributor to the pathophysiology of Alzheimer's disease
— id: 23701, year: 1988, vol: 23, page: 726, stat: Journal Article,

Comparison of methods for analysis of CSF proteins in patients with Alzheimer's disease
Townsend LE; Gilroy J; LeWitt P; Wolfe DE; Pomara N; Weintraub J; Reitz D
1987 Jun;6(3):213-229, Neurochemical pathology
Cerebrospinal fluid (CSF) from patients with Alzheimer's disease (AD) and controls was analyzed by one- and two-dimensional gel electrophoresis, electron microscopy, and fluorescence microscopy with thioflavin S staining. In CSF from patients with AD, abnormal proteins were found following two-dimensional gel electrophoresis and silver staining. In CSF samples from most of the AD patients studied, a highly argentophilic material was detected upon silver staining the stacking gel of the one-dimensional gels. Electron microscopy of material eluted from the stacking gel showed fibers of approximately 7-10 nm diameter, with some twisting; properties consistent with paired helical filaments or amyloid. Furthermore, material with the characteristics of amyloid (fiber diameter ranging from 4-10 nm) was found in the CSF sediment. The CSF from AD patients had significantly elevated numbers of yellow fluorescent particles following thioflavin S staining when compared with age-matched, other neurological disease controls. We did not see an increase in autofluorescence, indicating that thioflavin S staining is specific. Our data suggest that AD CSF contains plaque amyloid and possibly proteins from neurofibrillary tangles. The thioflavin S staining method appears to have potential for development as a diagnostic tool
— id: 23703, year: 1987, vol: 6, page: 213, stat: Journal Article,

Alzheimer's disease: Strategies for treatment and research
Bagne, Curtis A; Pomara, Nunzio; Crook, Thomas; Gershon, Samuel
Treatment development strategies for Alzheimer's disease Madison, CT, US: Mark Powley Associates, 1986,
(from the chapter) address both substantive issues of treatment and methodologic issues of science and clinical practice [in Alzheimer's disease (AD)] / suggests new treatment strategies as well as methods to improve the productivity of clinical research /// overview of treatment strategies [improve cerbral circulation, metabolic activation, neurotransmitter strategies, other treatment strategies, development of treatment rationales] / mechanisms of action--evolution of understanding / summary of clinical trials [vasodilators, hydergine, metabolic enhancers and nootropics, other treatments, additional reviews] / physostigmine / direct muscarinic agonists / naloxone and naltrexone / combination treatments / outcome assessment
— id: 4796, year: 1986, vol: , page: 585, stat: Chapter,

Electrophoresis and immunoblot of cerebrospinal fluid proteins in spasmodic torticollis
Cullis PA; Townsend L; LeWitt P; Pomara N; Reitz D
1986 ;1(3):179-186, Movement disorders
Protein patterns of cerebrospinal fluid (CSF) from patients with spasmodic torticollis (ST) were investigated to determine whether abnormalities previously reported could be detected and further identified. CSF was collected from 12 patients with ST and 6 normal controls. The CSF proteins were analyzed using sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis and silver staining. In 11 of the 12 patients with ST, a CSF protein pattern was observed which differed from that in the controls. The identity of the abnormal proteins was ascertained by blotting and immunostaining with specific antisera to IgG and ceruloplasmin (Cp). CSF from 2 of 12 patients had distinct bands staining for IgG and 7 had abnormal immunostaining for Cp
— id: 23706, year: 1986, vol: 1, page: 179, stat: Journal Article,

