Antonio Convit, M.D.

High cortisol levels are associated with low quality food choice in type 2 diabetes
Duong, Michelle; Cohen, Jessica I; Convit, Antonio
2012 Feb;41(1):76-81, Endocrine
Hypothalamic-pituitary-adrenal (HPA) axis control may be impaired in type 2 diabetes (T2DM). Glucocorticoids increase consumption of low quality foods high in calories, sugar, and fat. We explored the relationship between cortisol levels, poor blood glucose control, and food quality choice in T2DM. Twenty-seven healthy controls were age-, gender- and education-matched to 27 T2DM participants. Standard clinical blood tests and cortisol values were measured from fasting blood samples. Participants recorded all consumed food and drink items in a consecutive 3-day food diary. Diaries were analyzed for 'high quality' and 'low quality' foods using a standardized method with high reliability (0.97 and 0.86, respectively). Controlling for education, body mass index (BMI) and hemoglobin A1C (HbA1C), log-transformed cortisol (LogC) predicted the percent of low quality foods (R (2) = 0.092, beta = 0.360, P < 0.05), but not the percent of high quality foods chosen. Controlling for education, BMI, and LogC, HbA1C significantly predicted both the percent of low quality foods (DeltaR (2) = 0.079, beta = 0.348, P = 0.024) and high quality foods chosen (DeltaR (2) = 0.085, beta = -0.362, P = 0.022). The relationship between HbA1C and low quality food choice may be mediated by cortisol, controlling for BMI and education (P < 0.01). HbA1C displayed both an indirect (cortisol-mediated) effect (P < 0.05) and direct effect on low quality food choice (P < 0.05). The relationship between HbA1C and low quality food choice may be partially mediated by cortisol. Poor blood glucose control may cause HPA axis disruption, increased consumption of low quality foods
— id: 149794, year: 2012, vol: 41, page: 76, stat: Journal Article,

Type 2 diabetes affects hippocampus volume differentially in men and women
Hempel, R; Onopa, R; Convit, Antonio
2012 Jan;28(1):76-83, Diabetes/metabolism research & reviews
BACKGROUND: Type 2 diabetes mellitus (T2DM) has been shown to result in medical complications on several organ systems including the kidneys, eyes, cardiovascular system, and most recently described the brain, including the hippocampus. There is also evidence that females are disproportionately affected by these medical complications. Brain volume reductions have also been associated with chronic low-grade inflammation and dyslipidaemia. This study investigated the relationships among T2DM, gender, inflammation, dyslipidaemia, and hippocampal volumes. METHOD: Participant groups consisted of 40 obese adults with T2DM and 47 lean adults, group-matched on age, gender, race, and education. Each participant underwent medical examination including a standard panel of blood tests, a magnetic resonance imaging, and cognitive evaluation. RESULTS: We show that there is a gender difference in the association of T2DM and hippocampal volumes: diabetic women are most affected despite having better glucose control than their male counterparts. Although females with T2DM had disproportionately lower high density lipoprotein as well as better haemoglobin A1c, neither of these results explained why females with T2DM had the smallest hippocampal volumes. CONCLUSIONS: These important findings indicate that in addition to the higher rate of traditional medical complication, females with T2DM are likely to suffer more brain complications than males. These observations, if supported by larger studies, suggest that in the future gender could be considered when customizing diabetes treatment.
— id: 148723, year: 2012, vol: 28, page: 76, stat: Journal Article,

Systematic differences between lean and obese adolescents in brain spin-lattice relaxation time: a quantitative study
Cazettes, F; Tsui, W H; Johnson, G; Steen, R G; Convit, A
2011 Dec;32(11):2037-2042, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: Emerging evidence suggests that obese adolescents show changes in brain structure compared with lean adolescents. In addition, obesity impacts body development during adolescence. We tested a hypothesis that T1, a marker of brain maturation, can show brain differences associated with obesity. MATERIALS AND METHODS: Adolescents similar in sex, family income, and school grade were recruited by using strict entry criteria. We measured brain T1 in 48 obese and 31 lean adolescents by quantitative MR imaging at 1.5T. We combined MPRAGE and inversion-recovery sequences with normalization to standard space and automated skull stripping to obtain T1 maps with a symmetric voxel volume of 1 mm(3). RESULTS: Sex, income, triglycerides, total cholesterol, and fasting glucose did not differ between groups, but obese adolescents had significantly lower HDL, higher LDL, and higher fasting insulin levels than lean adolescents. Intracranial vault volume did not differ between groups, but obese adolescents had smaller intracranial vault-adjusted brain parenchymal volumes. Obese adolescents had 4 clusters (>100 contiguous voxels) of T1 relaxation that were significantly different (P < .005) from those in lean adolescents. Three of these clusters had longer T1s in obese adolescents (in the orbitofrontal and parietal regions), and 1 cluster had shorter T1s, compared with lean adolescents. CONCLUSIONS: Our results suggest that obesity may have a significant impact on brain development, especially in the frontal and parietal lobes. It is unclear if these changes persist into adulthood or whether they indicate that obese subjects follow a different developmental trajectory during adolescence
— id: 150559, year: 2011, vol: 32, page: 2037, stat: Journal Article,

Obesity-mediated inflammation may damage the brain circuit that regulates food intake
Cazettes, Fanny; Cohen, Jessica I; Yau, Po Lai; Talbot, Hugues; Convit, Antonio
2011 Feb 10;1373:101-109, Brain research
Adiposity is associated with chronic low-grade systemic inflammation and increased inflammation in the hypothalamus, a key structure in feeding behavior. It remains unknown whether inflammation impacts other brain structures that regulate feeding behavior. We studied 44 overweight/obese and 19 lean individuals with MRI and plasma fibrinogen levels (marker of inflammation). We performed MRI-based segmentations of the medial and lateral orbitofrontal cortex (OFC) and hippocampal volumes. Gray matter (GM) volumes were adjusted for head size variability. We conducted logistic and hierarchical regressions to assess the association between fibrinogen levels and brain volumetric data. Using diffusion tensor imaging (DTI), we created apparent diffusion coefficient (ADC) maps and conducted voxelwise correlational analyses. Fibrinogen concentrations were higher among the overweight/obese (t[61]=-2.33, P=0.023). Lateral OFC associated together with fibrinogen correctly classified those with excess of weight (accuracy=76.2%, sensitivity=95.5%, and specificity=31.6%). The lateral OFC volumes of overweight/obese were negatively associated with fibrinogen (r=-0.37, P=0.016) and after accounting for age, hypertension, waist/hip ratio and lipid and sugar levels, fibrinogen significantly explained an additional 9% of the variance in the lateral OFC volume (beta=-0.348, DeltaR(2)=0.093, DeltaF P=0.046). Among overweight/obese the associations between GM ADC and fibrinogen were significantly positive (P<0.001) in the left and right amygdala and the right parietal region. Among lean individuals these associations were negative and located in the left prefrontal, the right parietal and the left occipital lobes. This is the first study to report that adiposity-related inflammation may reduce the integrity of some of the brain structures involved in reward and feeding behaviors
— id: 121321, year: 2011, vol: 1373, page: 101, stat: Journal Article,

Obesity, orbitofrontal structure and function are associated with food choice: a cross-sectional study
Cohen, Jessica I; Yates, Kathy F; Duong, Michelle; Convit, Antonio
2011 Jan 1;1(2):e000175-e000175, BMJ Open
Objectives Obesity is on the rise in the US and is linked to the development of type 2 diabetes and cardiovascular disease. Emerging evidence over the last decade suggests that obesity may also adversely affect executive function and brain structure. Although a great deal of research focuses on how diet affects the brain and cognitive performance, no study focuses on how food choice may be associated with brain integrity. Here we investigated how lean and overweight/obese (o/o) adults differed in their food choices and how brain structure and cognition may be associated with those choices. Design As part of an ongoing study on diabetes and the brain, participants had routine blood work and a research MRI, received a battery of neurocognitive tests, and were instructed to keep a 3-day food diary. Results and conclusions The lean group ate more high quality foods and less low quality foods compared to the o/o group. In the o/o group, high quality food choices were associated with orbitofrontal cortex volume. The lean group performed better than the o/o group on neurocognitive measures of executive function, such as the Stroop Interference Test, the Wisconsin Card Sort Test and the Trail Making Test B-A, and on attention and concentration tasks such as the Digit Symbol Substitution Test. Taken together, these preliminary data suggest that in obesity poor food choices may be associated with frontal cognitive impairments that may be the result of, or contribute to, decreases in orbitofrontal cortex volume. Therefore, longitudinal studies are warranted to investigate a causal link between food choice and executive functioning
— id: 139748, year: 2011, vol: 1, page: e000175, stat: Journal Article,

Disinhibited eating in obese adolescents is associated with orbitofrontal volume reductions and executive dysfunction
Maayan, Lawrence; Hoogendoorn, Claire; Sweat, Victoria; Convit, Antonio
2011 Jul;19(7):1382-1387, Obesity (Silver Spring)
In adults, obesity has been associated with disinhibited eating, decreased cortical gray matter (GM) volume, and lower performance on cognitive assessments. Much less is known about these relationships in adolescence and there are no studies assessing behavioral, cognitive, and neurostructural measures in the same group of study participants. This study examined the relationship between obesity, executive function, disinhibition, and brain volumes in relatively healthy youth. Participants included 54 obese and 37 lean adolescents. Participants received a cognitive battery, questionnaires of eating behaviors, and magnetic resonance imaging (MRI). Neuropsychological assessments included tasks targeting frontal lobe function. Eating behaviors were determined using the Three Factor Eating Questionnaire (TFEQ), and structural MRIs were performed on a 1.5 T Siemens Avanto MRI System (Siemens, Erlangen, Germany) to determine brain GM volumes. Lean and obese adolescents were matched on age, years of education, gender, and socioeconomic status. Relative to lean adolescents, obese participants had significantly higher ratings of disinhibition on the TFEQ, lower performance on the cognitive tests, and lower orbitofrontal cortex (OFC) volume. Disinhibition significantly correlated with BMI, Stroop color-word score, and OFC volume. This is the first report of these associations in adolescents and point to the importance of better understanding the associations between neurostructural deficits and obesity
— id: 134717, year: 2011, vol: 19, page: 1382, stat: Journal Article,

"The application of the first order system transfer function for fitting The California Verbal Learning Test Learning Curve:" Corrigendum
Stepanov, Igor I; Abramson, Charles I; Wolf, Oliver T; Convit, Antonio
2011 ;17(1):206-, Journal of the International Neuropsychological Society
Reports an error in 'The application of the first order system transfer function for fitting The California Verbal Learning Test learning curve' by Igor I. Stepanov, Charles I. Abramson, Oliver T. Wolf and Antonio Convit (Journal of the International Neuropsychological Society, 2010[May], Vol 16[3], 443-452). In the original article, the version of the CVLT that was administered to the subject population was the CVLT-II. This is incorrect; the version administered was the CVLT. (The following abstract of the original article appeared in record 2010-10086-005). Very few attempts have been made to apply a mathematical model to the learning curve in the California Verbal Learning Test list A immediate recall. Our rationale was to find out whether modeling of the learning curve can add additional information to the standard CVLT-II measures. We applied a standard transfer function in the form Y = B3*exp(-B2*(X-l))+B4*(l-exp(-B2*(X-l))), where X is the trial number; Y is the number of recalled correct words, B2 is the learning rate, B3 is readiness to learn and B4 is ability to learn. The coefficients of the model were found to be independent measures not duplicating standard CVLT-II measures. Regression analysis revealed that readiness to learn (B3) and ability to learn (B4) were significantly (p < .05) higher in a group of healthy participants than in a group of participants with type 2 diabetes mellitus (T2DM), but the learning rate (B2) did not differ (p > .2). The proposed model is appropriate for clinical application and as a guide for research and may be used as a good supplemental tool for the CVLT-II and similar memory tests.
— id: 122280, year: 2011, vol: 17, page: 206, stat: Journal Article,

Neuroimaging supports central pathology in familial dysautonomia
Axelrod, Felicia B; Hilz, Max J; Berlin, Dena; Yau, Po Lai; Javier, David; Sweat, Victoria; Bruehl, Hannah; Convit, Antonio
2010 Feb;257(2):198-206, Journal of neurology
Familial dysautonomia (FD) is a hereditary peripheral and central nervous system disorder with poorly defined central neuropathology. This prospective pilot study aimed to determine if MRI would provide objective parameters of central neuropathology. There were 14 study subjects, seven FD individuals (18.6 +/- 4.2 years, 3 female) and seven controls (19.1 +/- 5.8 years, 3 female). All subjects had standardized brain MRI evaluation including quantitative regional volume measurements, diffusion tensor imaging (DTI) for assessment of white matter (WM) microstructural integrity by calculation of fractional anisotropy (FA), and proton MR spectroscopy ((1)H MRS) to assess neuronal health. The FD patients had significantly decreased FA in optic radiation (p = 0.009) and middle cerebellar peduncle (p = 0.004). Voxel-wise analysis identified both GM and WM microstructural damage among FD subjects as there were nine clusters of WM FA reductions and 16 clusters of GM apparent diffusion coefficient (ADC) elevations. Their WM proportion was significantly decreased (p = 0.003) as was the WM proportion in the frontal region (p = 0.007). (1)H MRS showed no significant abnormalities. The findings of WM abnormalities and decreased optic radiation and middle cerebellar peduncle FA in the FD study group, suggest compromised myelination and WM micro-structural integrity in FD brains. These neuroimaging results are consistent with clinical visual abnormalities and gait disturbance. Furthermore the frontal lobe atrophy is consistent with previously reported neuropsychological deficits
— id: 104788, year: 2010, vol: 257, page: 198, stat: Journal Article,

