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Childhood sexual assault (CSA) victimization and depression are global public health concerns that disproportionately affect youths involved in the juvenile justice system. Little research has examined the influence of CSA on the stability of depressive symptoms among repeat juvenile offenders. The present study tested a gendered model of the association between lifetime CSA victimization and depression for three time points: baseline juvenile assessment entry; second reentry; and third reentry. Further, covariate analyses were conducted to explore the impact of socio-demographics on CSA victimization and depression. Results indicate that CSA victimization was associated directly with baseline depression and indirectly with depression at second reentry for both male and female justice-involved youths. For white, male youth, there were significantly higher rates of depression over time, than other males. However, age, African American or Hispanic race/ethnicity, living situation, and urbanity were not significantly associated with CSA victimization at baseline or depression over time. These findings underscore the need for juvenile justice services that address exposure to childhood trauma and mental illness more effectively.

Objective: Scant research exists on the validity of self-reported marijuana use using biological assays among adolescents involved in the juvenile justice system. This exploratory study examined gender (sex) differences in underreporting of marijuana use and the impact of age, race/ethnicity, living situation, depression, family problems, sexual risk behaviors, previous drug treatment, and juvenile justice placement. Methods: Self-reports of past year marijuana use were validated with urinalysis, and those testing positive for marijuana use were selected for study. The sample was 256 females and 885 males, aged 12 to 18, entering an urban juvenile assessment center in a southeastern U.S. state between 2017 and 2019. Results: Results indicated significant differences in marijuana underreporting (tested positive but self-reported no use), with 37% of females and 55% of males underreporting use. For males, Hispanic ethnicity, African American race, sexually transmitted infection (STI), and secure detention placement increased the odds of underreporting, while having an incarcerate parent and previous drug treatment decreased the odds. For females, number of sexual partners decreased the odds of underreporting of marijuana use. Conclusion: These findings imply use of collateral information, such as urine tests, as a recommendation for juvenile justice intake to corroborate self-reports and guide risk assessment.

Associations between high body mass index (BMI) and subsequent cognitive decline, reported in elderly averaging below age 75, become less consistent at older ages. We compared the associations of BMI with cognition in moderately old (ages 75–84, N = 154) and oldest-old (85+, N = 93) samples. BMI and cognition were assessed cross-sectionally in cognitively intact elderly (mean age = 84.5, SD = 4.4) male veterans. Regression analyses of three cognitive domains — executive functions/language, attention, and memory—compared relationship with BMI between the moderately old and oldest-old. Higher BMI was associated with relatively poorer executive functions/language performance in the moderately old, while the opposite relationship, higher BMI associated with relatively better performance, was found in the oldest-old. Associations for the other two cognitive domains did not differ significantly between age groups. The reversal of association direction for executive functions/language performance with higher BMI is consistent with the protected survivor model. This model posits a minority subpopulation with a protective factor—genetic or otherwise—against both mortality and cognitive decline associated with risk factor status. The very old who remain cognitively intact despite the presence of risk factors are more likely to possess protection.

Background: Type 2 diabetes (T2D) is a metabolic condition associated with poor clinical and cognitive outcomes including vascular disease, depressive symptoms, cognitive impairment, and dementia. In the general elderly population, depression has been consistently identified as a risk factor for cognitive impairment/decline. However, the association between depression and cognitive function in T2D has been understudied. Objective: We investigated the association between depression and cognitive function in a large sample of cognitively normal elderly with T2D. Methods: In this cross-sectional study, we examined 738 participants, aged 65–88 years old, enrolled in the Israel Diabetes and Cognitive Decline study. For each cognitive domain (Episodic Memory, Executive Function, Attention/Working Memory, Language/Semantic Categorization) and Overall Cognition, multiple linear regressions assessed its association with depression (score greater than 5 on the 15-item version of the Geriatric Depression Scale [GDS]), adjusting for age, sex, and education. Results: Depression (n = 66, 8.9%) was associated with worse performance on tasks of Executive Function (p = 0.004), Language/Semantic Categorization (p

Introduction Some associations of high total cholesterol with dementia risk diminish as the outcome age—age at cognitive assessment—increases. Methods The Framingham Heart Study provided 1897 participants with intact cognition at entry. Cox regression analysis for incident marked cognitive decline included "time-dependent" coefficients, with associations between total cholesterol and covariates changing by outcome age. Decline within age categories of 75–84 and 85–94 years was also examined. Results Significant associations of rising total cholesterol linear slope, low entry age, low education, and statin nonuse with risk diminished significantly by outcome age. At 85–94 years, falling linear slope was significant. Discussion The protected survival model posits a minority subpopulation with protection against mortality and cognitive decline associated with total cholesterol risk factors. It predicts the observed diminished or reversed cholesterol associations with increasing age. Protection is particularly likely for successful cognitive aging—intact cognition at very old age—despite increased risk from cholesterol.

Background Type 2 diabetes mellitus (T2DM) is prevalent in the general United States population, and in the veteran population. T2DM has consistently been linked to increased risk for cognitive impairment, dementia, and Alzheimer's disease. Computerized cognitive training (CCT) is practical and inexpensive cognitive interventions that is an alternative to medication. Objective To report the recruitment methods and challenges to date in an ongoing two-site randomized controlled trial (RCT) of CCT on cognitive function and T2DM management in an older non-demented veteran population. Methods Veterans are recruited primarily by targeted mailings or by direct contact at clinics and presentations. Results From 1,459 original contacts, 437 expressed initial interest, 111 provided informed consent, and 97 completed baseline assessments. Participants from the two VA Medical Centers differed in demographics and baseline characteristics. Comparing recruitment methods, the proportion of individuals contacted who were ultimately consented was significantly less from mailings (5%) than other sources (20%), primarily face- to-face clinic visits (χ2 (1) = 38.331, p Conclusions Mailings are cost-effective, but direct contact improved recruitment. Not using or lacking access to computers and ineligibility were major reasons for non-participation. Within-site comparisons of demographically diverse sites can address confounding of demographic and other site differences.