Prospective strategies for cholinergic interventions in Alzheimer's disease
Pomara N; Bagne CA; Stanley M; Yarbrough GG
1986 ;10(3-5):553-569, Progress in neuro-psychopharmacology & biological psychiatry
The cholinergic hypothesis of memory dysfunction has guided most of the recent proposals for treating the primary symptoms of AD. The efficacy of these treatments has been severely limited. This review examines two major lines of evidence which suggest that the cholinergic hypothesis may have to be expanded and revised. The cholinergic hypothesis focuses on pre-synaptic defects. It assumes cholinoceptive neurons would function normally with adequate stimulation. Evidence is not sufficient to support this assumption. In addition, dissociations have been demonstrated between muscarinic receptor number and functional response of cholinoceptive neurons. Various measures are proposed to investigate the functional integrity of muscarinic receptors in AD patients. AD often has been characterized as a disorder produced by generalized cholinergic hypoactivity. Evidence for cortisol hypersecretion, abnormal dexamethasone suppression, and the occurrence of depressive symptoms, motoric dysfunction and sleep abnormalities in AD patients is more consistent with regional cholinergic hyperactivity than generalized hypoactivity. Resolution of these discrepancies could shed new light on the pathophysiology and treatment strategies for AD. Cholinoceptive neurons could be hypersensitive, subsensitive or have unaltered responsivity. These options would have very different treatment implications. New developments in outcome assessment which are capable of discriminating varieties of differential response to treatment can spur treatment development and improve quality of care for patients with complex disorders such as AD
— id: 23705, year: 1986, vol: 10, page: 553, stat: Journal Article,

The cholinergic hypothesis of memory dysfunction in Alzheimer's disease--revisited
Pomara N; Stanley M
1986 ;22(1):110-118, Psychopharmacology bulletin
— id: 23704, year: 1986, vol: 22, page: 110, stat: Journal Article,

Clinical ratings: relationship to objective psychometric assessment in individuals with dementia
Block RI; DeVoe M; Russell M; Pomara N
1985 Aug;57(1):183-189, Psychological reports
— id: 23707, year: 1985, vol: 57, page: 183, stat: Journal Article,

Memory performance in individuals with primary degenerative dementia: its similarity to diazepam-induced impairments
Block RI; DeVoe M; Stanley B; Stanley M; Pomara N
1985 Autumn-Winter;11(3-4):151-155, Experimental aging research
Impairments of memory storage and retrieval produced by diazepam (2.5 mg, 5 mg, and 10 mg) in normal elderly individuals were compared to those observed in patients with primary degenerative dementia tested under nondrug conditions. The highest diazepam dose affected retrieval as well as storage processes in Buschke's 'selective reminding' task, producing impairments qualitatively similar to those shown by demented patients. All diazepam doses impaired Buschke task performance in the normal elderly individuals; normal young subjects, in contrast, showed no impairment with a low (2.5 mg) diazepam dose
— id: 23711, year: 1985, vol: 11, page: 151, stat: Journal Article,

Chelation therapy. Unproved modality in the treatment of Alzheimer-type dementia
Cardelli MB; Russell M; Bagne CA; Pomara N
1985 Aug;33(8):548-551, Journal of the American Geriatrics Society
Despite a dramatic increase in the understanding of the neuropathologic and neurochemical alterations accompanying Alzheimer's disease, by far the largest cause of progressive and incapacitating cognitive dysfunction in the elderly, physicians have as yet no pharmacologic agent that can be prescribed safely either to arrest or reverse this decline. This lack of effective therapeutic agents is contributing to the use by an increasing number of health professionals, including physicians and concerned families, of unproved, costly, and potentially dangerous modalities, such as chelation therapy. The purpose of this paper is to describe some individuals with Alzheimer-type dementia who have undergone chelation therapy
— id: 23708, year: 1985, vol: 33, page: 548, stat: Journal Article,

Event-related potential in Alzheimer disease
Chayasirisobhon S; Brinkman SD; Gerganoff S; Gershon S; Pomara N; Green V
1985 Jan;16(1):48-53, Clinical electroencephalography
Auditory event - related potentials were studied in 20 patients with SDAT and 20 age and sex matched normal controls. Patients with SDAT showed prolonged latencies of N200 and P300 components. The mean amplitudes of N200 and P300 were lower in the SDAT group. This reflects the impairment of the speed of neural processing in patients with SDAT. There were no significant correlations of the progression of P300 latencies from mild to severe dementia according to global dementia scales
— id: 23712, year: 1985, vol: 16, page: 48, stat: Journal Article,