Cognitive impairment in nondiabetic middle-aged and older adults is associated with insulin resistance
Bruehl, H; Sweat, V; Hassenstab, J; Polyakov, V; Convit, A
2010 Jun;32(5):487-493, Journal of clinical & experimental neuropsychology
To determine whether the cognitive impairments observed in adults with type 2 diabetes mellitus (T2DM) exist in preclinical disease, we compared 38 adult participants with evidence of insulin resistance (IR) to 54 age-, gender-, and education-matched control participants on a battery of neuropsychological tests. We found that participants with IR had performance reductions in declarative memory and executive functioning. When we examined IR simultaneously with other biomedical indicators with which it co-occurs, only IR itself was associated with declarative memory, and hemoglobin A1c (HbA1c) was associated with executive functioning and working memory. We conclude that individuals with insulin resistance already demonstrate similar reductions in cognitive performance as those described in T2DM
— id: 110112, year: 2010, vol: 32, page: 487, stat: Journal Article,

The Role of the Fusiform-Amygdala System in the Pathophysiology of Autism
Dziobek, I; Bahnemann, M; Convit, A; Heekeren, HR
2010 APR ;67(4):397-405, Archives of general psychiatry
Context: Autism is a condition of unknown origin with well-documented impairments in social perception and cognition. Objective: To assess the relevance of the fusiform-amygdala system to the pathophysiology of autism spectrum conditions. Design: Cross-sectional case-control study. Setting: University hospital. Participants: A total of 27 adults with autism spectrum conditions and 29 age-, sex-, and intelligence quotient-matched typically developed healthy controls. Patients were assessed according to DSM-IV criteria using the Autism Diagnostic Interview-Revised. Interventions: We applied an automated measurement to estimate fusiform gyrus cortical thickness and a manual tracing method to obtain amygdala volumes. We analyzed volumetric covariance among these brain regions and assessed the functional relevance of anatomical findings by analyzing correlations with emotional face processing performance. Main Outcome Measures: Fusiform gyrus cortical thickness, amygdala volume, emotional face processing. Results: We found a specific local increase in cortical thickness of the fusiform gyrus and associated impairments in face processing in individuals with autism. Anatomical covariance between amygdala volume and the increase in fusiform gyrus local thickness was significantly smaller in the group with autism spectrum conditions. Conclusions: Our data provide the first anatomical evidence of an abnormal amygdala-fusiform system and its behavioral relevance to face-processing deficits in autism spectrum conditions. In light of recent evidence of the involvement of the fusiform gyrus and amygdala in social perception as well as the areas of social cognition and emotional awareness, all of which are relevant to autism, our findings might represent a core pathophysiological mechanism of autism
— id: 109074, year: 2010, vol: 67, page: 397, stat: Journal Article,

Metabolic syndrome is associated with learning and recall impairment in middle age
Hassenstab, Jason J; Sweat, Victoria; Bruehl, Hannah; Convit, Antonio
2010 ;29(4):356-362, Dementia geriatric & cognitive disorders
AIMS: To determine whether middle-aged individuals with metabolic syndrome, both with and without type 2 diabetes, exhibit cognitive impairments, and to determine the role of each metabolic syndrome component in those associations. METHODS: 143 participants were drawn from ongoing studies of normal aging. Metabolic syndrome was diagnosed in 73 participants (age: 60.4 +/- 8.4 years), who were contrasted with 70 age- and education-matched controls. RESULTS: Metabolic syndrome was associated with reductions in recall (p = 0.006), lower overall intellectual functioning (p = 0.013), and nearly significant reductions in learning (p = 0.066) and executive functioning (p = 0.050). These effects were only marginally attenuated when controlling for type 2 diabetes diagnosis. Of the 5 components of the metabolic syndrome, insulin resistance was the only significant predictor of variance in learning and recall. In addition, the number of metabolic syndrome criteria met was inversely associated with cognitive performance. CONCLUSIONS: These results indicate that impairments in cognitive functioning associated with metabolic syndrome and type 2 diabetes may begin as early as middle age and are primarily due to insulin resistance. These results demonstrate the importance of screening at-risk adults for insulin resistance in order to initiate lifestyle modifications to reverse or prevent these cognitive changes
— id: 109850, year: 2010, vol: 29, page: 356, stat: Journal Article,

The application of the first order system transfer function for fitting The California Verbal Learning Test Learning Curve
Stepanov, II; Abramson, CI; Wolf, OT; Convit, A
2010 MAY ;16(3):443-452, Journal of the International Neuropsychological Society
Very few attempts have been made to apply a mathematical model to the learning curve in the California Verbal Learning Test list A immediate recall. Our rationale was to find out whether modeling of the learning curve can add additional information to the standard CVLT-II measures. We applied a standard transfer function in the form Y = B3*exp(-B2*(X-1))+B4*(1-exp(-B2*(X-1))), where X is the trial number; Y is the number of recalled correct words, B2 is the learning rate, B3 is readiness to learn and B4 is ability to learn. The coefficients of the model were found to be independent measures not duplicating standard CVLT-II measures. Regression analysis revealed that readiness to learn (B3) and ability to learn (B4) were significantly (p < .05) higher in a group of healthy participants than in a group of participants with type 2 diabetes mellitus (T2DM), but the learning rate (B2) did not differ (p > .2). The proposed model is appropriate for clinical application and as a guide for research and may be used as a good supplemental tool for the CVLT-II and similar memory tests. (JINS, 2010, 16, 443-452.)
— id: 109772, year: 2010, vol: 16, page: 443, stat: Journal Article,

Preliminary evidence for brain complications in obese adolescents with type 2 diabetes mellitus
Yau, P L; Javier, D C; Ryan, C M; Tsui, W H; Ardekani, B A; Ten, S; Convit, A
2010 Nov;53(11):2298-2306, Diabetologia
AIMS/HYPOTHESIS: Central nervous system abnormalities, including cognitive and brain impairments, have been documented in adults with type 2 diabetes who also have multiple co-morbid disorders that could contribute to these observations. Assessing adolescents with type 2 diabetes will allow the evaluation of whether diabetes per se may adversely affect brain function and structure years before clinically significant vascular disease develops. METHODS: Eighteen obese adolescents with type 2 diabetes and 18 obese controls without evidence of marked insulin resistance, matched on age, sex, school grade, ethnicity, socioeconomic status, body mass index and waist circumference, completed MRI and neuropsychological evaluations. RESULTS: Adolescents with type 2 diabetes performed consistently worse in all cognitive domains assessed, with the difference reaching statistical significance for estimated intellectual functioning, verbal memory and psychomotor efficiency. There were statistical trends for executive function, reading and spelling. MRI-based automated brain structural analyses revealed both reduced white matter volume and enlarged cerebrospinal fluid space in the whole brain and the frontal lobe in particular, but there was no obvious grey matter volume reduction. In addition, assessments using diffusion tensor imaging revealed reduced white and grey matter microstructural integrity. CONCLUSIONS/INTERPRETATION: This is the first report documenting possible brain abnormalities among obese adolescents with type 2 diabetes relative to obese adolescent controls. These abnormalities are not likely to result from education or socioeconomic bias and may result from a combination of subtle vascular changes, glucose and lipid metabolism abnormalities and subtle differences in adiposity in the absence of clinically significant vascular disease. Future efforts are needed to elucidate the underlying pathophysiological mechanisms
— id: 113653, year: 2010, vol: 53, page: 2298, stat: Journal Article,

Plasma BDNF is reduced among middle-aged and elderly women with impaired insulin function: evidence of a compensatory mechanism
Arentoft, Alyssa; Sweat, Victoria; Starr, Vanessa; Oliver, Stephen; Hassenstab, Jason; Bruehl, Hannah; Tirsi, Aziz; Javier, Elizabeth; McHugh, Pauline F; Convit, Antonio
2009 Nov;71(2):147-152, Brain & cognition
Brain-derived neurotrophic factor (BDNF) plays a regulatory role in neuronal differentiation and synaptic plasticity and has been linked to glucose regulation and cognition. Associations among plasma BDNF, cognition, and insulin function were explored. Forty-one participants with impaired insulin function (IIF), ranging from insulin resistance to type 2 diabetes mellitus (T2DM), were matched with 41 healthy controls on gender, age, education, and IQ. Participants received complete medical, neurological, psychiatric, and neuropsychological evaluations. IIF individuals had significantly lower plasma BDNF levels than controls, particularly females, and higher BDNF levels were associated with poorer explicit memory in IIF females, suggesting that higher levels within this group may reflect the body's efforts to respond to damage. After accounting for age, education, and HbA1c, BDNF significantly predicted 13.1-23.5% of the variance in explicit memory in IIF women. These findings suggest that BDNF elevations within diseased groups may not always be a marker of health
— id: 101886, year: 2009, vol: 71, page: 147, stat: Journal Article,

A blunted cortisol awakening response and hippocampal atrophy in type 2 diabetes mellitus
Bruehl, Hannah; Wolf, Oliver T; Convit, Antonio
2009 Jul;34(6):815-821, Psychoneuroendocrinology
There is emerging evidence from healthy individuals, as well as direct and indirect evidence from psychiatric and neurological patients with disease-related hippocampal atrophy, linking the cortisol awakening response (CAR) to hippocampal volume. Type 2 diabetes mellitus (T2DM) is a metabolic disease that is also accompanied by hippocampal atrophy, and therefore can serve as a model for ascertaining the relationship between CAR and hippocampal volume. We contrasted a group of 18 individuals with T2DM with 12 matched controls on MRI-based hippocampal volume and salivary diurnal cortisol profile including CAR. Individuals with T2DM had smaller hippocampal volumes and exhibited a blunting of the CAR relative to controls, while diurnal cortisol was not affected. Across all subjects, fasting insulin and hippocampal volume were associated with the CAR, independent of diagnosis. Our findings support the hypothesis that hippocampal integrity is an important predictor of the CAR
— id: 99229, year: 2009, vol: 34, page: 815, stat: Journal Article,

Modifiers of cognitive function and brain structure in middle-aged and elderly individuals with type 2 diabetes mellitus
Bruehl, Hannah; Wolf, Oliver T; Sweat, Victoria; Tirsi, Aziz; Richardson, Stephen; Convit, Antonio
2009 Jul 14;1280:186-194, Brain research
Cognitive deficits and hippocampal atrophy, features that are shared with aging and dementia, have been described in type 2 diabetes mellitus (T2DM). T2DM is associated with obesity, hypertension, dyslipidemia, hypothalamic pituitary adrenocortical (HPA) axis abnormalities and inflammation, all of which have been shown to negatively impact the brain. However, since most reports in T2DM focused on glycemic control, the relative contribution of these modifying factors to the impairments observed in T2DM remains unclear. We contrasted 41 middle-aged dementia-free volunteers with T2DM (on average 7 years since diagnosis) with 47 age-, education-, and gender-matched non-insulin resistant controls on cognition and brain volumes. HPA axis activity and other modifiers that accompany T2DM were assessed to determine their impact on brain and cognition. Individuals with T2DM had specific verbal declarative memory deficits, reduced hippocampal and prefrontal volumes, and impaired HPA axis feedback control. Diminished cortisol suppression after dexamethasone and dyslipidemia were associated with decreased cognitive performance, whereas obesity was negatively related to hippocampal volume. Moreover, prefrontal volume was influenced by worse glycemic control. Thus, obesity and altered cortisol levels may contribute to the impact of T2DM on the hippocampal formation, resulting in decreased verbal declarative memory performance
— id: 100479, year: 2009, vol: 1280, page: 186, stat: Journal Article,

Retinal vessel abnormalities are associated with elevated fasting insulin levels and cerebral atrophy in nondiabetic individuals
Tirsi, Aziz; Bruehl, Hannah; Sweat, Victoria; Tsui, Wai; Reddy, Shantan; Javier, Elizabeth; Lee, Carol; Convit, Antonio
2009 Jun;116(6):1175-1181, Ophthalmology
OBJECTIVE: To determine the impact of insulin resistance short of diabetes on the arteriolar-to-venular ratio (AVR) and whether AVR is related to cerebral atrophy. DESIGN: Cross-sectional study. PARTICIPANTS: Forty-six nondiabetic subjects with normal glucose tolerance and varying degrees of insulin resistance ranging in age from 43 to 77 years. METHODS: Insulin resistance was assessed by fasting insulin and the homeostasis model assessment. Arteriolar-to-venular ratio was determined using digital retinal photography with a nonmydriatic camera, and retinal data were analyzed using a reliable semiautomated method. Cerebral atrophy was derived by means of manual tracing and thresholding procedures on structural magnetic resonance images. MAIN OUTCOME MEASURES: Arteriolar-to-venular ratio and cerebral atrophy. RESULTS: Hyperinsulinemia negatively impacted AVR. Furthermore, AVR was associated with cerebral atrophy. Both of these findings were independent of the effects of age and hypertension. CONCLUSIONS: These novel findings indicate that insulin resistance short of diabetes and independent of age and hypertension has a negative impact on retinal vessel health. Moreover, impaired retinal vessel health related to brain atrophy also was independent of hypertension and white matter hyperintensities. Given the connections between retinal and cerebral vasculature, this may offer a partial explanation for the presence of cognitive and brain abnormalities among individuals with insulin resistance. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article
— id: 99234, year: 2009, vol: 116, page: 1175, stat: Journal Article,