Introduction Waist circumference is associated with type 2 diabetes (T2D) and cognition, yet the relationship between waist circumference and cognition in individuals with T2D is not well understood. Methods We studied the relationship of waist circumference with five cognitive outcomes (executive functioning, language/semantic categorization, attention/working memory, episodic memory, and an overall cognition measure) in 845 cognitively normal elderly with type 2 diabetes (T2D). Results In women, waist circumference was correlated with significantly lower language and/or semantic categorization performance ( P P = .026), and overall cognition ( P = .003) after controlling for age, education, BMI, and cardiovascular, diabetes-related, APOE e4, and inflammatory potential confounders. Attention/working memory ( P = .532) and episodic memory ( P = .144) were not associated with waist circumference. These correlations were not found in men. Discussion These results suggest that central adiposity in elderly women with T2D may increase their risk for dementia.

No pharmacological treatments have been demonstrated to effectively treat chronic multisymptom illness (CMI) in Gulf War veterans (GWV). This study assessed the effect of the glucocorticoid receptor antagonist mifepristone in GWV with CMI. A randomized, double-blind, cross-over trial of mifepristone, with two six-week treatment phases separated by a one-month washout period, was conducted at a Veterans Affairs (VA) hospital between 2008 and 2011. Participants were randomized to receive either 200mg of mifepristone per day or matched placebo first. The primary clinical outcome measure was change in self-reported physical health. Neurocognitive functioning and self-reported measures of depression, PTSD, and fatigue were secondary outcomes. Sixty-five participants enrolled, of whom 36 were randomized and 32 (mean age, 49.1 (7.2) years) completed the study. Physical and mental health status and neurocognitive functioning were poor at baseline. Mifepristone treatment was not associated with improvement in self-reported physical health (p=0.838) or in other self-reported measures of mental health. Mifepristone treatment was significantly associated with improvements in verbal learning (p=0.008, d=0.508), in the absence of improvement in other cognitive measures (working memory (p=0.914), visual learning (p=0.643) and a global composite measure (p=0.937). Baseline morning cortisol levels and lysozyme IC50-DEX, a measure of peripheral glucocorticoid sensitivity, displayed a significant relationship with endpoint verbal learning scores (p=0.012 and p=0.007, respectively). The magnitude of cortisol change during treatment mediated the improvement in verbal learning. This study was negative for the primary and secondary clinical outcomes. However, the data suggest a moderate dose of mifepristone may have circumscribed cognitive-enhancing effects in CMI. Further study is warranted to determine whether and through which mechanisms mifepristone treatment can yield clinically meaningful improvement in cognitive function in CMI or other neuropsychiatric conditions associated with HPA axis dysregulation.

Summary There is growing evidence of the involvement of advanced glycation end products (AGEs) in the pathogenesis of neurodegenerative processes including Alzheimer's disease (AD) and their function as a seed for the aggregation of Aβ, a hallmark feature of AD. AGEs are formed endogenously and exogenously during heating and irradiation of foods. We here examined the effect of a diet high in AGEs in the context of an irradiated diet on memory, insoluble Aβ42, AGEs levels in hippocampus, on expression of the receptor for AGEs (RAGE), and on oxidative stress in the vasculature. We found that AD‐like model mice on high‐AGE diet due to irradiation had significantly poorer memory, higher hippocampal levels of insoluble Aβ42 and AGEs as well as higher levels of oxidative stress on vascular walls, compared to littermates fed an isocaloric diet. These differences were not due to weight gain. The data were further supported by the overexpression of RAGE, which binds to Aβ42 and regulates its transport across the blood–brain barrier, suggesting a mediating pathway. Because exposure to AGEs can be diminished, these insights provide an important simple noninvasive potential therapeutic strategy for alleviating a major lifestyle‐linked disease epidemic.

Justice-involved youth display higher prevalence rates of sexually transmitted diseases (STDs), in comparison with youth in the general population, highlighting a critical public health concern. Individual factors are important predictors of STDs, but only provide a partial understanding of this public health issue. Communities experiencing higher levels of disorder and lower levels of cohesion tend to have fewer institutional resources available, which may impact sexual risk behavior and STDs. However, few studies have examined the association between community characteristics and STD prevalence among adolescents. The current study examined community-level (n = 106) characteristics and individual-level attributes in explaining STDs among justice-involved youth (n = 1233: n = 515 female; n = 718 male). At the individual level, results showed older males and those with more drug-related problems were more likely to be STD positive, while females with more sexual partners and those with less drug-related problems were more likely to be STD positive. At the community level, females residing in areas with fewer educated residents were more likely to be STD positive. These gender differences were significant, suggesting a gendered perspective is important for understanding STD infection. The justice system represents a critical opportunity in the treatment and prevention of STDs for youth.

To study the association of dementia with apolipoprotein E-e4 (APOE-e4) and its interaction with age in a nonagenarian Costa Rican group (N-sample) and a general elderly contrast group (GE-sample). In both case-control studies, participants were cognitively intact or diagnosed with dementia. The N-sample (N = 112) was at least age 90 years; the GE-sample (N = 98) was at least age 65 years. Dementia and APOE-e4 were not significantly associated in the N-sample, but were in the GE-sample. There was a significant interaction of age with APOE-e4 in the N-sample, but not in the GE-sample. Descriptively dividing the N-sample at the median (age 93 years) showed a group interaction: APOE-e4 was more associated with dementia in the younger N-sample than in the older N-sample, where six of seven APOE-e4 carriers were cognitively intact. The results support the reduction in association of APOE-e4 with dementia in extreme old age, consistent with a survivor effect model for successful cognitive aging. Universidad de Costa Rica/[]/UCR/Costa Rica Fogarty International Center/[]/NIH/Estados Unidos National Institute on Aging/[R21TW009258]/NIH/Estados Unidos Alzheimer’s Association/[]//Estados Unidos UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Neurociencias (CIN) UCR::Vicerrectoría de Docencia::Salud::Facultad de Medicina::Escuela de Medicina UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigación en Biología Celular y Molecular (CIBCM) UCR::Vicerrectoría de Docencia::Ciencias Básicas::Facultad de Ciencias::Escuela de Biología

Research indicates at-risk youth are more likely to experience emotional and psychological problems. Young people who are often truant from school represent a group of at-risk youth, but one for which mental health issues are understudied. This study examined heterogeneity of mental health problems among a sample of 300 truant adolescents using latent class analysis (LCA). LCA indicated the sample of truants was best represented by four latent subgroups of youth with: low mental health problems; high depression, low mania; high mania, low depression; and high depression and mania. These subgroups were examined in relation to socio-demographic and psychosocial measures at baseline and after truancy offenses. Results indicated general and unique differences in these covariates across the four latent classes. Service and practice implications of better understanding mental health issues of truant youth are discussed.