Alterations in cholinergic receptors mediate the effects of dexamethasone on corticosterone
Gershon S; McIntyre IM; Pomara N; Stanley M; Oxenkrug G
1985 Apr;20(4):458-460, Biological psychiatry
— id: 23710, year: 1985, vol: 20, page: 458, stat: Journal Article,

Lithium neurotoxicity in patients with degenerative brain disease
Kelwala S; Pomara N; Stanley M
1985 ;46:354-354, Journal of clinical psychiatry
— id: 23738, year: 1985, vol: 46, page: 354, stat: Journal Article,

Multiple, single-dose naltrexone administrations fail to effect overall cognitive functioning and plasma cortisol in individuals with probable Alzheimer's disease
Pomara N; Roberts R; Rhiew HB; Stanley M; Gershon S
1985 Fall;6(3):233-236, Neurobiology of aging
A double-blind placebo-controlled study was conducted in 10 individuals with probable Alzheimer's disease to assess the effects of varying doses of Naltrexone (0, 25, 50 and 100 mg) on cognitive functioning and on plasma cortisol. Each individual participated in four separate sessions at least three days apart. Naltrexone was found to improve performance in only one of the six psychometric tasks employed (Token Test). However, enhancement of Token Test performance was limited to the 25 mg Naltrexone dose and was mainly the result of an improvement on the part of the two most severely impaired patients. In contrast to the previous reports of elevations of plasma cortisol following administration of opiate antagonists to younger, non-demented subjects, Naltrexone administration failed to produce any significant increase in plasma cortisol in Alzheimer's patients
— id: 23714, year: 1985, vol: 6, page: 233, stat: Journal Article,

Increased sensitivity of the elderly to the central depressant effects of diazepam
Pomara N; Stanley B; Block R; Berchou RC; Stanley M; Greenblatt DJ; Newton RE; Gershon S
1985 May;46(5):185-187, Journal of clinical psychiatry
The effects of diazepam on memory and psychomotor performance in healthy elderly (N = 12) and young (N = 12) individuals were examined. Diazepam was administered acutely in a single, oral 2.5 mg dose. Diazepam impaired memory, both immediate and delayed recall, and psychomotor performance in the elderly subjects. In addition, the drug caused an increase in self-reported sedation in elderly subjects but not in young subjects. These findings suggest an age-related increase in the sensitivity of elderly individuals to the central depressant effects of diazepam
— id: 23709, year: 1985, vol: 46, page: 185, stat: Journal Article,

The therapeutic potential of thyrotropin releasing hormone (TRH) in Alzheimer's disease (AD)
Yarbrough GG; Pomara N
1985 ;9(3):285-289, Progress in neuro-psychopharmacology & biological psychiatry
In recent years it has been established that patients with AD have a relatively specific loss of cerebral cortical and hippocampal cholinergic nerve terminals. This may be a reflection of degeneration of cholinergic neurons originating in the nucleus basalis of Meynert and septum which project to the cortex and hippocampus, respectively. In view of the long-standing association of cholinergic mechanisms with cognitive processes and the recognition of selective cholinergic deficits in AD, therapeutic attempts to enhance CNS cholinergic function have been undertaken in patients with AD. While only limited success with this strategy has been achieved to date, the use of TRH may offer a novel, yet rational, approach to treating AD. This assumption is predicated on the extensive literature documenting unique, facilitatory interactions of this peptide with cholinergic neurons throughout the neuraxis. Furthermore, the same rationale may account for the recently reported therapeutic benefit of TRH in patients with amyotrophic lateral sclerosis, which like AD, is a disease whose symptoms are manifested through a progressive degeneration of a subpopulation of CNS cholinergic neurons
— id: 23713, year: 1985, vol: 9, page: 285, stat: Journal Article,