Emotional and neutral declarative memory impairments and associated white matter microstructural abnormalities in adults with type 2 diabetes
Yau, Po Lai; Javier, David; Tsui, Wai; Sweat, Victoria; Bruehl, Hannah; Borod, Joan C; Convit, Antonio
2009 Dec 30;174(3):223-230, Psychiatry research
Declarative memory impairment is frequently reported among adults with type 2 diabetes mellitus (T2DM), who also demonstrate hippocampal volume reduction. Our goals were to ascertain whether emotional memory, which is mediated by neural circuits overlapping those of declarative memory, is also affected. In addition we wanted to characterize cerebral white matter (WM) involvement in T2DM. We studied 24 middle-aged and elderly patients with T2DM who were free of obvious vascular pathology or a psychiatric disorder, and 17 age- and education-matched healthy individuals with no evidence of insulin resistance. We examined emotional and neutral memory and performed a whole-brain voxelwise WM assessment utilizing diffusion tensor imaging (DTI). We found clear evidence of impairment in declarative memory among diabetic subjects and in addition found some preliminary support to suggest a possible blunting of the memory facilitation by emotional material among female but not male diabetics. This report is also the first DTI assessment among individuals with T2DM, which after accounting for overt WM damage, revealed diffuse but predominantly frontal and temporal WM microstructural abnormalities, with extensive involvement of the temporal stem. Hierarchical regression analyses demonstrated that immediate, but not delayed, emotional memory performance was explained by temporal stem FA, independent of age, poor metabolic regulation, and systolic blood pressure. Given that the temporal lobe memory networks appear to be particularly vulnerable to the deleterious effects of T2DM, this may help explain the observed memory impairments among diabetics. Future efforts should better clarify, with a larger sample, whether emotional memory is affected in adults with T2DM and whether there are clear gender effects
— id: 105505, year: 2009, vol: 174, page: 223, stat: Journal Article,

Dissociation of cognitive and emotional empathy in adults with Asperger syndrome using the Multifaceted Empathy Test (MET)
Dziobek, Isabel; Rogers, Kimberley; Fleck, Stefan; Bahnemann, Markus; Heekeren, Hauke R; Wolf, Oliver T; Convit, Antonio
2008 Mar;38(3):464-473, Journal of autism & developmental disorders
Empathy is a multidimensional construct consisting of cognitive (inferring mental states) and emotional (empathic concern) components. Despite a paucity of research, individuals on the autism spectrum are generally believed to lack empathy. In the current study we used a new, photo-based measure, the Multifaceted Empathy Test (MET), to assess empathy multidimensionally in a group of 17 individuals with Asperger syndrome (AS) and 18 well-matched controls. Results suggested that while individuals with AS are impaired in cognitive empathy, they do not differ from controls in emotional empathy. Level of general emotional arousability and socially desirable answer tendencies did not differ between groups. Internal consistency of the MET's scales ranged from .71 to .92, and convergent and divergent validity were highly satisfactory
— id: 135328, year: 2008, vol: 38, page: 464, stat: Journal Article,

Hypothalamic-pituitary-adrenal axis dysregulation and memory impairments in type 2 diabetes
Bruehl, Hannah; Rueger, Melanie; Dziobek, Isabel; Sweat, Victoria; Tirsi, Aziz; Javier, Elizabeth; Arentoft, Alyssa; Wolf, Oliver T; Convit, Antonio
2007 Jul;92(7):2439-2445, Journal of clinical endocrinology & metabolism
CONTEXT: There is evidence of both hypothalamic-pituitary-adrenocortical (HPA) axis and cognitive dysfunction in type 2 diabetes mellitus (T2DM). However, the exact nature and the associations between these abnormalities remain unclear. OBJECTIVES: The aim of the study was to characterize the nature of the HPA dysregulation in T2DM and ascertain whether impaired cognition in T2DM could be attributed to these abnormalities. DESIGN: A cross-sectional study was performed, contrasting matched groups on HPA axis function and cognition by using the combined dexamethasone (DEX)/CRH test and a neuropsychological battery assessing declarative and working memory, attention, and executive function. SETTING: The study was conducted in a research clinic in an academic medical center. PARTICIPANTS: Participants were volunteers functioning in the cognitively normal range. We studied 30 middle-aged individuals with T2DM, on average 7.5 yr since diabetes diagnosis, and 30 age-, gender-, and education-matched controls. MAIN OUTCOME MEASURES: Basal cortisol levels, cortisol levels during the DEX/CRH test, and performance on neuropsychological tests were measured. RESULTS: Individuals with T2DM had elevated basal plasma cortisol levels, higher levels after DEX suppression, and a larger response to CRH (all P <or= 0.005). Among individuals with T2DM, cortisol levels during the DEX/CRH test were positively associated with glycosylated hemoglobin (P = 0.05), independent of age, body mass index, hypertension, and dyslipidemia. Diabetic subjects showed cognitive impairments restricted to declarative memory. Across all subjects, declarative memory was inversely associated with cortisol levels; however, these associations were subsumed by glycemic control (glycosylated hemoglobin). CONCLUSIONS: HPA hyperactivity and declarative memory deficits are present in T2DM. Both alterations may reflect the negative impact of poor glycemic control on the hippocampal formation
— id: 73699, year: 2007, vol: 92, page: 2439, stat: Journal Article,

Hypercholesterolemia in Asperger syndrome: independence from lifestyle, obsessive-compulsive behavior, and social anxiety
Dziobek, Isabel; Gold, Stefan M; Wolf, Oliver T; Convit, Antonio
2007 Jan 15;149(1-3):321-324, Psychiatry research
We report on elevated total cholesterol and low-density lipoprotein (LDL) levels in 22 individuals with Asperger syndrome compared with well-matched controls, after accounting for lifestyle variables and clinical symptomatology that could affect them. A potential role for dyslipidemia in the pathogenesis of some forms of autism is discussed
— id: 71413, year: 2007, vol: 149, page: 321, stat: Journal Article,

Hippocampal damage and memory impairments as possible early brain complications of type 2 diabetes
Gold, S M; Dziobek, I; Sweat, V; Tirsi, A; Rogers, K; Bruehl, H; Tsui, W; Richardson, S; Javier, E; Convit, A
2007 Apr;50(4):711-719, Diabetologia
AIMS/HYPOTHESIS: There is evidence that type 2 diabetes mellitus is associated with cognitive impairment. Most studies investigating this association have evaluated elderly individuals, after many years of diabetes, who generally have poor glycaemic control and significant vascular disease. The aim of the current study was to investigate the early cognitive consequences and associated brain correlates of type 2 diabetes. MATERIALS AND METHODS: With regard to cognition and brain measures, we compared 23 age-, sex- and education-matched control subjects with 23 mostly middle-aged individuals with relatively well-controlled diabetes of less than 10 years from the time of diagnosis. RESULTS: We found deficits in hippocampal-based memory performance and preservation of other cognitive domains. Relative to control subjects, individuals with diabetes had reductions in brain volumes that were restricted to the hippocampus. There was an inverse relationship between glycaemic control and hippocampal volume; in multivariate regression analysis, HbA(1c) was the only significant predictor of hippocampal volume, accounting for 33% of the observed variance. Other variables commonly associated with type 2 diabetes, such as elevated BMI, hypertension or dyslipidaemia, did not independently contribute to the variance in hippocampal volume. CONCLUSIONS/INTERPRETATION: These results suggest that the medial temporal lobe may be the first brain site affected by type 2 diabetes and that individuals in poorer metabolic control may be affected to a greater extent
— id: 74659, year: 2007, vol: 50, page: 711, stat: Journal Article,

Knowing what others know, feeling what others feel: A controlled study of empathy in psychotherapists
Hassenstab, Jason; Dziobek, Isabel; Rogers, Kimberley; Wolf, Oliver T; Convit, Antonio
2007 ;195(4):277-281 Apr, Journal of nervous & mental disease
There has been considerable interest in assessing whether psychotherapists have enhanced abilities in empathy and whether those abilities influence treatment outcomes. However, to date, studies have been hindered by inconsistent definitions of empathy and a reliance on assessment via self-report. The unique aim of this study was to ascertain the empathic abilities of psychotherapists using a multidimensional battery consisting of objective and self-report measures. We compared 19 therapists and 19 well-matched control subjects on several measures of empathy. On tests emphasizing the cognitive aspects of empathy, therapists were no different from controls when making inferences based on facial expressions but were significantly better when making inferences based on language. On a test emphasizing the emotional aspects of empathy, therapists did not report to be more empathically concerned than controls; however, on a test of emotion regulation, they reported less personal distress in response to the distress of others. In sum, therapists were better able to interpret the verbal cues of others and described themselves as more emotionally controlled in response to tense interpersonal situations. (journal abstract)
— id: 73053, year: 2007, vol: 195, page: 277, stat: Journal Article,

Who cares? Revisiting empathy in Asperger syndrome
Rogers, Kimberley; Dziobek, Isabel; Hassenstab, Jason; Wolf, Oliver T; Convit, Antonio
2007 Apr;37(4):709-715, Journal of autism & developmental disorders
A deficit in empathy has consistently been cited as a central characteristic of Asperger syndrome (AS), but previous research on adults has predominantly focused on cognitive empathy, effectively ignoring the role of affective empathy. We administered the Interpersonal Reactivity Index (IRI), a multi-dimensional measure of empathy, and the Strange Stories test to 21 adults with AS and 21 matched controls. Our data show that while the AS group scored lower on the measures of cognitive empathy and theory of mind, they were no different from controls on one affective empathy scale of the IRI (empathic concern), and scored higher than controls on the other (personal distress). Therefore, we propose that the issue of empathy in AS should be revisited.
— id: 72861, year: 2007, vol: 37, page: 709, stat: Journal Article,

Diabetes, sugar-coated but harmful to the brain
Starr, Vanessa L; Convit, Antonio
2007 Dec;7(6):638-642, Current opinion in pharmacology
Type 2 diabetes mellitus appears to directly impair cognition and brain function, independent of its associated cardiovascular disease. This is supported by the presence of similar findings among adults with insulin resistance (pre-diabetes) and obese children with type 2 diabetes, years before overt cardiovascular disease. Hippocampal based memory performance is impaired early in the disease, although deficits in executive function, attention, and psychomotor speed are also seen in more chronic disease and/or poorer disease control, particularly in the presence of co-morbidities such as hypertension. Although there has been some speculation as to possible links between diabetes and Alzheimer's Disease based on associations found in population studies, no convincing empirical evidence has been put forth and brain autopsy studies, the gold standard of Alzheimer's diagnosis, have not supported such a link. Future studies should focus on understanding the mechanisms for the cognitive impairments associated with type 2 diabetes. We propose that insulin resistance-associated impairments in vascular reactivity and endothelial function are possible candidates as they may impact substrate delivery across the blood-brain-barrier. These are important issues given the obesity epidemic and the associated rising prevalence of insulin resistance and type 2 diabetes
— id: 75672, year: 2007, vol: 7, page: 638, stat: Journal Article,

Introducing MASC: a movie for the assessment of social cognition
Dziobek, Isabel; Fleck, Stefan; Kalbe, Elke; Rogers, Kimberley; Hassenstab, Jason; Brand, Matthias; Kessler, Josef; Woike, Jan K; Wolf, Oliver T; Convit, Antonio
2006 Jul;36(5):623-636, Journal of autism & developmental disorders
In the present study we introduce a sensitive video-based test for the evaluation of subtle mindreading difficulties: the Movie for the Assessment of Social Cognition (MASC). This new mindreading tool involves watching a short film and answering questions referring to the actors' mental states. A group of adults with Asperger syndrome (n = 19) and well-matched control subjects (n = 20) were administered the MASC and three other mindreading tools as part of a broader neuropsychological testing session. Compared to control subjects, Asperger individuals exhibited marked and selective difficulties in social cognition. A Receiver Operating Characteristic (ROC) analysis for the mindreading tests identified the MASC as discriminating the diagnostic groups most accurately. Issues pertaining to the multidimensionality of the social cognition construct are discussed
— id: 68763, year: 2006, vol: 36, page: 623, stat: Journal Article,

The 'amygdala theory of autism' revisited: linking structure to behavior
Dziobek, Isabel; Fleck, Stefan; Rogers, Kimberley; Wolf, Oliver T; Convit, Antonio
2006 ;44(10):1891-1899, Neuropsychologia
The 'amygdala theory of autism' suggests a crucial role for the amygdala in the neurobiological basis of autism spectrum disorders. However, to date evidence is lacking of a direct relationship between amygdala measures and behavioral manifestations of autism in affected individuals. In 17 adult individuals with Asperger syndrome (AS) and 17 well-matched controls we therefore assessed associations between MRI-derived amygdala volume and behavioral variables of emotion recognition and social cognition, as well as with core AS symptomatology. Results revealed that individuals with AS exhibited impairments in emotion recognition and social cognition compared to controls and also showed atypical relationships between amygdala volumes and overall head size. We found positive associations between emotional and social understanding and amygdala volume in the control group, but not in the AS group. In the AS group however, amygdala size was negatively related to diagnostic parameters, with smaller amygdala volumes involving higher levels of restricted-repetitive behavior domains. Our data seem to indicate that in AS the amygdala is not crucially involved in social and emotional understanding. It may, however, be a mediator for narrow interest patterns and the imposition of routines and rituals. Our data, in conjunction with current literature, seem to argue for a modification of the 'amygdala theory of autism'
— id: 68657, year: 2006, vol: 44, page: 1891, stat: Journal Article,

Links between cognitive impairment in insulin resistance: An explanatory model
Convit, Antonio
2005 Dec;26 Suppl 1:31-35, Neurobiology of aging
Cognitive function and peripheral glucose regulation both decrease with age. There is a consistent and growing literature reporting memory and other cognitive problems among individuals with diabetes mellitus as well as those with pre-diabetes. There are two papers in the literature documenting, relative to matched controls, hippocampal volume reductions among both diabetics and insulin resistant individuals. The mechanism(s) for the cognitive and brain problems associated with impairments in peripheral glucose regulation remain unknown. In this paper, I present a selective review of the literature that builds a case for a theoretical model that could be used to investigate how abnormalities in peripheral glucose regulation may give rise to brain impairments in general, and affect hippocampal integrity in particular
— id: 60254, year: 2005, vol: 26 Suppl 1, page: 31, stat: Journal Article,