OBJECTIVE This study aimed to analyze the relationship of variability in hemoglobin A1c (HbA1c) over years with subsequent depressive symptoms. RESEARCH DESIGN AND METHODS Subjects (n = 837) were participants of the Israel Diabetes and Cognitive Decline (IDCD) study, which aimed to examine the relationship of characteristics of long-term type 2 diabetes with cognitive decline. All pertain to a diabetes registry established in 1998, which contains an average of 18 HbA1c measurements per subject. The results presented here are based on the IDCD baseline examination. Symptoms of depression were assessed using the 15-item version of the Geriatric Depression Scale (GDS). To quantify the association between variability in glycemic control (measured as the SD of HbA1c measurements [HbA1c-SD]) since 1998 with the number of depression symptoms at IDCD baseline, incidence rate ratios (IRRs) and corresponding 95% CIs were estimated via negative binomial regression modeling and used to account for the overdispersion in GDS scores. RESULTS Subjects’ ages averaged 72.74 years (SD 4.63 years), and the mean number of years in the diabetes registry was 8.7 (SD 2.64 years). The mean GDS score was 2.16 (SD 2.26); 10% of subjects had a GDS score ≥6, the cutoff for clinically significant depression. Mean HbA1c significantly correlated with HbA1c-SD (r = 0.6625; P < 0.0001). The SD, but not the mean, of HbA1c measurements was significantly associated with the number of subsequent depressive symptoms. For each additional 1% increase in HbA1c-SD, the number of depressive symptoms increased by a factor of 1.31 (IRR = 1.31 [95% CI 1.03–1.67]; P = 0.03). CONCLUSIONS Variability in glycemic control is associated with more depressive symptoms.

To find associations of age, sex, and education with neuropsychological test performance in cognitively normal Spanish-speaking Costa Rican nonagenarians with little education; to provide norms; and to compare their performance with similar Puerto Ricans. For 95 Costa Ricans (90–102 years old, 0–6 years of education), multiple regression assessed associations with demographics of performance on six neuropsychological tests. Analyses of covariance compared them with 23 Puerto Ricans (90–99 years old). Younger age and being female—but not education—were associated with better performance on some neuropsychological tests, in particular episodic memory. The Puerto Ricans performed better on learning and memory tasks. In cognitively intact Spanish-speaking nonagenarians with little or no education, education did not affect test performance. Additional studies of the effect of education on cognitive performance are warranted in other samples with extremely low education or old age. National differences in performance highlight the importance of group-specific norms. National Institutes of Health/[R21TW009258]/NIH/Estados Unidos Universidad de Costa Rica/[]/UCR/Costa Rica Alzheimer’s Association/[]//Estados Unidos UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigación en Biología Celular y Molecular (CIBCM) UCR::Vicerrectoría de Docencia::Ciencias Básicas::Facultad de Ciencias::Escuela de Biología

The objective of this study was to test the hypothesis that corticosteroid and nonsteroidal anti-inflammatory drug (NSAID) medications are associated with less global and regional Alzheimer's disease (AD) neuropathology. This postmortem study was based on 694 brains of subjects from the Mount Sinai School of Medicine Brain Bank who did not have neuropathologies other than neuritic plaques (NPs), neurofibrillary tangles (NFTs), or cerebrovascular disease. Densities of NPs and of NFTs were assessed in several neocortical regions and in the hippocampus, entorhinal cortex, and amygdala. Counts of NPs in several neocortical regions were also assessed. For each neuropathology measure, analyses of covariance controlling for age at death and sex compared subjects who received only corticosteroids (n = 54) or those who received only NSAIDs (n = 56) to the same comparison group, subjects who received neither (n = 576). Subjects receiving corticosteroids had significantly lower ratings and counts of NPs for all neuropathological measures, and NFTs overall and in the cerebral cortex and amygdala. In contrast, no measures were significant for subjects who received NSAIDs. Use of corticosteroids was associated with approximately 50% fewer NPs and NFTs in most brain regions examined, compared with nonmedicated subjects. In contrast, use of NSAIDs was not substantially associated with the reductions in hallmark lesions of AD. Because corticosteroids have anti-inflammatory as well as a myriad of other neurobiological effects, more direct studies in model systems could reveal novel therapeutic targets and mechanisms for AD lesion reduction.

Cardiovascular risk factors including hypertension (HTN) have been shown to increase the risk of Alzheimer disease. The current study investigated whether individuals with HTN are more susceptible to increased cognitive decline and whether the influence of HTN on cognitive decline varied as a function of dementia severity. A total of 224 nursing home and assisted living residents, with a mean age of 84.9 (±7.6) years, were assessed longitudinally with Mini Mental State Exams (MMSEs) and Clinical Dementia Ratings (CDR). Baseline dementia status was defined by the CDR score. As described in Table 2, MMSE scores in persons with HTN and questionable dementia (CDR = 0.5) declined significantly faster than nonhypertensive questionably demented persons. Hypertensive participants did not decline significantly faster than nonhypertensive participants in persons with intact cognition (CDR = 0) or frank dementia (CDR ≥ 1). These results suggest an increased risk of subsequent cognitive decline in hypertensive individuals who are especially vulnerable to developing dementia and raises the possibility that avoiding or controlling HTN might reduce the rate of cognitive decline in cognitively vulnerable individuals, potentially delaying their conversion to full-fledged dementia.