Proline in the cerebrospinal fluid of normal subjects and Alzheimer's-disease patients, as determined with a new double-labeling assay technique
Baxter CF; Baldwin RA; Pomara N; Brinkman SD
1984 Oct;32(2):189-198, Biochemical medicine
Past studies have implicated proline involvement in the function of memory and learning. A new micromethod has been developed that is suitable for measuring proline accurately in as little as 0.1 ml of CSF. In normal human CSF, the average proline level was found to be consistently about 1.3 microM. In the CSF of patients with Alzheimer's disease and mixed dementias, the levels of proline showed no statistically significant difference from proline levels in the CSF of normal controls. Furthermore, the proline levels in the CSF of the Alzheimer's disease patients did not reflect, consistently, the cognitive deficits or the symptomatic severity of the disease. Proline levels in CSF showed no statistically significant change with the age of individuals tested
— id: 23716, year: 1984, vol: 32, page: 189, stat: Journal Article,

Prediction of serum cortisol response to dexamethasone in normal volunteers: a multivariate approach
Branconnier RJ; Oxenkrug GF; McIntyre I; Pomara N; Harto NE; Gershon S
1984 ;84(2):274-275, Psychopharmacology
Dexamethasone (DEX, 0.5 mg orally at 11 PM) challenge was used for the assessment of hypothalamic-pituitary-adrenal (HPA) activity in 20 normal volunteers. Age and pre-DEX serum cortisol levels were thee evaluated as predictors of postDEX serum cortisol levels using step-wise multiple regression analysis. Both age and preDEX serum cortisol levels were significant predictors of postDEX serum cortisol levels. It is suggested that the adjustment for age and preDEX serum cortisol level could be useful for the interpretation of abnormal postDEX levels
— id: 23725, year: 1984, vol: 84, page: 274, stat: Journal Article,

Lithium-induced increases in red blood cell choline and memory performance in Alzheimer-type dementia
Brinkman SD; Pomara N; Barnett N; Block R; Domino EF; Gershon S
1984 Feb;19(2):157-164, Biological psychiatry
To investigate the relationship between RBC choline and memory in Alzheimer-type senile dementia (SDAT), lithium carbonate was administered to 14 SDAT patients in doses of 400-600 mg/day for 5 weeks. A battery of memory tests was administered at baseline and at weekly intervals. Five patients with serum concentrations below 0.6 meq/liter developed neurotoxicity and were dropped from further analysis. For the remaining patients, Li+ with mean serum concentrations up to 0.6 meq/liter did not alter memory scores significantly. The dramatic increases in RBC choline during the study, however, suggest that RBC choline is not correlated with memory functioning in SDAT
— id: 23722, year: 1984, vol: 19, page: 157, stat: Journal Article,

Lithium-induced accentuation of extrapyramidal symptoms in individuals with Alzheimer's disease
Kelwala S; Pomara N; Stanley M; Sitaram N; Gershon S
1984 Aug;45(8):342-344, Journal of clinical psychiatry
Lithium treatment in 9 elderly individuals with Alzheimer's disease led to a marked accentuation of extra-pyramidal symptoms (EPS) in 5 of 6 patients with preexisting EPS. EPS scores significantly correlated with plasma and RBC lithium levels. Lithium treatment had no such effects in the 3 patients without preexisting extrapyramidal symptoms
— id: 23718, year: 1984, vol: 45, page: 342, stat: Journal Article,

Suicidal behavior: a neglected issue in DSM-III
Pomara N
1984 Jun;45(6):280-280, Journal of clinical psychiatry
— id: 23720, year: 1984, vol: 45, page: 280, stat: Journal Article,

Decay in plasma lithium and normalization in red blood cell choline following cessation of lithium treatment in two elderly individuals with Alzheimer-type dementia
Pomara N; Block R; Domino EF; Gershon S
1984 Jun;19(6):919-922, Biological psychiatry
— id: 23721, year: 1984, vol: 19, page: 919, stat: Journal Article,

Combined piracetam and cholinergic precursor treatment for primary degenerative dementia
Pomara N; Block R; Moore N; Rhiew HB; Berchou R; Stanley M; Gershon S
1984 ;12:388-389, IRCS journal of medical science
— id: 23737, year: 1984, vol: 12, page: 388, stat: Journal Article,