The role of quantitative structural imaging in the early diagnosis of Alzheimer's disease
Glodzik-Sobanska, Lidia; Rusinek, Henry; Mosconi, Lisa; Li, Yi; Zhan, Jiong; de Santi, Susan; Convit, Antonio; Rich, Kenneth; Brys, Miroslaw; de Leon, Mony J
2005 Nov;15(4):803-26, x, Neuroimaging clinics of North America
The goal of this article is to review the role of structural neuroimaging in the diagnosis of Alzheimer's disease (AD). We present relevant neuroanatomy, highlight progress in the domain of AD imaging, and review the clinical characteristics of the prodromal phase of AD. We describe the history of the diagnostic issue by examining at cross-section and longitudinally the differences between patients who have AD and normal controls. We also present how subsequent works applied these characteristic traits to the early detection of the prodromal disease and to prediction of future decline. The article delineates the differences between subjects who have mild cognitive impairment and AD, which illustrate the spreading of the pathology with disease progression. The last section describes problems encountered in the differential diagnosis
— id: 64158, year: 2005, vol: 15, page: 803, stat: Journal Article,

Reduced hippocampal metabolism in MCI and AD: automated FDG-PET image analysis
Mosconi, L; Tsui, W-H; De Santi, S; Li, J; Rusinek, H; Convit, A; Li, Y; Boppana, Madhu; de Leon, M J
2005 Jun 14;64(11):1860-1867, Neurology
BACKGROUND: To facilitate image analysis, most recent 2-[18F]fluoro-2-deoxy-d-glucose PET (FDG-PET) studies of glucose metabolism (MRglc) have used automated voxel-based analysis (VBA) procedures but paradoxically none reports hippocampus MRglc reductions in mild cognitive impairment (MCI) or Alzheimer disease (AD). Only a few studies, those using regions of interest (ROIs), report hippocampal reductions. The authors created an automated and anatomically valid mask technique to sample the hippocampus on PET (HipMask). METHODS: Hippocampal ROIs drawn on the MRI of 48 subjects (20 healthy elderly [NL], 16 MCI, and 12 AD) were used to develop the HipMask. The HipMask technique was applied in an FDG-PET study of NL (n = 11), MCI (n = 13), and AD (n = 12), and compared to both MRI-guided ROIs and VBA methods. RESULTS: HipMask and ROI hippocampal sampling produced significant and equivalent MRglc reductions for contrasts between MCI and AD relative to NL. The VBA showed typical cortical effects but failed to show hippocampal MRglc reductions in either clinical group. Hippocampal MRglc was the only discriminator of NL vs MCI (78% accuracy) and added to the cortical MRglc in classifying NL vs AD and MCI vs AD. CONCLUSIONS: The new HipMask technique provides accurate and rapid assessment of the hippocampus on PET without the use of regions of interest. Hippocampal glucose metabolism reductions are found in both mild cognitive impairment and Alzheimer disease and contribute to their diagnostic classification. These results suggest re-examination of prior voxel-based analysis 2-[18F]fluoro-2-deoxy-d-glucose PET studies that failed to report hippocampal effects
— id: 61248, year: 2005, vol: 64, page: 1860, stat: Journal Article,

Subjective memory complaints in aging are associated with elevated cortisol levels
Wolf, Oliver T; Dziobek, Isabel; McHugh, Pauline; Sweat, Victoria; de Leon, Mony J; Javier, Elizabeth; Convit, Antonio
2005 Nov-Dec;26(10):1357-1363, Neurobiology of aging
The origin and clinical significance of subjective memory complaints among middle aged and older individuals is not well understood. Associations with objective memory impairments, personality traits or mood disturbances have been reported. Elevated cortisol levels occur in aging and depression and causal links to cognitive or emotional problems have been suggested. The goal of this study was to investigate the associations between basal and feedback indices of cortisol regulation and subjective memory impairment in a sample of healthy middle aged and older subjects (mean age 61.8 years) with (n=27) and without (n=19) subjective memory complaints. Participants with memory complaints had both higher basal cortisol levels and higher cortisol levels after dexamethasone. There was a significant group by gender interaction for basal cortisol levels, where women without memory complaints showed significantly lower cortisol levels, whereas no such difference was found for the men. All effects were not due to slight differences in depression scores. Differences in personality traits or in stress susceptibility might underlie the present findings. Future studies of memory complaints should take a comprehensive approach including relevant endocrine parameters
— id: 71969, year: 2005, vol: 26, page: 1357, stat: Journal Article,

Longitudinal neuroimaging measures of hippocampal formation atrophy and biomarkers for early Alzheimer disease
de Leon, MJ; DeSanti, S; Segal, S; Convit, A; Rusinek, H; Saint Louis, LA; Li, Y; Li, J; Mehta, PD; Zinkowski, R; Pratico, D; DeBernardis, J; Kerkman, D; Hampel, H; Clark, C
2004 APR ;25(12):S7-S7, Neurobiology of aging
— id: 42444, year: 2004, vol: 25, page: S7, stat: Journal Article,

Reduced glucose tolerance is associated with poor memory performance and hippocampal atrophy among normal elderly
Convit, Antonio; Wolf, Oliver T; Tarshish, Chaim; de Leon, Mony J
2003 Feb 18;100(4):2019-2022, Proceedings of the National Academy of Sciences of the United States of America
Poor glucose tolerance and memory deficits, short of dementia, often accompanies aging. The purpose of this study was to ascertain whether, among nondiabetic, nondemented middle-aged and elderly individuals, poorer glucose tolerance is associated with reductions in memory performance and smaller hippocampal volumes. We studied 30 subjects who were evaluated consecutively in an outpatient research setting. The composition of the participant group was 57% female and 68.6 +/- 7.5 years of age; the participants had an average education of 16.2 +/- 2.3 years, a score on the Mini Mental State Examination of 28.6 +/- 1.5, a glycosylated hemoglobin (HbA1C) of 5.88 +/- 0.74%, and a body mass index of 24.9 +/- 4.1 kg/m(2). Glucose tolerance was measured by an i.v. glucose tolerance test. Memory was tested by using the Wechsler Paragraphs recall tests at the time of administering the i.v. glucose tolerance test. The hippocampus and other brain volumes were measured by using validated methods on standardized MRIs. Decreased peripheral glucose regulation was associated with decreased general cognitive performance, memory impairments, and atrophy of the hippocampus, a brain area that is key for learning and memory. These associations were independent of age and Mini Mental State Examination scores. Therefore, these data suggest that metabolic substrate delivery may influence hippocampal structure and function. This observation may bring to light a mechanism for aging brain injury that may have substantial medical impact, given the large number of elderly individuals with impaired glucose metabolism
— id: 39314, year: 2003, vol: 100, page: 2019, stat: Journal Article,

Regional brain atrophy rate predicts future cognitive decline: 6-year longitudinal MR imaging study of normal aging
Rusinek, Henry; De Santi, Susan; Frid, Dina; Tsui, Wai-Hon; Tarshish, Chaim Y; Convit, Antonio; de Leon, Mony J
2003 Dec;229(3):691-696, Radiology
PURPOSE: To determine if medial temporal lobe (MTL) atrophy rate, assessed by using an automated procedure over the initial time interval of a 6-year, three-time-point longitudinal study, is predictive of future memory decline. MATERIALS AND METHODS: Healthy elderly subjects (age, >60 years) were administered a comprehensive battery of neuropsychometric tests and underwent magnetic resonance (MR) imaging at baseline and two or more follow-up examinations. The rate of brain atrophy between the baseline and first follow-up examinations was assessed by using an automated procedure that included spatial coregistration of the two images and regional brain boundary shift analysis. At final observation, the 45 subjects were separated into a group of those who did and a group of those who did not show objective evidence of cognitive decline. A forward stepwise logistic regression model was used to identify variables that predicted decline. RESULTS: Thirty-two subjects remained healthy, and 13 showed cognitive decline. Among subjects who showed cognitive decline, six declined after the second observation. MTL atrophy rate, through its interactions with sex and age, was the most significant predictor of decline. The overall accuracy of prediction was 89% (in 40 of 45 subjects), with 91% specificity (in 29 of 32 subjects) and 85% sensitivity (in 11 of 13 subjects). CONCLUSION: Among healthy elderly individuals, increased MTL atrophy rate appears to be predictive of future memory decline
— id: 43857, year: 2003, vol: 229, page: 691, stat: Journal Article,

Longitudinal cerebrospinal fluid tau load increases in mild cognitive impairment
de Leon, M J; Segal, S; Tarshish, C Y; DeSanti, S; Zinkowski, R; Mehta, P D; Convit, A; Caraos, C; Rusinek, H; Tsui, W; Saint Louis, L A; DeBernardis, J; Kerkman, D; Qadri, F; Gary, A; Lesbre, P; Wisniewski, T; Poirier, J; Davies, P
2002 Nov 29;333(3):183-186, Neuroscience letters
Cross-sectional cerebrospinal fluid (CSF) levels of tau and amyloid (A) beta (beta) are of diagnostic importance for Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, most longitudinal studies of tau fail to demonstrate progression. Because predominantly brain-derived proteins such as tau, have higher ventricle to lumbar ratios, we hypothesized that adjusting for the ventricular enlargement of AD would correct for the dilution of tau, and improve detection of longitudinal change. Abeta which is not exclusively brain derived, shows a ratio <1, and no benefit was expected from adjustment. In a 1 year longitudinal study of eight MCI and ten controls, we examined CSF levels of hyperphosphorylated (P) tau231, Abeta40, and Abeta42. In cross-section, MCI patients showed elevated Ptau231 and Abeta40 levels, and greater ventricular volumes. Longitudinally, only after adjusting for the ventricular volume and only for Ptau231, were increases seen in MCI. Further studies are warranted on mechanisms of tau clearance and on using imaging to interpret CSF studies
— id: 39372, year: 2002, vol: 333, page: 183, stat: Journal Article,

Basal hypothalamo-pituitary-adrenal axis activity and corticotropin feedback in young and older men: relationships to magnetic resonance imaging-derived hippocampus and cingulate gyrus volumes
Wolf, Oliver T; Convit, Antonio; de Leon, Mony J; Caraos, Conrado; Qadri, Syed F
2002 Apr;75(4):241-249, Neuroendocrinology
Alterations in basal cortisol secretion and feedback sensitivity are reported in aging. However, it is not known whether these hypothalamus-pituitary-adrenal (HPA) axis alterations are related to structural brain changes. This study was designed to investigate these relationships in the human. Nine young (24.0 +/- 1.2 years; mean +/- SE; range: 19-30) and 11 older (69.0 +/- 1.8 years; range: 59-76) men, in addition to having standardized magnetic resonance imaging of their brains, were given 0.5 mg/kg cortisol or placebo intravenously in a double-blind, crossover study. As expected, older men had significantly smaller volumes for all brain regions. Although the groups did not differ in baseline HPA axis activity, there were significant and specific relationships between the brain volumes and the baseline measures of HPA activity. Namely, for young and older subjects combined and after controlling for age and cerebral vault size, hippocampal volumes were inversely associated with 24-hour urinary cortisol and basal corticotropin (ACTH) levels, and the anterior cingulate gyrus volume was negatively correlated with baseline ACTH. Elderly subjects had a slower decrease in ACTH levels (percent of baseline level) during the first 30 min after cortisol administration. However, no associations were observed between the ACTH feedback indices and any brain measure. This report, although based on a small number of subjects, supports previous studies showing a blunted ACTH fast feedback during normal aging. Hippocampal atrophy appears to be related to increased basal measures of HPA axis activity, but not to fast ACTH feedback. It remains possible that age-associated changes in fast feedback may be related to changes to other brain sites, such as hypothalamus or pituitary
— id: 39663, year: 2002, vol: 75, page: 241, stat: Journal Article,

Salivary cortisol day profiles in elderly with mild cognitive impairment
Wolf, Oliver T; Convit, Antonio; Thorn, Elissa; de Leon, Mony J
2002 Oct;27(7):777-789, Psychoneuroendocrinology
It is unknown whether hypothalamus-pituitary-adrenal (HPA) axis dysfunction is associated with the memory impairments observed among elderly participants with mild cognitive impairment (MCI), a group considered at increased risk for Alzheimer's disease (AD). Therefore, salivary cortisol levels were measured at six points over the course of the day while at-home in MCI participants (n=16), normal elderly (n=28), and young controls (n=14). Results revealed that MCI participants did not show elevated salivary cortisol levels. The 9 a.m. cortisol level of the MCI group was significantly lower than the 9 a.m. level of the young controls, but did not differ from those of the normal elderly group. In contrast to the other two groups, within the MCI group mean cortisol levels were inversely related to immediate recall of paragraphs. No association was observed between mean cortisol levels and performance in paired associates and digit span. Whether cortisol levels, in conjunction with other factors, such as hippocampal volume, will lead to improved prediction of future decline to AD in participants with MCI remains to be established in longitudinal studies
— id: 39606, year: 2002, vol: 27, page: 777, stat: Journal Article,

Volumetric analysis of the pre-frontal regions: findings in aging and schizophrenia
Convit A; Wolf OT; de Leon MJ; Patalinjug M; Kandil E; Caraos C; Scherer A; Saint Louis LA; Cancro R
2001 Aug 25;107(2):61-73, Psychiatry research
Frontal lobe dysfunction is thought to be involved in schizophrenia and age-associated cognitive decline. Frontal lobe volume changes have been investigated in these conditions using MRI, but results have been inconsistent. Few volumetric MRI protocols exist that divide the pre-frontal cortex into its sub-regions. In the present article, we describe a new method, which allows assessment of the superior, middle and inferior frontal gyrus, as well as the orbitofrontal and cingulate regions. The method uses multiple planes to help guide the anatomical decisions and combines this with a geometric approach utilizing readily apparent anatomical landmarks. Using this protocol, the frontal lobe volumes in young healthy subjects were contrasted with those of young schizophrenic patients and elderly healthy subjects (nine male subjects per group). The results showed that the method could be reproduced with high reliability (r(icc)> or =0.88-0.99). Schizophrenic as well as old subjects had specific significant reductions in the superior frontal gyrus and orbitofrontal regions compared with the young group. However, old and schizophrenic subjects did not differ from each another. No volume differences were observed in the other three regions assessed. Whether or not these volume reductions reflect a common pathological process remains to be investigated in future studies
— id: 26623, year: 2001, vol: 107, page: 61, stat: Journal Article,