De novo events appear more common in female and simplex autism spectrum disorder (ASD) cases and may underlie greater ASD risk in older fathers’ offspring. This study examined whether advancing paternal age predicts an increase in simplex ( n = 90) versus multiplex ASD cases ( n = 587) in 677 participants (340 families). Whether or not controlling for maternal age, results support a significant interaction of linear paternal age and sex of the child on simplex family type. Female ASD cases were significantly more likely to be simplex as paternal age increased, but the increase for males was not significant. Findings suggest that ASD arising from non-familial, de novo events may be far less prominent in males than in females, even if more prevalent in males, due to the substantially larger number of male cases attributable to other, more strongly male-biased risk factors.

We recently reported that serum methylglyoxal (sMG) is associated with a faster rate of decline in a global measure of cognition in the very elderly. We here provide for the first time evidence in which high levels of dietary AGE (dAGE) are associated with faster rate of decline in memory in 49 initially non-demented young elderly (p=0.012 in mixed regression models adjusting for sociodemographic and cardiovascular factors). Since modifying the levels of AGEs in the diet may be relatively easy, these preliminary results suggest a simple strategy to diminish cognitive compromise in the elderly and warrant further investigation.

Background The AMACR gene is located in the schizophrenia susceptibility locus on chromosome 5p13, previously identified in a large Puerto Rican pedigree of Spanish origin. The AMACR-encoded protein is an enzyme involved in the metabolism of branched-chain fatty and bile acids. The enzyme deficiency causes structural and functional brain changes, and disturbances in fatty acid and oxidative phosphorylation pathways observed in individuals with schizophrenia. Therefore, AMACR is both a positional and functional candidate gene for susceptibility to schizophrenia. Methods The study had a two-step design: we performed mutation analysis of the coding and flanking regions of AMACR in affected members of the pedigree, and tested the detected sequence variants for association with schizophrenia in a Puerto Rican case-control sample ( n = 383) of Spanish descent. Results and conclusion We identified three missense variants segregating with the disorder in the family, rs2278008, rs2287939 and rs10941112. Two of them, rs2278008 and rs2287939, demonstrated significant differences in genotype ( P = 4 × 10–4, P = 4 × 10–4) and allele ( P = 1 × 10–4, P = 9.5 × 10–5) frequencies in unrelated male patients compare to controls, with the odds ratios (OR) 2.24 (95% CI: 1.48–3.40) and 2.25 (95% CI: 1.49–3.38), respectively. The G–C–G haplotype of rs2278008-rs2287939-rs10941112 revealed the most significant association with schizophrenia ( P = 4.25 × 10–6, OR = 2.96; 95% CI: 1.85–4.76) in male subjects. There were no statistically significant differences in genotype, allele, and haplotype frequencies between female schizophrenia subjects and controls. Our results suggest that AMACR may play a significant role in susceptibility to schizophrenia in male patients.

To gain insight into ATP-binding cassette transporter A1 (ABCA1) function and its potential role in AD pathology, we analyzed the expression of the cholesterol transporter ABCA1 in postmortem hippocampus from persons at different stages of dementia and AD associated neuropathology relative to cognitively intact normal donors by quantitative polymerase chain reaction (qPCR) and Western blot. In this study clinical dementia rating (CDR) scores were used as a measure of dementia severity, whereas, Braak neuropathological staging and neuritic plaque density were used as an index of the neuropathological progression of AD. Correlation analysis showed that ABCA1 mRNA expression was significantly elevated at the earliest recognizable stage of dementia compared to persons with intact cognition. ABCA1 mRNA was also positively correlated with Braak neuropathological stages and neuritic plaque density counts. Additionally, ABCA1 mRNA levels showed robust correlation with dementia severity even after controlling for the confounding contribution of accompanying neuropathological parameters to ABCA1 mRNA expression. Western blot analyses showed that the differential expression observed at the transcriptional level is also reflected at the protein level. Thus, our study provides transcriptional and translational evidence that the expression of ABCA1, a key modulator of cholesterol transport across the plasma membrane, is dysregulated in the AD brain and that this dysregulation is associated with increasing severity of AD, whether measured functionally as dementia severity or neuropathologically as increased neuritic plaque and neurofibrillary tangle density.

Background The mini-mental state exam (MMSE) has been used to address questions such as determination of appropriate cutoff scores for differentiation of individuals with intact cognitive function from patients with dementia and rate of cognitive decline. However, little is known about the relationship of performance in specific cognitive domains to subsequent overall decline. Objective To examine the specific and/or combined contribution of four MMSE domains (orientation for time, orientation for place, delayed recall, and attention) to prediction of overall cognitive decline on the MMSE. Methods Linear mixed models were applied to 505 elderly nursing home residents (mean age = 85, > 12 years education = 27%; 79% F, mean follow-up = 3.20 years) to examine the relationship between baseline scores of these domains and total MMSE scores over time. Results Orientation for time was the only domain significantly associated with MMSE decline over time. Combination of poor delayed recall with either attention or orientation for place was associated with significantly increased decline on the MMSE. Conclusions The MMSE orientation for time predicts overall decline on MMSE scores over time. A good functioning domain added to good functioning delayed recall was associated with slower rate of decline. Copyright © 2009 John Wiley & Sons, Ltd.

Background Although genetic risk factors for posttraumatic stress disorder (PTSD) in similarly traumatized cohorts can be confounded with risk for type of exposure, the primary risk for exposure to the 9/11 attack on New York City was proximity, allowing study of PTSD risk in a sample that is not confounded by exposure-related risk. Methods Thirty-five Caucasians (15 with PTSD, stratified for exposure, age, and gender) were selected from a population-representative sample of persons exposed to the attack from which longitudinal data had been collected in four previous waves. Whole blood gene expression and cortisol levels were obtained. Results Seventeen probe sets were differentially expressed in PTSD. Identified genes were generally involved in hypothalamic-pituitary-adrenal (HPA) axis, signal transduction, or brain and immune cell function. FKBP5, a modulator of glucocorticoid receptor (GR) sensitivity, showed reduced expression in PTSD, consistent with enhanced GR responsiveness. FKBP5 expression was predicted by cortisol when entered with PTSD severity in regression analysis. Quantitative polymerase chain reaction confirmed significant reductions in FKBP5. Also less expressed in PTSD were STAT5B, a direct inhibitor of GR, and major histocompatibility complex (MHC) Class II. Conclusions Consistent with observations of HPA axis dysfunction in PTSD, several genes involved in glucocorticoid signaling are differentially expressed among those with current PTSD.