Myalgia and elevation in muscle creatine phosphokinase during zimelidine treatment
Pomara N; Coffman KL; Bush DF; Gershon S
1984 Aug;4(4):220-222, Journal of clinical psychopharmacology
The authors report a case involving a 65-year-old woman with DSM-III criteria for major unipolar depression in whom the administration of zimelidine, a potent and selective 5-hydroxytryptamine reuptake inhibitor, led to the development of a hypersensitivity reaction characterized by a severe headache, low grade fever, abnormal liver enzymes, and generalized myalgia 10 days after initiation of treatment. The most novel aspect of this hypersensitivity reaction to zimelidine was the development of abnormalities in muscle creatine phosphokinase in conjunction with the myalgia
— id: 23719, year: 1984, vol: 4, page: 220, stat: Journal Article,

Treatment-resistant depression in an elderly patient with pancreatic carcinoma: case report
Pomara N; Gershon S
1984 Oct;45(10):439-440, Journal of clinical psychiatry
A case is reported of a recurrent and treatment-resistant depression with a positive DST in an individual in whom adenocarcinoma of the pancreas was eventually diagnosed. Following excision of the tumor, there was increased therapeutic response to antidepressants and normalization of the DST
— id: 23717, year: 1984, vol: 45, page: 439, stat: Journal Article,

Does severity of dementia modulate response to dexamethasone in individuals with primary degenerative dementia?
Pomara N; Oxenkrug GF; McIntyre IM; Block R; Stanley M; Gershon S
1984 Oct;19(10):1481-1487, Biological psychiatry
— id: 23715, year: 1984, vol: 19, page: 1481, stat: Journal Article,

Adverse effects of single therapeutic doses of diazepam on performance in normal geriatric subjects: relationship to plasma concentrations
Pomara N; Stanley B; Block R; Guido J; Russ D; Berchou R; Stanley M; Greenblatt DJ; Newton RE; Gershon S
1984 ;84(3):342-346, Psychopharmacology
Elderly normal volunteers (N = 12, mean age 70.4 years) were administered placebo or diazepam 2.5, 5, 10 mg in four consecutive sessions separated by at least a 1-week interval. Memory and psychomotor performance and plasma diazepam concentrations were assessed at baseline and at 1 and 3 h following drug administration. Significant impairments were found in response to all doses of diazepam. The maximum impairment occurred at 1 h, which coincided with the highest plasma concentration of the drug
— id: 23724, year: 1984, vol: 84, page: 342, stat: Journal Article,

Diazepam impairs performance in normal elderly subjects
Pomara N; Stanley B; Block R; Guido J; Stanley M; Greenblatt DJ; Newton RE; Gershon S
1984 Winter;20(1):137-139, Psychopharmacology bulletin
— id: 23723, year: 1984, vol: 20, page: 137, stat: Journal Article,

Russell's revised Wechsler Memory Scale in the evaluation of dementia
Brinkman SD; Largen JW Jr; Gerganoff S; Pomara N
1983 Nov;39(6):989-993, Journal of clinical psychology
Matched 31 elderly normals and 25 patients with suspected Alzheimer's disease for age and education and administered the Revised Wechsler Memory Scale (WMS-R). The patient group performed significantly less well than the control group on all WMS-R subtests. A bimodal distribution of Percent Retained scores was noted in the patient group, but not in the control group. Results are discussed with respect to the clinical utility of the WMS-R as a memory screening procedure
— id: 23726, year: 1983, vol: 39, page: 989, stat: Journal Article,

Aging and cortisol resistance to suppression by dexamethasone: a positive correlation
Oxenkrug GF; Pomara N; McIntyre IM; Branconnier RJ; Stanley M; Gershon S
1983 Oct;10(2):125-130, Psychiatry research
Cortisol resistance to suppression by 0.5 mg of dexamethasone given at 11 p.m. was studied in 30 normal subjects, 17 to 78 years of age. Serum cortisol concentrations were determined by radioimmunoassay. A strong positive correlation was found between age and cortisol concentrations 9 hours after dexamethasone administration. The data suggest that aging, per se, might contribute to the increased cortisol resistance to suppression by dexamethasone reported in depression and dementia
— id: 23727, year: 1983, vol: 10, page: 125, stat: Journal Article,