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

Hippocampal formation glucose metabolism and volume losses in MCI and AD
De Santi S; de Leon MJ; Rusinek H; Convit A; Tarshish CY; Roche A; Tsui WH; Kandil E; Boppana M; Daisley K; Wang GJ; Schlyer D; Fowler J
2001 Jul-Aug;22(4):529-539, Neurobiology of aging
We used MRI volume sampling with coregistered and atrophy corrected FDG-PET scans to test three hypotheses: 1) hippocampal formation measures are superior to temporal neocortical measures in the discrimination of normal (NL) and mild cognitive impairment (MCI); 2) neocortical measures are most useful in the separation of Alzheimer disease (AD) from NL or MCI; 3) measures of PET glucose metabolism (MRglu) have greater diagnostic sensitivity than MRI volume. Three groups of age, education, and gender matched NL, MCI, and AD subjects were studied. The results supported the hypotheses: 1) entorhinal cortex MRglu and hippocampal volume were most accurate in classifying NL and MCI; 2) both imaging modalities identified the temporal neocortex as best separating MCI and AD, whereas widespread changes accurately classified NL and AD; 3) In most between group comparisons regional MRglu measures were diagnostically superior to volume measures. These cross-sectional data show that in MCI hippocampal formation changes exist without significant neocortical changes. Neocortical changes best characterize AD. In both MCI and AD, metabolism reductions exceed volume losses
— id: 21136, year: 2001, vol: 22, page: 529, stat: Journal Article,

The histological validation of post mortem magnetic resonance imaging-determined hippocampal volume in Alzheimer's disease
Bobinski M; de Leon MJ; Wegiel J; Desanti S; Convit A; Saint Louis LA; Rusinek H; Wisniewski HM
2000 ;95(3):721-725, Neuroscience
For 11 AD cases and four normal elderly controls, post mortem volumes of the hippocampal subdivisions were calculated by using magnetic resonance imaging and histological sections. After at least six weeks of fixation in formalin, brains were examined on a 1.5-T Philips Gyroscan imager producing T1-weighted coronal images with a 3-mm slice thickness. Brains were then processed and embedded in paraffin. Serial coronal sections, 3 mm apart and stained with Cresyl Violet, were used for the planimetry and unbiased estimation of the total numbers of neurons in the hippocampal subdivisions. For all 15 cases, magnetic resonance imaging- and histology-based measurements were performed along the whole rostrocaudal extent of the hippocampal formation and included three subvolumes: (i) the hippocampus (CA1-CA4 and the dentate gyrus); (ii) hippocampus/subiculum; and (iii) hippocampus/parahippocampal gyrus. After controlling for shrinkage, strong correlations were found between magnetic resonance imaging and histological measurements for the hippocampus (r = 0.97, P < 0.001), hippocampus/subiculum (r = 0.95, P < 0.001) and hippocampus/parahippocampal gyrus (r = 0.89, P < 0.001). We also calculated the total number of neurons in the hippocampus and hippocampus/subiculum subvolumes. Strong correlations between the magnetic resonance imaging subvolumes and neuronal counts were found for the hippocampus (r = 0.90, P < 0.001) and the hippocampus/subiculum subvolume (r = 0.84, P < 0.001). We conclude that very accurate volumetric measurements of the whole hippocampal formation can be obtained by using a magnetic resonance imaging protocol. Moreover, the strong correlations between magnetic resonance imaging-based hippocampal volumes and neuronal numbers suggest the anatomical validity of magnetic resonance imaging volume measurements
— id: 8584, year: 2000, vol: 95, page: 721, stat: Journal Article,

Atrophy of the medial occipitotemporal, inferior, and middle temporal gyri in non-demented elderly predict decline to Alzheimer's disease
Convit A; de Asis J; de Leon MJ; Tarshish CY; De Santi S; Rusinek H
2000 Jan-Feb;21(1):19-26, Neurobiology of aging
Our goal was to ascertain, among normal elderly and individuals with mild cognitive impairment, which temporal lobe neocortical regions predicted decline to dementia of the Alzheimer's type (DAT). Individuals received an MRI at baseline and a clinical and cognitive evaluation at baseline and follow-up. By using the baseline MRI we assessed the anatomical subdivisions of the temporal lobe: anteromedial temporal lobe (hippocampus and parahippocampal gyrus), medial occipitotemporal (fusiform) gyrus, middle and inferior temporal gyri, and superior temporal gyrus. We studied two groups of carefully screened age- and education-matched elderly individuals: 26 normal elderly (NL) and 20 individuals with mild cognitive impairment (MCI). Fourteen individuals (12 from the MCI group and two from the NL group) declined to DAT within the 3.2-year follow-up interval. We used logistic regression analyses to ascertain whether the baseline brain volumes were useful predictors of decline to DAT at follow-up after accounting for age, gender, individual differences in brain size, and other variables known to predict DAT. After accounting for age, gender, and head size, adding the volume of the anteromedial temporal lobe (the aggregate of hippocampus and parahippocampal gyrus) and an index of global atrophy raised the accuracy of overall classification to 80.4%. However, the ability to detect those individuals who declined (sensitivity) was low at 57%. When baseline medial occipitotemporal and the combined middle and inferior temporal gyri were added to the logistic model, the overall classification accuracy reached 95.6% and, most importantly, the sensitivity rose to 92.8%. These data indicate that the medial occipitotemporal and the combined middle and inferior temporal gyri may be the first temporal lobe neocortical sites affected in AD; atrophy in these areas may herald the presence of future AD among nondemented individuals. No other clinical baseline variables examined predicted decline with sensitivities above 71%. The apolipoprotein APOE epsilon4 genotype was not associated with decline
— id: 9442, year: 2000, vol: 21, page: 19, stat: Journal Article,

Neuropsychology and neuroimaging of alcohol and illicit drug abuse
Bates ME; Convit A
Assessment of neuropsychological functions in psychiatric disorders Washington DC : American Psychiatric Press, 1999,
— id: 4004, year: 1999, vol: , page: ?, stat: Chapter,

MRI of entorhinal cortex in mild Alzheimer's disease
Bobinski M; de Leon MJ; Convit A; De Santi S; Wegiel J; Tarshish CY; Saint Louis LA; Wisniewski HM
1999 Jan 2;353(9146):38-40, Lancet
— id: 9443, year: 1999, vol: 353, page: 38, stat: Journal Article,

MRI volume of the amygdala: a reliable method allowing separation from the hippocampal formation
Convit A; McHugh P; Wolf OT; de Leon MJ; Bobinski M; De Santi S; Roche A; Tsui W
1999 Apr 26;90(2):113-123, Psychiatry research
Studies of MRI-derived volume of the amygdala have been mostly performed on coronal sections where its boundaries with the hippocampus and the entorhinal cortex are indistinct. To date, all reports of in vivo amygdala volume have consistently overestimated the size of the structure. We have developed a method for the MRI-based in vivo measurement of the amygdala volume which allows a better separation of the amygdala from the adjoining hippocampal formation. In nine normal volunteers we obtained three-dimensional spoiled gradient recalled acquisition, 1.3-mm thick, T1 weighted sagittal MR images and created electronically linked reformatted images in the coronal and axial planes. On the original sagittal and the reformatted axial planes, where it is more readily apparent, we delineated the boundaries between the amygdala and the hippocampus and the amygdala and the hippocampo-amygdala transition area, respectively. We then projected those markings onto the coronal plane, where the other boundaries of the amygdala are more easily seen. Using these markings as a guide and utilizing extra-amygdalar coronal landmarks for the anterior end, we outlined the whole amygdala on the coronal plane and determined its volume. We observed that 45% of the coronal slices that contained amygdala also contained some hippocampus. The amygdala measurement had high test-retest reliability, with an intra-class correlation coefficient (rICC) of 0.99 for the total volume and an rICC of 0.93 for the measurement at the level of the individual slice. The average amygdala volume was 1.05 +/- 0.17 cm3 on the right and 1.14 +/- 0.15 cm3 on the left. Our amygdala volumes are in agreement with those reported in postmortem studies, which provides the reported method with face validity
— id: 6200, year: 1999, vol: 90, page: 113, stat: Journal Article,

Effects of cortisol on memory and attention in healthy young and old men
Wolf, OT; Convit, A; Singh, A; Kandil, E; de, Santi S; Tarshish, CY; Gruen, RJ; McEwen, BS; de Leon, MJ
1999 Oct 23-28;25(1-2):896-896, Abstracts (Society for Neuroscience)
— id: 15852, year: 1999, vol: 25, page: 896, stat: Journal Article,

Cortisol levels during human aging predict hippocampal atrophy and memory deficits [see comments] [published erratum appears in Nat Neurosci 1998 Aug;1(4):329]
Lupien SJ; de Leon M; de Santi S; Convit A; Tarshish C; Nair NP; Thakur M; McEwen BS; Hauger RL; Meaney MJ
1998 May;1(1):69-73, Nature neuroscience
Elevated glucocorticoid levels produce hippocampal dysfunction and correlate with individual deficits in spatial learning in aged rats. Previously we related persistent cortisol increases to memory impairments in elderly humans studied over five years. Here we demonstrate that aged humans with significant prolonged cortisol elevations showed reduced hippocampal volume and deficits in hippocampus-dependent memory tasks compared to normal-cortisol controls. Moreover, the degree of hippocampal atrophy correlated strongly with both the degree of cortisol elevation over time and current basal cortisol levels. Therefore, basal cortisol elevation may cause hippocampal damage and impair hippocampus-dependent learning and memory in humans
— id: 7666, year: 1998, vol: 1, page: 69, stat: Journal Article,

Hippocampal volumes in cognitively normal persons at genetic risk for Alzheimer's disease
Reiman EM; Uecker A; Caselli RJ; Lewis S; Bandy D; de Leon MJ; De Santi S; Convit A; Osborne D; Weaver A; Thibodeau SN
1998 Aug;44(2):288-291, Annals of neurology
Brain imaging techniques have the potential to characterize neurobiological changes that precede the onset of cognitive impairment in persons at risk for Alzheimer's disease. As previously described, positron emission tomography (PET) was used to compare 11 cognitively normal persons 50 to 62 years of age who were homozygous for the epsilon4 allele of apolipoprotein E and 22 persons without the epsilon4 allele with a reported family history of Alzheimer's dementia who were matched for sex, age, and level of education. The epsilon4 homozygotes had significantly reduced glucose metabolism in the same brain regions as patients with Alzheimer's dementia; the largest reduction was in the posterior cingulate cortex. As described here, magnetic resonance imaging (MRI) was used to compare hippocampal volumes in the same subject groups. The epsilon4 homozygotes showed nonsignificant trends for smaller left and right hippocampal volumes; overall, smaller hippocampal volumes were associated with reduced performance on a long-term memory test. Whereas PET measurements of cerebral glucose metabolism begin to decrease before the onset of memory decline, MRI measurements of hippocampal volume begin to decrease in conjunction with memory decline in cognitively normal persons at risk for Alzheimer's disease
— id: 7752, year: 1998, vol: 44, page: 288, stat: Journal Article,

Specific hippocampal volume reductions in individuals at risk for Alzheimer's disease
Convit A; De Leon MJ; Tarshish C; De Santi S; Tsui W; Rusinek H; George A
1997 Mar-Apr;18(2):131-138, Neurobiology of aging
Our goal was to ascertain the involvement of the temporal lobe in the preclinical (not yet diagnosable) stages of dementia of the Alzheimer's type (DAT) by using MRI-derived volumes. We assessed anatomical subdivisions of the temporal lobe on three groups of carefully screened age- and education-matched elderly individuals: 27 normal elderly (NL), 22 individuals with minimal cognitive impairment (MCI), who did not fulfill DAT criteria but were regarded at high risk for future DAT, and 27 DAT individuals. We found hippocampal volume reductions of 14% for the MCI and 22% for the DAT group compared to the NL group. Utilizing regression analyses and after accounting for gender head size-age, generalized atrophy (CSF), and other temporal lobe subvolumes, the hippocampal volume separated NL from MCI individuals, correctly classifying 74%. For NL and MCI groups combined the hippocampal volume was the only temporal lobe subvolume related to delayed recall memory performance. When contrasting MCI and DAT individuals, the fusiform gyrus volume uniquely improved the ability of the hippocampal volume to separate MCI from DAT individuals from 74 to 80%. Our cross-sectional data suggest that, within the temporal lobe, specific hippocampal volume reductions separated the group at risk for DAT from the normal group. By the time impairments are sufficient to allow a diagnosis of DAT to be made, in addition to the medial temporal lobe volume reductions, the lateral temporal lobe is also showing volume reductions, most saliently involving the fusiform gyrus
— id: 7134, year: 1997, vol: 18, page: 131, stat: Journal Article,

Hippocampal atrophy as detected by width of the temporal horn is greater in Alzheimer dementia than in nondementing cognitive impairment - Comment
Convit, A; deLeon, MJ; Tarshish, C; DeSanti, S; Wells, C; George, A; SaintLouis, LA; Rusinek, H
1997 JUN-JUL ;18(6):1193-1195, AJNR. American journal of neuroradiology
— id: 73272, year: 1997, vol: 18, page: 1193, stat: Journal Article,