Objective: In animal models, early life exposure to major environmental challenges such as malnutrition and stress results in persisting cardiometabolic, neuroendocrine and affective effects. While such effects have been associated with pathogenesis, the widespread occurrence of 'developmental programming' suggests it has adaptive function. Glucocorticoids may mediate 'programming' and their metabolism is known to be affected by early life events in rodents. To examine these relationships in humans, cortisol metabolism and cardiometabolic disease manifestations were examined in Holocaust survivors in relation to age at exposure and affective dysfunction, notably lifetime posttraumatic stress disorder (PTSD).Methods: Fifty-one Holocaust survivors and 22 controls without Axis I disorder collected 24-h urine samples and were evaluated for psychiatric disorders and cardiometabolic diagnoses. Corticosteroids and their metabolites were assayed by gas chromatography-mass spectroscopy (GC-MS); cortisol was also measured by radioimmunoassay (RIA).Results: Holocaust survivors showed reduced cortisol by RIA, and decreased levels of 5 alpha-tetrahydrocortisol (5 alpha-THF) and total glucocorticoid production by GC-MS. The latter was associated with lower cortisol metabolism by 5 alpha-reductase and 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) type-2. The greatest decrements were associated with earliest age of Holocaust exposure and less severe PTSD symptomatology. Cardiometabolic manifestations were associated with decreased 11 beta-HSD-2 activity. In controls, 5 alpha-reductase was positively associated with trauma-related symptoms (i.e., to traumatic exposures unrelated to the Holocaust).Conclusion: Extreme malnutrition and related stress during development is associated with long-lived alterations in specific pathways of glucocorticoid metabolism. These effects may be adaptive and link with lower risks of cardiometabolic and stress-related disorders in later life. Published by Elsevier Ltd.

The male-to-female (M:F) ratio for autism spectrum disorders (ASD), typically about 4:1, appears to decrease with increasing paternal age, but this relationship has not been systematically tested. With 393 ASD cases from families with two or more ASD cases, we categorized paternal age into five age groups (

This study determined (a) the association between stages of Alzheimer's disease (AD) and overall gene expression change, and (b) brain regions of greatest vulnerability to transcriptional change as the disease progressed. Fifteen cerebrocortical sites and the hippocampus were examined in persons with either no cognitive impairment or neuropathology, or with only AD-associated lesions. Cases were stratified into groups of 7-19 based on the degree of cognitive impairment (clinical dementia rating scale, CDR); neurofibrillary tangle distribution and severity (Braak staging) or density of cerebrocortical neuritic plaque (NP; grouping by NP density). Transcriptional change was assessed by Affymetrix U133 mRNA microarray analysis. The results suggested that (a) gene expression changes in the temporal and prefrontal cortices are more closely related to disease severity than other regions examined; (b) more genes are down-regulated at any given disease severity stage than up-regulated; (c) the degree of gene expression change in a given regions depends on the disease severity classification scheme used; and (d) the classification of cases by CDR provides a more orderly gradient of gene expression change in most brain regions than Braak staging or NP grouping.

High rates of infection for chlamydia and gonorrhea have been noted among youths involved in the juvenile justice system. Although both individual and community-level factors have been found to be associated with sexually transmitted disease (STD) risk, their relative importance has not been tested in this population. A two-level logistic regression analysis was completed to assess the influence of individual-level and community-level predictors on STD test results among arrested youths processed at a centralized intake facility. Results from weighted two level logistic regression analyses (n = 1,368) indicated individual-level factors of gender (being female), age, race (being African American), and criminal history predicted the youths' positive STD status. For the community-level predictors, concentrated disadvantage significantly and positively predicted the youths' STD status. Implications of these findings for future research and public health policy are discussed.

Background: Studies of associations between serum lipids and Alzheimer’s disease (AD) or other dementias in the elderly show conflicting results, perhaps due to misclassification of the various dementias. Methods: For 358 nursing home residents, serum lipids were studied at admission and diagnoses established at autopsy. We used defined neuropathological criteria to distinguish the presence of AD and to avoid errors of clinical dementia assessment. Results: Residents with any AD pathology, as compared to those without AD pathology, had higher mean serum total cholesterol (TC; 200.4 vs. 185.9 mg/dl; p = 0.02) and higher mean low-density lipoprotein cholesterol (LDL; 124.5 vs. 111.5 mg/dl; p = 0.03). Further, mean TC, LDL and high-density lipoprotein cholesterol levels all increased progressively with increasing pathological certainty of AD (p for trend = 0.001, 0.02 and 0.02). Conclusions: TC and LDL were significantly related to pathologically defined AD. If serum lipids have a role in the pathogenesis of AD, interventions may modify the course of disease.

SIR—A possible role of inflammation in the development of dementia [1] has led to investigations examining whether C-reactive protein (CRP), a systemic marker of inflammation, is associated with worse cognitive function and decline in old age. Elevated CRP has been associated with worse global and specific cognitive functioning [2–7], although other studies have found no relationship between CRP and cognition [8–10]. Most studies have examined samples averaging

Background A significant association between parental PTSD and the occurrence of PTSD in offspring has been noted, consistent with the idea that risk for the development of PTSD is transmitted from parent to child. Two recent reports linking maternal PTSD and low offspring cortisol prompted us to examine the relative contributions of maternal vs. paternal PTSD in the prediction of PTSD and other psychiatric diagnoses in offspring. Methods One hundred seventeen men and 167 women, recruited from the community, were evaluated using a comprehensive psychiatric battery designed to identify traumatic life experiences and lifetime psychiatric diagnoses. 211 of these subjects were the adult offspring of Holocaust survivors and 73 were demographically comparable Jewish controls. Participants were further subdivided based on whether their mother, father, neither, or both parents met diagnostic criteria for lifetime PTSD. Results A higher prevalence of lifetime PTSD, mood, anxiety disorders, and to a lesser extent, substance abuse disorders, was observed in offspring of Holocaust survivors than controls. The presence of maternal PTSD was specifically associated with PTSD in adult offspring of Holocaust survivors. However, other psychiatric diagnoses did not show specific effects associated with maternal PTSD. Conclusion The tendency for maternal PTSD to make a greater contribution than paternal PTSD to PTSD risk suggests that classic genetic mechanisms are not the sole model of transmission, and paves way for the speculation that epigenetic factors may be involved. In contrast, PTSD in any parent contributes to risk for depression, and parental traumatization is associated with increased anxiety disorders in offspring.