Elevation of RBC glycine and choline levels in geriatric patients treated with lithium
Pomara N; Banay-Schwartz M; Block R; Stanley M; Gershon S
1983 Jul;140(7):911-913, American journal of psychiatry
During 6 weeks of lithium treatment, the RBC glycine and choline levels of five cognitively impaired geriatric subjects without affective disorders increased significantly and correlated with RBC and plasma lithium levels. The subjects' cognitive processes did not improve
— id: 23729, year: 1983, vol: 140, page: 911, stat: Journal Article,

Combined cholinergic precurson treatment and dihydroergotoxine mesylate in Alzheimer's disease
Pomara N; Block R; Abraham J; Domino EF; Gershon S
1983 ;11:1048-1049, IRCS journal of medical science
— id: 23736, year: 1983, vol: 11, page: 1048, stat: Journal Article,

Attenuation of pilocarpine-induced hypothermia in response to chronic administration of choline
Pomara N; Block R; Demetriou S; Fucek F; Stanley M; Gershon S
1983 ;80(2):129-130, Psychopharmacology
Chronic treatment of rats with choline caused a decrease in the hypothermic response to pilocarpine. The action of choline on the muscarinic receptors is consistent with electrophysiological and binding studies, supporting a direct muscarinic action for choline. Administration of direct muscarinic agonists has been shown to cause a decrease in the number of muscarinic receptors. Thus, the long-term use of cholinergic precursors could have some adverse effects on central cholinergic functioning
— id: 23730, year: 1983, vol: 80, page: 129, stat: Journal Article,

Caution in the use of diazepam in the elderly
Pomara N; Block R; Guido J; Stanley M
1983 ;308:1600-1601, New England journal of medicine
— id: 23739, year: 1983, vol: 308, page: 1600, stat: Journal Article,

Failure of single-dose lecithin to alter aspects of central cholinergic activity in Alzheimer's disease
Pomara N; Domino EF; Yoon H; Brinkman S; Tamminga CA; Gershon S
1983 Aug;44(8):293-295, Journal of clinical psychiatry
The effect of a single dose (15 g/70 kg) of lecithin (95% phosphatidylcholine) on several measures of central cholinergic activity (memory, cortisol, prolactin, pulse, blood pressure) was assessed in individuals with Alzheimer's disease. In contrast to the reported effects of physostigmine, a cholinesterase inhibitor, lecithin had no effect on these parameters, despite significant increases in plasma and erythrocyte choline
— id: 23728, year: 1983, vol: 44, page: 293, stat: Journal Article,

Lithium, memory RBC plasma choline in Alzheimer-type dementia
Brinkman SD; Pomara N; Domino EF; Barnett N; Gershon S
1982 ;10:326-327, IRCS journal of medical science
— id: 23735, year: 1982, vol: 10, page: 326, stat: Journal Article,

A dose-ranging study of lecithin in the treatment of primary degenerative dementia (Alzheimer disease)
Brinkman SD; Pomara N; Goodnick PJ; Barnett N; Domino EF
1982 Aug;2(4):281-285, Journal of clinical psychopharmacology
— id: 23732, year: 1982, vol: 2, page: 281, stat: Journal Article,

Cholinergic precursors in Alzheimer's disease
Pomara N; Stanley M
1982 Nov 6;2(8306):1049-1049, Lancet
— id: 23731, year: 1982, vol: 2, page: 1049, stat: Journal Article,

Psychopharmacotherapy: from the 1950s to the 1980s
Pomara N; Gershon S
1981 Jun;22(6):526-530, Psychosomatics
— id: 23733, year: 1981, vol: 22, page: 526, 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,

Increased pupillary miotic response to pilocarpine in cognitevely impaired elderly subjects
Sitaram N; Pomara N
1981 ;9:409-410, IRCS journal of medical science
— id: 23734, year: 1981, vol: 9, page: 409, stat: Journal Article,