Contribution of structural neuroimaging to the early diagnosis of Alzheimer's disease
de Leon MJ; Convit A; DeSanti S; Bobinski M; George AE; Wisniewski HM; Rusinek H; Carroll R; Saint Louis LA
1997 ;9 Suppl 1:183-190, International psychogeriatrics
There is compelling evidence for the early involvement of the hippocampal formation in the natural history of Alzheimer's disease (AD). The evidence comes from recent neuropathology, neuropsychology, and neuroimaging studies. AD-type histopathologic changes limited to the hippocampus have been described and may be seen in normal aging subjects. The sites of maximal neuronal loss in the hippocampal formation are in the CA1, subiculum, and entorhinal cortex. Minimally cognitively impaired (MCI) individuals (defined by ratings of functional capacity and psychiatric symptomatology) exhibit a neuropsychological profile that is distinct from that of the unimpaired elderly. Pathologic evidence suggests that most of these cases already have AD brain changes accentuated in the hippocampal region, and our own longitudinal studies reveal that 70% of this group develop dementia within a 4-year period. We have developed a negative-angle axial view designed to cut parallel to the anterior-posterior plane of the hippocampus. Using this modified axial plane of section in conjunction with computed tomography (CT) and magnetic resonance imaging (MRI), we estimated the prevalence of hippocampal atrophy in normal aging and across severity levels of cognitively impaired elderly patients. Longitudinal study shows that hippocampal atrophy is a sensitive and specific predictor of future AD for patients with MCI. MRI volume study of AD patients, controls, and MCI patients shows specific hippocampal volume loss in MCI. We conclude that the atrophic changes associated with early AD can be visualized using qualitative techniques and are readily quantifiable with volumetry. This article is not intended to be comprehensive, but to provide an overview of some of the structural neuroimaging data from our laboratory
— id: 9444, year: 1997, vol: 9 Suppl 1, page: 183, stat: Journal Article,

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

Cortisol reduces hippocampal glucose metabolism in normal elderly, but not in Alzheimer's disease
de Leon MJ; McRae T; Rusinek H; Convit A; De Santi S; Tarshish C; Golomb J; Volkow N; Daisley K; Orentreich N; McEwen B
1997 Oct;82(10):3251-3259, Journal of clinical endocrinology & metabolism
Glucocorticoids are known to play a role in the regulation of peripheral glucose mobilization and metabolism. Although several animal studies have shown that hippocampal glucose metabolism is reduced acutely and chronically by the action of corticosterone and that excess glucocorticoids are harmful to hippocampal neurons, little is known about the central effects of glucocorticoids in the human. In this study we examined the brain glucose utilization (CMRglu) response to hydrocortisone (cortisol) in seven normal elderly and eight Alzheimer's disease (AD) patients. On 2 separate days, immediately after the administration of a bolus of either 35 mg hydrocortisone or placebo, we administered 2-deoxy-2-[18F]fluoro-D-glucose. After a 35-min radiotracer uptake period, positron emission tomography (PET) images were collected. PET CMRglu images were analyzed using two methods: an image transformation that allowed analyses across cases on a voxel by voxel basis, and an anatomically based region of interest method that used coregistered magnetic resonance imaging scans. Both image analysis methods yielded similar results, identifying relative to placebo, a specific hippocampal CMRglu reduction in response to the hydrocortisone challenge that was restricted to the normal group. The region of interest technique showed CMRglu reductions of 16% and 12% in the right and left hippocampi, respectively. Blood collected during the PET scans showed, for the normal group, a rise in plasma glucose levels, starting approximately 25 min after hydrocortisone administration. The AD group did not show this effect. Baseline cortisol was elevated in the AD group, but the clearance of hydrocortisone was not different between the groups. In conclusion, these data show that among normal individuals in the presence of a pharmacological dose of cortisol, the glucose utilization of the hippocampus is specifically reduced, and serum glucose levels increase. Based in part on other studies, we offer the interpretation that glucocorticoid-mediated regulation of glucose transport is altered in AD, and this may underlie both the hippocampal insensitivity to cortisol and the failure in these patients to mount a peripheral glucose response. As our findings could reflect an altered state of the AD patients, we interpret our results as preliminary with respect to evidence for metabolic abnormalities in AD. The results suggest the continued study of the hydrocortisone challenge as a test of hippocampal responsivity
— id: 9447, year: 1997, vol: 82, page: 3251, stat: Journal Article,

Imaging the brain in dementia: expensive and futile?
George AE; de Leon MJ; Golomb J; Kluger A; Convit A
1997 Nov-Dec;18(10):1847-1850, AJNR. American journal of neuroradiology
— id: 9445, year: 1997, vol: 18, page: 1847, stat: Journal Article,

Frontotemporal abnormalities and violent behavior
Convit, Antonio; Douyon, Richard; Yates, Kathy F.; Smith, Gwenn
Aggression and violence: Genetic, neurobiological, and biosocial perspectives Mahwah, N.J. : Lawrence Erlbaum, 1996,
(from the chapter) presents a simple conceptual framework based on the construct that frontotemporal abnormality is related to violent behavior / attempt to link this abnormality with more general constructs such as poor impulse control / review the literatures on aspects of brain function, drawing specifically from the literature that links frontotemporal dysfunction and violence among psychiatric and criminal populations / briefly make some linkages to the literature on poor impulse control (impulsivity) and its neurochemical substrate / impulsivity, its possible serotonin substrate, and its relationship to violence is the focus present 2 pilot studies [of violent schizophrenic male inpatients], which together with some of [the authors'] prior work, support the contention that there may be a relationship between frontotemporal dysfunction and violence among schizophrenic inpatients / propose a theoretical framework for future research that expands on the concept of frontotemporal brain dysfunction, and propose specific tools for the implementation of such a framework / [Ss for the pilot studies were 26.2-39.4 yrs]
— id: 2467, year: 1996, vol: , page: 169, stat: Chapter,

In vivo structural studies of the hippocampus in normal aging and in incipient Alzheimer's disease
de Leon MJ; Convit A; George AE; Golomb J; de Santi S; Tarshish C; Rusinek H; Bobinski M; Ince C; Miller D; Wisniewski H
1996 Jan 17;777:1-13, Annals of the New York Academy of Sciences
Population trends indicate that in the near future the size of the elderly population will increase. This will result in a large increment in the numbers of persons suffering mild to severe levels of cognitive impairment. While considerable efforts continue to be made to explain brain changes associated with Alzheimer disease (AD), little is known of the brain changes in aging without dementia or so-called normal aging. Pathologic studies suggest that the medial temporal lobe is informative in the examination of the early brain changes related to AD. However, pathologic studies only offer a single observation and considerable uncertainty exists regarding the likelihood of progression of disease and the development of dementia. Several structural neuroimaging studies have recently investigated this anatomy and recent reports are encouraging for a medial temporal lobe based diagnosis for age-related cognitive impairments. We will present our findings on the MRI anatomy of the hippocampal formation as well as data bearing on the use of hippocampal formation imaging in the diagnosis of AD and as a predictive marker for future dementia. Our findings suggest an anatomically specific relationship between hippocampal volume and secondary memory performance. Because these observations apply to nondemented and normal elderly subjects, we are encouraged that the anatomy of age-related cognitive impairments can be reliably recognized and possibly put to use in therapeutic studies
— id: 6989, year: 1996, vol: 777, page: 1, stat: Journal Article,

Age-related changes in brain: I. Magnetic resonance imaging measures of temporal lobe volumes in normal subjects
Convit A; de Leon MJ; Hoptman MJ; Tarshish C; De Santi S; Rusinek H
1995 Winter;66(4):343-355, Psychiatric quarterly
The volume of temporal lobe structures was examined in twenty-seven older (mean age of 69.2 +/- 8.3 years) and ten younger subjects (mean age of 26.1 +/- 4.1 years) using quantitative magnetic resonance imaging (MRI) methods. Multiple regression analysis, using gender, overall atrophy, and head size as covariates, showed unique contributions of age to variance in both medial and lateral temporal lobe volumes. Temporal lobe subregions that showed the strongest unique age-related reductions were the hippocampus, fusiform gyrus, and parahippocampus. These results suggest age-related reductions in temporal lobe subvolumes
— id: 9455, year: 1995, vol: 66, page: 343, stat: Journal Article,

Hippocampal volume losses in minimally impaired elderly
Convit A; de Leon MJ; Tarshish C; De Santi S; Kluger A; Rusinek H; George AE
1995 Jan 28;345(8944):266-266, Lancet
— id: 9453, year: 1995, vol: 345, page: 266, stat: Journal Article,

HIPPOCAMPAL ATROPHY AND COGNITIVE IMPAIRMENT - REPLY
CONVIT, A; DELEON, MJ; TARSHISH, C; DESANTI, S; RUSINEK, H; GEORGE, AE
1995 APR 15 ;345(8955):992-992, Lancet
— id: 73276, year: 1995, vol: 345, page: 992, stat: Journal Article,

The hippocampus in aging and Alzheimer's disease
de Leon MJ; Convit A; DeSanti S; Golomb J; Tarshish C; Rusinek H; Bobinski M; Ince C; Miller DC; Wisniewski HM
1995 Feb;5(1):1-17, Neuroimaging clinics of North America
The role of imaging in the evaluation of neurodegenerative disorders is summarized. The primary role of imaging is to exclude potentially treatable disorders such as meningioma, extracerebral hematoma, Wernicke's disease, and hypothyroidism. Atrophic changes dominate in the hippocampal region on Alzheimer's disease versus the anterior, frontal, and temporal lobes in Pick's disease. Signal hypointensity in the putamen on T2-weighted spin-echo images favors poorly drug-responsive Parkinson's disease whereas putaminal hyperintensity is observed with Creutzfeldt-Jacob, Wilson's, and Leigh's diseases. As our population ages, a thorough understanding of imaging findings in a geriatric population assumes an increasing importance
— id: 6602, year: 1995, vol: 5, page: 1, stat: Journal Article,

Age-related changes in brain: II. Positron emission tomography of frontal and temporal lobe glucose metabolism in normal subjects
De Santi S; de Leon MJ; Convit A; Tarshish C; Rusinek H; Tsui WH; Sinaiko E; Wang GJ; Bartlet E; Volkow N
1995 Winter;66(4):357-370, Psychiatric quarterly
While many neuropsychological studies have demonstrated age-related performance alterations in tests thought to reflect frontal and temporal lobe function, there is little direct observation and comparison of these hypothesized brain changes in vivo. The cerebral glucose metabolism of frontal, temporal, and cerebellar regions was examined in 40 young (mean = 27.5 +/- 4.9) and 31 elderly (mean = 67.6 +/- 8.8) normal males using PET-FDG. Univariate analysis showed age-related metabolic reductions in all frontal and temporal lobe regions. The reductions ranged from 13%-24% with the greatest changes in the frontal lobes. Multiple regression analyses showed a stronger age relationship with frontal lobe than with temporal lobe metabolism. The dorsal lateral frontal lobe was the region that appears to change most within the frontal lobes. Examination of the temporal lobe showed that age contributed equally to the metabolic variance of both the lateral temporal lobe and hippocampus. These results suggest that age-related metabolic changes exist in both frontal and temporal lobes and that the frontal lobe change is greater
— id: 9454, year: 1995, vol: 66, page: 357, stat: Journal Article,

Serotonin in violent patients with schizophrenia
Kunz M; Sikora J; Krakowski M; Convit A; Cooper TB; Volavka J
1995 Nov 29;59(1-2):161-163, Psychiatry research
CSF levels of 5-hydroxyindolacetic acid (5-HIAA), the serotonin metabolite, were assayed in 10 violent and 10 matched nonviolent patients with schizophrenia. Mean group levels of 5-HIAA in cerebrospinal fluid were found to be nearly identical. Possible explanations, including effects of medications, are discussed
— id: 60301, year: 1995, vol: 59, page: 161, stat: Journal Article,

Effect of subtle neurological dysfunction on response to haloperidol treatment in schizophrenia
Convit A; Volavka J; Czobor P; de Asis J; Evangelista C
1994 Jan;151(1):49-56, American journal of psychiatry
OBJECTIVE: The primary purpose of this study was to assess whether an interaction between subtle neurological impairment and haloperidol plasma level affects treatment response and, if so, the impact on negative symptoms in particular. METHOD: Forty-three schizophrenic and two schizoaffective inpatients diagnosed according to Research Diagnostic Criteria were given, at the end of a 1-week placebo period, a baseline evaluation consisting of the Brief Psychiatric Rating Scale (BPRS), Scales for the Assessment of Positive and Negative Symptoms, Quantified Neurological Scale, and the Simpson-Angus Scale for extrapyramidal side effects. Subjects were randomly assigned to one of three haloperidol plasma ranges and treated for 6 weeks. At the end point the BPRS, Scales for the Assessment of Positive and Negative Symptoms, and Simpson-Angus Scale were readministered. Multiple linear regressions were used to assess the extent to which the interaction between neurological abnormality and haloperidol plasma level predicted the end-point symptoms once the baseline symptoms, neurological abnormality, and haloperidol plasma level were accounted for. RESULTS: Those patients with higher levels of overall abnormality on the Quantified Neurological Scale at baseline and with frontal dysfunction in particular, had, with increasing haloperidol plasma levels, more severe negative symptoms at end point. Neurological dysfunction was not related to end-point positive symptoms. The effect was specific to end-point negative symptoms and was independent of extrapyramidal side effects. CONCLUSIONS: If confirmed, these findings may indicate that relatively intact frontal function is needed for improvement in negative symptoms and that those patients with schizophrenia who have subtle neurological dysfunction should be treated with lower doses of neuroleptics
— id: 61035, year: 1994, vol: 151, page: 49, stat: Journal Article,