Objective: To examine the association between treatment for diabetes and Alzheimer disease (AD) neuropathology. Methods: This postmortem study matched 124 subjects with diabetes to 124 without diabetes from the Mount Sinai School of Medicine Brain Bank, on age (mean = 81.2 + 9.3), sex (57.3% F), and severity of dementia (Clinical Dementia Rating [CDR] 2.4 + 1.7). Densities of neuritic plaques (NPs) and of neurofibrillary tangles (NFTs) were assessed in several neocortical regions and in the hippocampus, entorhinal cortex, and amygdala. Diabetic subjects were classified according to their recorded lifetime antidiabetic medications: none (n = 29), insulin only (n = 49), diabetes medications other than insulin only (n = 28), or concomitant use of both insulin and any oral antidiabetic medications (n = 18). For each dependent variable, analysis of covariance controlling for age at death, sex, and CDR distinguished among the nondiabetic patients and four diabetic subgroups. Results: There were differences among the five groups for NP ratings in the entorhinal cortex ( p = 0.003), amygdala ( p = 0.009), and overall NP ( p = 0.014) as well as counts of NPs in all regions examined ( p values ranging from 0.009 to 0.04). NP ratings in the hippocampus ( p = 0.057) and the combined neocortical measure ( p = 0.052) approached significance. In each analysis, the concomitant medication group had significantly fewer NPs (∼20%) than any of the other groups, which were relatively similar. No significant NFT differences were found. Conclusion: The results of this study suggest that the combination of insulin with other diabetes medication is associated with substantially lower neuritic plaque density consistent with the effects of both on the neurobiology of insulin.

Aims: To assess the relationships between early and late antemortem measures of dementia severity and Alzheimer disease (AD) neuropathology severity. Methods: 40 residents of a nursing home, average age at death 82.0, participated in this longitudinal cohort study with postmortem assessment. Severity of dementia was measured by Clinical Dementia Rating (CDR) at two time points, averaging 4.5 and 1.0 years before death. Densities of postmortem neuritic plaques (NPs) and neurofibrillary tangles (NFTs) were measured in the cerebral cortex, hippocampus, and entorhinal cortex. Results: For most brain areas, both early and late CDRs were significantly associated with NPs and NFTs. CDRs assessed proximal to death predicted NFTs beyond the contribution of early CDRs. NPs were predicted by both early and late CDRs. NPs were predictive of both early and late CDRs after controlling for NFTs. NFTs were only associated significantly with late CDR in the cerebral cortex after controlling for NPs. Conclusions: Even if assessed several years before death, dementia severity is associated with AD neuropathology. NPs are more strongly associated with dementia severity than NFTs. NFTs consistently associate better with late than early CDR, suggesting that these neuropathological changes may occur relatively later in the course of the disease.

Survival from Alzheimer's disease (AD) and other dementias into late old age may be a useful phenotype for genetic studies of successful cognitive aging. To support molecular genetics studies for successful cognitive aging, we conducted a two-stage study to determine an optimal age phenotype for successful cognitive aging. First, risk of AD was evaluated, through informant interviews, in 4,794 parents and siblings of 976 elderly nondemented probands who were divided into three different proband age groups: those aged 60-74, 75-89, and 90+. Relatives of probands aged 90+ had a significantly lower risk than the relatives of the other two proband groups. Second, this sample was combined with an earlier sample (combined nondemented elderly probands: n = 2,025; relatives: n = 10,506), and a series of proband age groups (i.e., 75-79, 80-84, 85-89, 90+) were used to determine which optimally identifies a group of relatives with low AD risk. Using the relatives of the nondemented proband aged 60-74 as the reference group, there were reductions in cumulative risk among relatives of probands aged 85-89 and 90+, but only the latter group also showed significant reductions to the relatives of probands aged 75-79, 80-84, and 85-89. This pattern of results varied little by sex. Finally, cumulative AD risk curves were similar between relatives of probands aged 90-94 and 95+. These results suggest that age 90 is an optimal age threshold to use for both men and women in genetic studies seeking to identify genes associated with successful cognitive aging.

Life expectancy is a familial trait. However, the effectiveness of using the age at death of a deceased parent to estimate life expectancy in their offspring can vary depending on whether death in the parent was due to extrinsic versus intrinsic causes, as well as demographic characteristics such as sex. While Alzheimer’s disease (AD) risk increases with increased age, mortality for individuals with AD is increased in contrast to comparably aged individuals without AD. Yet in most cases it is not the defining neuropathology of AD that directly terminates life but instead conditions and illnesses extrinsic to AD pathology that nevertheless have increased likelihood in its presence. For this reason, we hypothesized that offspring of AD mothers would have greater longevity than offspring of mothers without AD (insufficient numbers prevented a comparable analysis using fathers with AD). The longevity of 345 offspring of 100 deceased 60+ year old AD mothers was compared with 5,465 offspring in 1,312 deceased 60+ year old non-AD mothers. We used a proportional hazards model that accounted for clustered (nonindependent) observations due to the inclusion of several offspring from the same family. In both an unadjusted model and one that adjusted for the age at death in the mother, and the sex and birth year in the offspring we found evidence for increased longevity in the offspring of AD mothers. The results suggest that, in addition to genes that might directly affect pathways leading to AD, there may be familial/genetic factors not connected to specific pathophysiological processes in AD but instead associated with increased longevity that contribute to the familial aggregation observed in AD.