Hippocampal atrophy correlates with severe cognitive impairment in elderly patients with suspected normal pressure hydrocephalus
Golomb J; de Leon MJ; George AE; Kluger A; Convit A; Rusinek H; de Santi S; Litt A; Foo SH; Ferris SH
1994 May;57(5):590-593, Journal of neurology neurosurgery & psychiatry
Measurements of hippocampal formation atrophy using MRI have been useful in distinguishing demented patients with a diagnosis of probable Alzheimer's disease from cognitively normal controls. To determine whether there is a similar relationship between hippocampal size and dementia in elderly patients suspected of normal pressure hydrocephalus (NPH), the authors obtained mini-mental status examination (MMSE) scores and MRI measurements of hippocampal size and CSF volume on 16 elderly patients whose severe ventriculomegaly and unexplained gait impairment made NPH a probable diagnosis. Hippocampal size correlated strongly with MMSE score (r = 0.75, p < 0.001); no significant MMSE correlation was found for ventricular CSF volume or extra-ventricular/ventricular CSF ratio. It was concluded that hippocampal atrophy is associated with severe cognitive dysfunction in many elderly patients with a diagnosis of NPH. As a hypothesis for further investigation, the detection of such atrophy may help identify cases where the presence of a pathology of Alzheimer's disease complicates the diagnosis of NPH
— id: 6390, year: 1994, vol: 57, page: 590, stat: Journal Article,

Hippocampal formation size in normal human aging: a correlate of delayed secondary memory performance
Golomb J; Kluger A; de Leon MJ; Ferris SH; Convit A; Mittelman MS; Cohen J; Rusinek H; De Santi S; George AE
1994 May-Jun;1(1):45-54, Learning & memory
Although mild progressive memory impairment is commonly associated with normal human aging, it is unclear whether this phenomenon can be explained by specific structural brain changes. In a research sample of 54 medically healthy and cognitively normal elderly persons (ages 55-87, x = 69.0 +/- 7.9), magnetic resonance imaging (MRI) was used to derive head-size-adjusted measurements of the hippocampal formation (HF) (dentate gyrus, hippocampus proper, alveus, fimbria, subiculum), the superior temporal gyrus (STG), and the subarachnoid cerebrospinal fluid (CSF) (to estimate generalized cerebral atrophy). Subjects were administered tests of primary memory (digit span) and tests of secondary memory with immediate and delayed recall components (paragraph, paired associate, list recall; facial recognition). Separate composite scores for the immediate and delayed components were created by combining, with equal weighting, the subtests of each category. The WAIS vocabulary subtest was used as a control measure for language and intelligence. A highly significant correlation (P < 0.001), independent of age, gender, and generalized cerebral atrophy was found between HF size and delayed memory performance. No significant correlations were found between HF size and primary or immediate memory performance. STG size was not significantly correlated with any of the composite memory variables. These results suggest that HF atrophy may play an important independent role in contributing to the memory loss experienced by many aging adults
— id: 6632, year: 1994, vol: 1, page: 45, stat: Journal Article,

INVOLUNTARY MEDICATION OF PATIENTS WHO ARE INCOMPETENT TO STAND TRIAL - A REVIEW OF EMPIRICAL-STUDIES
LADDS, B; CONVIT, A
1994 FEB ;22(4):519-532, Bulletin of the American Academy of Psychiatry & the Law
Involuntary administration of antipsychotic medication to pretrial criminal defendants raises important and controversial questions. These questions arise especially with defendants who have been adjudicated as incompetent to stand trial and who require medication to be restored to trial-competency and return to face their pending criminal charges. This subject has been fiercely debated for decades, but it has received little empirical investigation. We review here the known empirical studies that have looked at the use of involuntary medication for this population of individuals. The following nine conceptual areas are explored: subject selection, definition of 'refusal' and related terms, frequency of refusal, characteristics of refusers, reasons for treatment, reasons for refusal, type and outcome of the review of the refusal, outcome of treatment in the hospital, and outcome of the criminal charges. Relevant findings are reviewed. Methodological limitations call for more research in this area
— id: 87415, year: 1994, vol: 22, page: 519, stat: Journal Article,

Hospitalized insanity acquittees' level of functioning
Shah PJ; Greenberg WM; Convit A
1994 ;22(1):85-93, Bulletin of the American Academy of Psychiatry & the Law
Since 1975 in New Jersey, similar legal criteria apply to the discharge of insanity acquittees as those patients who are civilly committed. Based on contact with insanity acquittees (NGRIs) in a regional state hospital, we had the impression that they appeared to be functioning better than the general inpatient population. The purpose of this study was to assess the length of inpatient stay and the level of functioning for the NGRIs and contrast it to a comparison group selected to for variables such as age, ethnicity, Axis I diagnosis, and history of substance abuse, which could impact on our variables of interest. We obtained psychiatrist-rated clinical global impression (CGI) scores and nursing-rated specific level of functioning (SLOF) scores in a group of 62 NGRIs and in a matched group of 62 controls. The NGRIs had significantly better CGI scores, and higher 'personal care skills' and 'social acceptability' SLOF section scores. The social acceptability subscale includes items for aggressiveness towards others, self, and property, all of which were significantly better for the NGRIs. Thus, in our setting, inpatient NGRIs displayed some evidence of better clinical functioning, including less perceived aggressiveness, than the control inpatients. Although the NGRIs has been in the regional state hospital for a shorter period than the controls, the NGRIs had spent an average of over three continuous years in secure facilities before transfer to the regional state hospital. We discuss our findings in view of high rates of paranoid subtypes of psychotic disorders among the NGRI group, and the high prevalence of substance abuse
— id: 60368, year: 1994, vol: 22, page: 85, stat: Journal Article,

Competency, civil commitment, and the dangerousness of the mentally ill
Bittman BJ; Convit A
1993 Nov;38(6):1460-1466, Journal of forensic sciences
The purpose of this study was to assess if a relationship exists between the nature of an individuals criminal charges and the finding of fitness among defendants evaluated at the Forensic Psychiatry Clinic servicing Manhattan. We examined the records of 354 defendants referred to the Forensic Clinic from the New York Criminal and Supreme Courts for a competency to stand trial evaluation. We reviewed their charges in light of the finding of competency. Incompetent defendants were most often accused of misdemeanors rather than felonies and of non-violent rather than violent crimes. Perhaps individuals who are thought to be psychiatrically disturbed get detained by the police on trivial charges so as to get them off the streets. Deinstitutionalization and civil commitment laws are considered as contributing factors and their impact is discussed
— id: 6326, year: 1993, vol: 38, page: 1460, stat: Journal Article,

Hippocampal atrophy in early Alzheimer's disease: anatomic specificity and validation
Convit A; de Leon MJ; Golomb J; George AE; Tarshish CY; Bobinski M; Tsui W; De Santi S; Wegiel J; Wisniewski H
1993 Winter;64(4):371-387, Psychiatric quarterly
We evaluated three groups of elderly individuals who were carefully screened to rule out clinically significant diseases that could affect cognition. They were matched for age and education. The groups included normals (N = 18), Alzheimer's Disease (AD) patients (N = 15), and minimally impaired individuals with memory complaints and impairments but who did not fulfill criteria for AD (N = 17). Volumetric measurements of different regions of the temporal lobe on the coronal scan as well as ratings of the perihippocampal cerebrospinal fluid (CSF) accumulation (HCSF) on the negative angle axial MR were carried out. Volume reductions were found in AD relative to the normals for both medial and lateral temporal lobe volumes. Only hippocampal volume reductions were found in the minimal group. The minimally impaired individuals had equivalent hippocampal volume reductions and significantly larger parahippocampal and lateral temporal lobe gyri than the AD group. The axial HCSF was validated using the coronal volumes. The combination of coronal hippocampal and perihippocampal CSF was the best predictor of the axial HCSF rating. The parahippocampal volume did not add to the predictive ability of the hippocampal-perihippocampal CSF combination. Future work should validate these findings with longitudinal designs as well as assess the issue of normal aging of these structures and their relationship to cognitive function
— id: 6340, year: 1993, vol: 64, page: 371, stat: Journal Article,

Measurement of medial temporal lobe atrophy in diagnosis of Alzheimer's disease
de Leon MJ; Golomb J; Convit A; DeSanti S; McRae TD; George AE
1993 Jan 9;341(8837):125-126, Lancet
— id: 9457, year: 1993, vol: 341, page: 125, stat: Journal Article,

The radiologic prediction of Alzheimer disease: the atrophic hippocampal formation
de Leon MJ; Golomb J; George AE; Convit A; Tarshish CY; McRae T; De Santi S; Smith G; Ferris SH; Noz M; et al
1993 Jul-Aug;14(4):897-906, AJNR. American journal of neuroradiology
PURPOSE: To test the hypothesis that atrophy of the hippocampal formation in nondemented elderly individuals would predict subsequent Alzheimer disease. METHOD: We studied 86 subjects at two time points, 4 years apart. At baseline all study subjects were nondemented and included 54 control subjects and 32 persons who had memory complaints and minimal cognitive impairments. All subjects received a CT scan using a protocol designed to image the perihippocampal cerebrospinal fluid (HCSF) accumulating in the fissures along the axis of the hippocampal formation. Blind to the clinical evaluations, we subjectively assessed the presence of HCSF at the baseline. Retrospectively, we examined the predicted association between baseline HCSF and clinical decline as determined across the two evaluations. RESULTS: At follow-up 25 of the 86 subjects had deteriorated and received the diagnosis of Alzheimer disease. Of the declining subjects, 23 came from the minimally impaired group, and 2 came from the control group. In the minimally impaired group the baseline HCSF measure had a sensitivity of 91% and a specificity of 89% as a predictor of decline. Both control subjects who deteriorated were also correctly identified at baseline. One of these two subjects died, and an autopsy confirmed the presence of Alzheimer disease. M(r) validation studies demonstrated that HCSF is quantitatively related to dilatation of the transverse fissure of Bichat and the choroidal and hippocampal fissures. CONCLUSION: Our findings strongly suggest that among persons with mild memory impairments, dilatation of the perihippocampal fissures is a useful radiologic marker for identifying the early features of Alzheimer disease
— id: 9456, year: 1993, vol: 14, page: 897, stat: Journal Article,

The disposition of criminal charges after involuntary medication to restore competency to stand trial
Ladds B; Convit A; Zito J; Vitrai J
1993 Nov;38(6):1442-1459, Journal of forensic sciences
The United States Supreme Court, in the recent case of Riggins v. Nevada, extended its examination of the issue of involuntary treatment with anti-psychotic medication to the mentally disabled facing criminal trial. Although this was an extreme case where the defendant faced a possible death sentence, the involuntary administration of anti-psychotic medication to restore 'competency to stand trial' always raises unique medical and moral questions. This highly controversial issue has received little empirical investigation. We report here on the first study to follow-up on the disposition of the criminal charges of persons committed to a hospital for the restoration of 'competency to stand trial' who refused anti-psychotic medication and for whom involuntary treatment was sought. We have previously reported on the characteristics of these cases (N = 68) and aspects of their outcome in the hospital. This cohort of patients represents virtually all indicted felony offenders in New York state who were incompetent to stand trial and for whom involuntary treatment with anti-psychotic medication was requested between 1986 and 1990. The present retrospective report focuses on the disposition of the criminal charges for such cases, in a state that does not have a death penalty. Tentative inferences are considered based on the findings that persons who were involuntarily restored to 'competency to stand trial' had a variety of dispositions of their criminal charges, including plea negotiations that resulted in foreshortened incarceration and several cases of insanity acquittals. Suggestions for further and more conclusive studies are proposed
— id: 6431, year: 1993, vol: 38, page: 1442, stat: Journal Article,

Dilatation of the lateral part of the transverse fissure of the brain in Alzheimer's disease
Narkiewicz O; de Leon MJ; Convit A; George AE; Wegiel J; Morys J; Bobinski M; Golomb J; Miller DC; Wisniewski HM
1993 ;53(3):457-465, Acta neurobiologiae experimentalis
Post-mortem MRI (magnetic resonance images) studies followed by histopathological examination were used to study the size and the shape of the lateral part of the transverse fissure of the brain in seven individuals with Alzheimer disease (AD) and five controls. In control brains, the lateral part of the transverse fissure is a narrow cleft protruding laterally as choroid and hippocampal recesses. In AD-affected brains, the lateral part of the transverse fissure becomes a large subarachnoid space as a result of different degrees of atrophy of various hippocampal and parahippocampal structures. Our findings directly indicate the relationship between changes in the hippocampal and parahippocampal structures and the size of the lateral part of the transverse fissure. Sector CA1, the subiculum, the entorhinal cortex, and the parahippocampal isocortex are the most affected, whereas the dentate gyrus is much less affected. Adjacent thalamic structures, which are less vulnerable to the AD pathology, do not appear to contribute to transverse fissure changes. The size and the shape of the lateral part of the transverse fissure of the brain in AD reflect the atrophy of the hippocampus and parahippocampal structures
— id: 9458, year: 1993, vol: 53, page: 457, stat: Journal Article,

Homelessness and the mentally ill offender
Richman BJ; Convit A; Martell D
1992 May;37(3):932-937, Journal of forensic sciences
This paper presents the results of a retrospective analysis of the discharge summaries of 69 mentally ill offenders. The subjects were patients in a New York State Psychiatric Hospital for a two-year period between January 1988 and December 1989 who were referred by the courts under New York State Criminal Procedure Law (CPL). The subjects were further compared as to homelessness at the time of the instant offense to study the association of this variable and criminal behavior among the mentally ill. Statistical analyses demonstrated significant relationships between variables of homelessness, prior offense history, and substance abuse
— id: 13599, year: 1992, vol: 37, page: 932, stat: Journal Article,

Assessment of risk behaviors for HIV infection among psychiatric inpatients
Volavka J; Convit A; O'Donnell J; Douyon R; Evangelista C; Czobor P
1992 May;43(5):482-485, Hospital & community psychiatry
A 13-item questionnaire was constructed to assess risk factors for HIV infection among 476 patients newly admitted over a one-year period to a state psychiatric hospital in New York City. Because psychopathology can affect patients' self-reports, the validity of the instrument was established by HIV antibody tests in a subset of 352 patients. Results of the questionnaire indicated that the 352 patients were almost equally divided between the high-risk and low-risk categories. HIV seroprevalence was .6 percent among the low-risk patients, but 14.4 percent among the high-risk patients. The findings suggest that a screening program to detect HIV-positive patients should be undertaken in this population, that it should be focused on the high-risk subgroup, and that the questionnaire can be used to define that subgroup. However, results of the study may not generalize to other geographic areas
— id: 61041, year: 1992, vol: 43, page: 482, stat: Journal Article,

Neuroleptic treatment, symptoms of schizophrenia, and plasma homovanillic acid concentrations revisited
Volavka J; Douyon R; Convit A; Czobor P; Cooper TB
1992 Dec;49(12):999-1000, Archives of general psychiatry
— id: 61039, year: 1992, vol: 49, page: 999, stat: Journal Article,

Psychobiology of the violent offender
Volavka J; Martell D; Convit A
1992 Jan;37(1):237-251, Journal of forensic sciences
The antecedents of violent crime may include childhood victimization, head injuries, and alcohol and drug abuse. Neuropsychological and neuropsychiatric findings suggest temporal and frontal lobe dysfunctions in violent offenders; these dysfunctions appear to be more pronounced in the dominant hemisphere. Recent studies implicate disturbances of central serotonergic functions in impulsive homicide and arson. These results provide an adequate rationale for larger interdisciplinary studies using neurochemical, neuropsychiatric/neuropsychological, and psychosocial methods on the same subjects
— id: 61043, year: 1992, vol: 37, page: 237, stat: Journal Article,

Lateralized abnormality in the EEG of persistently violent psychiatric inpatients
Convit A; Czobor P; Volavka J
1991 Aug 15;30(4):363-370, Biological psychiatry
Twenty-one consecutive right-handed male psychiatric inpatients treated on a unit designed for the management of violent behavior were given computerized EEGs. We recorded their violent behaviors, the number of staff interventions needed to control their behavior, and their medications. The number of instances of violence as well as the number of staff interventions were related to increased delta band activity and to decreased alpha band activity in the temporal and the parietooccipital areas. These relationships were independent of the current medications and of the length of stay on the special unit. Furthermore, our results demonstrate that violence is very significantly related to the hemispheric asymmetry in EEG for the frontotemporal derivations. With increased levels of violence there was a greater level of delta power in the left compared with the right
— id: 10341, year: 1991, vol: 30, page: 363, stat: Journal Article,

Type of symptomatology as a form of volunteer bias
Convit A; Levine S; Berns S; Evangelista C
1991 ;19(2):185-191, Bulletin of the American Academy of Psychiatry & the Law
We sought to explore the relationship between type of psychopathology and consent bias. Using the Brief Psychiatric Rating Scale we assessed a group of 48 forensic psychiatric inpatients. These patients were later independently approached by a researcher who attempted to get their consent for a study on the validity of self-reported criminal behavior. Thirty agreed to participate and 18 did not. The consenting patients were significantly younger and had significantly more negative symptoms than the nonconsenters. The difference in negative symptoms remained significant after age and medication dose, in chlorpromazine equivalents, were covaried out. The authors discuss the implications of these findings for forensic research
— id: 10342, year: 1991, vol: 19, page: 185, stat: Journal Article,

Videotape recording of assaults on a state hospital inpatient ward
Crowner ML; Douyon R; Convit A; Volavka J
1991 Spring;3(2):S9-14, Journal of neuropsychiatry & clinical neurosciences
— id: 61048, year: 1991, vol: 3, page: S9, stat: Journal Article,

Intentional ingestion of foreign objects by male prison inmates
Karp JG; Whitman L; Convit A
1991 May;42(5):533-535, Hospital & community psychiatry
— id: 14026, year: 1991, vol: 42, page: 533, stat: Journal Article,

HIV seroprevalence and risk behaviors in psychiatric inpatients
Volavka J; Convit A; Czobor P; Douyon R; O'Donnell J; Ventura F
1991 Nov;39(2):109-114, Psychiatry research
The seroprevalence of the human immunodeficiency virus (HIV) in 515 patients consecutively admitted to a state psychiatric hospital in New York City was 8.9%. There were 365 patients whose results were individually traceable; the remaining 150 patients were tested anonymously. Risk factors including parenteral drug abuse, male homosexual behaviors, and other sexual behaviors were studied in the traceable patients. Logistic regressions indicated that parenteral drug abuse was the main risk factor in both males and females. In females, two additional factors were significant: sex with parenteral drug users or with partners who have the acquired immunodeficiency syndrome (AIDS), and sex with bisexual men. Females with bipolar disorders were particularly likely to report sex with parenteral drug users or with partners who have AIDS
— id: 13853, year: 1991, vol: 39, page: 109, stat: Journal Article,

Characteristics of repeatedly assaultive psychiatric inpatients
Convit A; Isay D; Otis D; Volavka J
1990 Oct;41(10):1112-1115, Hospital & community psychiatry
Investigations of assaults in psychiatric hospitals have found that a small proportion of inpatients are responsible for a large percentage of the violence that occurs. In a large state hospital patients who were repeatedly violent (recidivists) were compared with patients who were violent only once or twice (nonrecidivists), and the relationships between repeatedly violent behavior and gender, age, and diagnosis were examined. All reports of violent incidents over a six-month period for a population of 1,552 inpatients--a total of 497 incidents involving 313 patients--were reviewed. Seventy patients were involved in three or more incidents each and were responsible for 53 percent of all violence. Recidivist men inflicted serious injuries at a rate ten times higher than that for all the other violent patients. Recidivist women were significantly younger than nonrecidivist assaultive women and were about the same mean age as the assaultive men. Recidivist women were also more likely to have organic brain disorder or personality disorder
— id: 61050, year: 1990, vol: 41, page: 1112, stat: Journal Article,

Validity of self-reports of criminal activity in psychiatric inpatients
Convit A; O'Donnell J; Volavka J
1990 Jan;178(1):48-51, Journal of nervous & mental disease
Self reports of criminal activity are known to be valid in general populations. Little is known about the validity of self-reports of crime in psychiatric inpatients. A group of 41 psychiatric inpatients had their self-reported arrests contrasted with their official arrest records. Sixty-six percent of the patients gave accurate reports. Twelve percent denied having arrests when their record showed arrests. Twenty-two percent reported arrests when their official records showed none. The authors discuss the implications of these findings
— id: 61054, year: 1990, vol: 178, page: 48, stat: Journal Article,

Akathisia and violence
Crowner ML; Douyon R; Convit A; Gaztanaga P; Volavka J; Bakall R
1990 ;26(1):115-117, Psychopharmacology bulletin
Akathisia is a common side effect of neuroleptic drugs that may present with behavioral disturbances. There have been preliminary reports on the association between violence and akathisia. We report the first observational study of this relationship. Patients studied were from a special unit for violent patients. A closed-circuit television camera was installed in each of the corners in its dayroom. Incidents of assault plus the 5 minutes preceding each assault were recorded on videotape. Participants and bystanders were rated for the motor component of akathisia. For each of nine incidents, we compared the akathisia scores for participants and for bystanders. Both victims and assailants were akathisic before about half of all incidents; bystanders rarely were. The classification of the movements we rated and the implications for further studies are discussed
— id: 21942, year: 1990, vol: 26, page: 115, stat: Journal Article,

Tryptophan treatment of aggressive psychiatric inpatients
Volavka J; Crowner M; Brizer D; Convit A; Van Praag H; Suckow RF
1990 Oct 15;28(8):728-732, Biological psychiatry
This double-blind, placebo-controlled study tested the effectiveness of tryptophan (TRP) in the treatment of aggressive psychiatric inpatients. After a baseline observation period of 1 month, patients were randomly assigned to treatment either with TRP (up to 6 g/day) or with placebo. There were 10 subjects in each treatment group. These treatments were administered for 25-35 days, after which the patients were observed for 1 month. Throughout this study, patients were receiving other medications. Injections of antipsychotics and sedatives were administered as needed to control agitated or violent behavior. Blood levels of TRP and other large neutral amino acids were obtained repeatedly, and ratios between TRP and other amino acids were computed. These analyses confirmed significant increases of TRP ratios in TRP-treated patients. TRP treatment had no effect on the number of violent incidents, but it significantly reduced the need for injections of antipsychotics and sedatives. The study thus provided indirect support for beneficial effects of TRP in aggressive psychiatric inpatients
— id: 61049, year: 1990, vol: 28, page: 728, stat: Journal Article,

Inpatient violence: trait and state
Krakowski MI; Convit A; Jaeger J; Lin S; Volavka J
1989 ;23(1):57-64, Journal of psychiatric research
This study compared patients who showed persistent violence, transient violence and no violence. The presence of neurological abnormalities was found to be the factor that differentiated most clearly among the three groups. The persistently violent patients, in addition to showing significantly more neurological abnormalities, also evidenced a more disturbed family background. Both violent groups had a higher incidence of violent crime prior to hospitalization than the nonviolent controls. A logistic regression model simultaneously relating the effects of six factors on violent behavior was developed and used to predict violent group membership
— id: 61058, year: 1989, vol: 23, page: 57, stat: Journal Article,

Neurological impairment in violent schizophrenic inpatients
Krakowski MI; Convit A; Jaeger J; Lin S; Volavka J
1989 Jul;146(7):849-853, American journal of psychiatry
This study relates violent behavior of schizophrenic inpatients to demographic, historical, EEG, neurological, and neuropsychological variables. Patients were classified into high (N = 28), low (N = 27), or no (N = 34) violence groups. There were no significant differences among the groups on demographic or historical variables, except for prevalence of violent crime, which was higher in both violent groups than in nonviolent patients. Neurological and neuropsychological abnormalities differentiated the groups, with the high violence group evidencing more abnormalities than the other two groups in the area of integrative sensory and motor functions. The authors suggest that violence as well as neurological and neuropsychological deficits may characterize a more severe form of schizophrenia
— id: 61057, year: 1989, vol: 146, page: 849, stat: Journal Article,

Videotape recording of inpatient assaults: a pilot study
Brizer DA; Crowner ML; Convit A; Volavka J
1988 Jun;145(6):751-752, American journal of psychiatry
Inpatient assaults were videotaped and then characterized by tape reviewers as showing high or low hostility. Over a 2-month period, the videotape reviewers documented more than twice as many high-hostility assaults as were documented by other methods of reporting
— id: 11076, year: 1988, vol: 145, page: 751, stat: Journal Article,

Underreporting of physical assaults in schizophrenic inpatients
Convit A; Isay D; Gadioma R; Volavka J
1988 Aug;176(8):507-509, Journal of nervous & mental disease
The authors followed prospectively a group of 79 newly admitted male schizophrenics for 6 months or until discharged, whichever came first, and monitored their assaultive behavior by review of their charts and the ward journals. Assaults were detected reliably by this method. When the assaultive behavior monitored in this way was contrasted with officially reported assaultiveness, 50% more assaults and 34.5% more patients who had one or more instances of assaultive behavior during the study period were detected. There were no differences in the number of injuries detected by the two methods. The authors contend that a realistic estimate of the incidence of physical assaults in young male schizophrenic inpatients is no less than 1.5 times that reflected by official reports
— id: 10992, year: 1988, vol: 176, page: 507, stat: Journal Article,

Predicting assaultiveness in psychiatric inpatients: a pilot study
Convit A; Jaeger J; Lin SP; Meisner M; Volavka J
1988 Apr;39(4):429-434, Hospital & community psychiatry
A sample of 87 psychiatric inpatients known to have been assaultive while in the hospital was contrasted with a matched group of nonviolent patients to identify the personal risk factors that distinguished the two groups. Data were collected using a personal history interview, a neurological examination, and an electroencephalogram. The four risk factors identified--neurological abnormality, history of violent crime, history of violent suicide attempts, and deviant family environment in childhood--were used to develop a statistical model predicting which subjects in a sample of newly admitted patients would become assaultive during the first three months after admission. The predicted classification of patients was found to be significantly related to subsequent assaultive behavior
— id: 61063, year: 1988, vol: 39, page: 429, stat: Journal Article,

History of phencyclidine use and repeated assaults in newly admitted young schizophrenic men
Convit A; Nemes ZC; Volavka J
1988 Sep;145(9):1176-1176, American journal of psychiatry
— id: 61061, year: 1988, vol: 145, page: 1176, stat: Journal Article,

Prediction of violence in psychiatric inpatients
Convit, Antonio; Jaeger, Judith; Shang, Pin Lin; Meisner, Morris; Volavka, Jan
Biological contributions to crime causation Dordrecht, Netherlands: Martinus Nijhoff Publishing, 1988,
(from the chapter) attempt to predict which patients . . . will become assaultive /// patient characteristics / demographic and clinical correlates / ecological and interpersonal correlates /// case-control study / cross-validation of discriminant factors
— id: 4793, year: 1988, vol: , page: 223, stat: Chapter,

A rating scale for reporting violence on psychiatric wards
Brizer DA; Convit A; Krakowski M; Volavka J
1987 Jul;38(7):769-770, Hospital & community psychiatry
— id: 61067, year: 1987, vol: 38, page: 769, stat: Journal Article,

Minor physical anomalies in violent adult inpatients
Crowner ML; Jaeger J; Convit A; Brizer D; Volavka J
1987 Sep;22(9):1166-1168, Biological psychiatry
— id: 11375, year: 1987, vol: 22, page: 1166, stat: Journal Article,