Objective: The authors examined instances of past sexual abuse and related demographic characteristics in the self-reports of a select group of married observant Jewish women. Methods: Orthodox Jewish married women (N=380) ages 19 to 58 responded to advertisements asking them to complete an anonymous questionnaire about sexual experiences, including sexual abuse. Results: Sexual abuse was reported by 26% of the respondents surveyed, with 16% reporting abuse occurring by the age of 13. More ultra-Orthodox Jews reported abuse than modern-Orthodox Jews. Women who were raised observant reported significantly less childhood sexual abuse than those who became observant later in life. Sexual abuse was associated with increased treatment-seeking for depression, marital counseling, or other emotional or psychological problems. Conclusion: While observant Jewish women live in a culture defined by a high degree of adherence to specific laws of conduct, including rules designed to regulate sexual contact, sexual abus...

To investigate the longitudinal course of mean 24-hour urinary cortisol excretion in posttraumatic stress disorder (PTSD), the authors evaluated 24-hour cortisol excretion in 28 Holocaust survivors 10 years after obtaining an initial estimate. Cortisol levels increased in participants whose PTSD had remitted (n = 3) but declined in participants who developed PTSD (n = 3) or whose PTSD status did not change over time (PTSD+: n = 14, PTSD-: n = 8). Cortisol levels at Time 1 predicted diagnostic status change better than psychological variables, including exposure to traumatic events between assessments. The authors conclude that cortisol levels are affected by change in PTSD status and age.

In recent years, several promising susceptibility loci for late-onset Alzheimer's disease (AD) were discovered, by implementing genome-wide association studies (GWAS) approach. Recent GWAS meta-analysis has demonstrated the association of 19 loci (in addition to the APOE locus) with AD in the European ancestry population at genome-wide significance level. Since Type 2 Diabetes (T2D) is a substantial risk factor for cognitive decline and dementia, the 19 single nucleotide polymorphisms (SNPs) that represent the 19 AD loci were studied for association with performance in episodic memory, a primary cognitive domain affected by AD, in a sample of 848 cognitively normal elderly Israeli Jewish T2D patients. We found a suggestive association of SNP rs6733839, located near the bridging integrator 1 (BIN1) gene, with this phenotype. Controlling for demographic (age, sex, education, disease duration and ancestry) covariates, carriers of two copies of the AD risk allele T (TT genotype) performed significantly worse (p=0.00576; p=0.00127 among Ashkenazi origin sub-sample) in episodic memory compared to carriers of the C allele (CT+CC genotypes). When including additional potential covariates (clinical and APOE genotype), results remained significant (p=0.00769; p=0.00148 among Ashkenazi). Interestingly, as validated in multiple large studies, BIN1 is one of the most established AD risk loci, with a high odds ratio. Although preliminary and require further replications, our findings support a contribution of BIN1 to individual differences in episodic memory performance among T2D patients.

The haptoglobin (Hp) genotype has been associated with cognitive function in type 2 diabetes. Because ethnicity/culture has been associated with both cognitive function and Hp genotype frequencies, we examined whether it modulates the association of Hp with cognitive function.This cross-sectional study evaluated 787 cognitively normal older individuals (65 years of age) with type 2 diabetes participating in the Israel Diabetes and Cognitive Decline study. Interactions in two-way analyses of covariance compared Group (Non-Ashkenazi versus Ashkenazi Jews) on the associations of Hp phenotype (Hp 1-1 versus non- Hp 1-1) with five cognitive outcome measures. The primary control variables were age, gender, and education.Compared with Ashkenazi Jews, non-Ashkenazi Jews with the Hp 1-1 phenotype had significantly poorer cognitive function than non-Hp 1-1 in the domains of Attention/Working Memory (p = 0.035) and Executive Function (p = 0.023), but not in Language/Semantic Categorization (p = 0.432), Episodic Memory (p = 0.268), or Overall Cognition (p = 0.082). After controlling for additional covariates (type 2 diabetes-related characteristics, cardiovascular risk factors, Mini-mental State Examination, and extent of depressive symptoms), Attention/Working Memory (p = 0.038) and Executive Function (p = 0.013) remained significant.Older individuals from specific ethnic/cultural backgrounds with the Hp 1-1 phenotype may benefit more from treatment targeted at decreasing or halting the detrimental effects of Hp 1-1 on the brain. Future studies should examine differential associations of Hp 1-1 and cognitive impairment, especially for groups with high prevalence of both, such as African-Americans and Hispanics.

To prospectively assess nonadherence to medications, the relationship between nonadherence and medical outcome and the relationship between a psychiatric risk factor (posttraumatic stress) and nonadherence in patients with a diagnosis of autoimmune hepatitis.Data were obtained in children with autoimmune hepatitis, who had consented to prospective monitoring of adherence, during 1 year of follow-up in our pediatric liver program. An electronic monitoring device as well as posttransplant trough blood levels of tacrolimus was used to evaluate adherence. A validated self-report questionnaire was used to assess posttraumatic stress. The medical outcome measure was the maximal alanine transaminase (ALT) for each monitored patient.Of 37 pediatric patients, 34 (15 posttransplant) enrolled. Fourteen (41%) used the monitoring device as directed. Monitor readings ranged between 28% and 94% of optimal adherence (100%). No patient took the medications exactly as prescribed. Electronic monitoring device readings correlated inversely with maximal ALT (P = 0.03, r = -0.59), and were also correlated with the tacrolimus level variability as a measure of adherence (P = 0.04, r = -0.72). Posttraumatic stress disorder questionnaire scores were correlated with both measures of adherence (for electronic monitoring, P = 0.02, r = -0.70, for tacrolimus levels, P = 0.03, r = 0.62).Nonadherence to immunosuppressants was common in this cohort, and it correlated with higher maximal ALT. Nonadherence is therefore an important risk factor for poor outcome in patients with autoimmune hepatitis. Posttraumatic stress symptoms, which were correlated with nonadherence, may serve as a focus for adherence-improving interventions.

Objective: To evaluate the performance of nondemented subjects 85 years and older on the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) neuropsychological battery, and to assess its relationship with sociodemographic variables. Methods: We studied 196 subjects enrolled in an Alzheimer’s Disease Research Center study who had a complete CERAD neuropsychological assessment. We used multiple regression analysis to predict performance on the neuropsychological tests from age, education, and sex. Eight representative hypothetical individuals were created (for example, an 87-year-old man, with high education). For each test, estimates of performance at the 10th, 25th, 50th, and 75th percentiles were reported for the eight representative hypothetical individuals. Results: Mean age was 89.2 years (SD = 3.2), mean years of education was 14.9 (SD = 3.2), and 66% of the sample were women. For 11 of the 14 neuropsychological tests, there was a significant multiple regression model using education, age, and sex as predictors. Neither the models nor the predictors used individually were significant for Delayed Recall, Savings, or correct Recognition. Among the significant results, seven had education as the strongest predictor. Lower age and higher education were associated with better performance. Women performed better than men in three of four tests with significant results for sex. Conclusions: In a sample of oldest old whose primary language is English, neuropsychological testing is influenced mainly by education and age. Cutoff scores based on younger populations and applied to the oldest old might lead to increased false-positive misclassifications.

Some, but not most, schizophrenia patients have below-average intelligence years before they manifest psychosis. However, it is not clear if those whose intelligence falls within-normal-range nevertheless have cognitive abnormalities. We examined the association between intra-individual variability in intellectual performance and risk for schizophrenia in individuals with normal IQ.555,326 adolescents, mandatory assessed by the Israeli Draft Board were followed up over 8 to 17 years for psychiatric hospitalization by means of the Israeli National Psychiatric Hospitalization Case Registry. Data were available on 4 intelligence sub-tests, and on behavioral and psychosocial variables. Variability was computed from the variance of the four intelligence tests' standardized scores.There was a significant monotonic association between increased intra-individual variability in intellectual performance and risk of schizophrenia in individuals with within-normal-range IQ. Individuals with the highest variability were 3.8 times more likely to have schizophrenia [95%CI: 2.32-6.08; p0.0001] compared with individuals with the lowest variability. This association held after controlling for the effects of potential confounders.Despite within-normal-range premorbid IQ, apparently healthy adolescents who will later on manifest schizophrenia, nevertheless have cognitive abnormalities such as increased variability across intellectual tasks, possibly related to frontal lobe abnormalities.

To test the utility of the UCLA posttraumatic stress disorder (PTSD) Index for DSM-IV (U-PTSD-I)(c) for predicting PTSD diagnosis in children with and without medical illnesses. The U-PTSD-I and a standard psychiatric interview were administered to medically ill children (n = 76) and children who experienced other traumatic events (n = 31). We found U-PTSD-I's sensitivity and specificity was better in the nonmedical illness cohort. Only intrusion symptoms were significantly associated with the diagnosis of PTSD in the medically ill. In conclusion, the U-PTSD-I performs better among general trauma versus medically ill patients. Intrusion symptoms should be focused on when assessing PTSD in medically ill children.

To examine the associations between postmortem Alzheimer disease (AD) neuropathology and autopsy-verified cardiovascular disease.The authors examined 99 subjects (mean age at death = 87.6; SD = 8.7) from the Mount Sinai School of Medicine Department of Psychiatry Brain Bank who were devoid of cerebrovascular disease-associated lesions or of non-AD-related neuropathology. Density of neuritic plaques (NPs) and neurofibrillary tangles (NFTs) as well as coronary artery and aortic atherosclerosis, left ventricular wall thickness, and heart weight were measured. Partial correlations were used to assess the associations of the four cardiovascular variables with NPs and NFTs in the hippocampus, entorhinal cortex, and multiple regions of the cerebral cortex after controlling for age at death, sex, dementia severity, body mass index, and ApoE genotype. These analyses were also repeated separately for ApoE4 carriers and noncarriers.The extent of coronary artery disease and to a lesser extent atherosclerosis were significantly associated with the density of cardinal neuropathologic lesions of AD in this autopsy sample (significant correlations between 0.22 and 0.29). These associations were more pronounced for the ApoE4 allele carriers (n = 42; significant correlations between 0.34 and 0.47).The degree of coronary artery disease is independently associated with the cardinal neuropathological lesions of Alzheimer disease. These associations are primarily attributable to individuals with the ApoE4 allele.

Microarray and other studies have reported oligodendrocyte and myelin-related (OMR) deficits in schizophrenia. Here, we employed a quantitative approach to determine the magnitude of OMR gene expression deficits and their brain-region specificity. In addition, we examined how expression levels among the studied OMR genes are interrelated. mRNA of MAG, CNP, SOX10, CLDN11, and PMP22, but not MBP and MOBP, was reduced in the hippocampus and anterior cingulate cortex but not in the putamen of patients with schizophrenia. Expression of the only protein examined (CNP) was decreased in the hippocampus but not in the putamen. Correlation and factor analyses revealed that mRNA levels for genes that did exhibit differential expression in schizophrenia (MAG, CNP, SOX10, CLDN11, and PMP2), as opposed to those that did not (MOBP and MBP), loaded on separate factors. Thus, OMR gene and protein expression deficits in schizophrenia are brain-region specific, and the affected components may share regulatory elements.

Objectives: This article assesses the impact of the attacks on 9/11 in New York City on drug use, relapse, and mental health from the perspective of drug users and patients in substance abuse treatment programs. Methods: Structured interviews were conducted with 16 administrators and 75 randomly selected patients at 15 substance abuse treatment programs in New York City from December 2002 to April 2003. Results: Drug use and relapse was a significant issue on and after 9/11. While Post Traumatic Stress Disorder was related to drug use, other preexisting mental health problems were not. Men were more likely to relapse than women; however, women were more emotionally affected by events following 9/11. Conclusions: The attacks on 9/11 may have contributed to relapse among drug users and exacerbated existing mental health problems among patients with a history of concurrent drug use and mental illness.

Objective. Exposure to emotionally traumatic events is common among children who are treated in pediatric medical care settings, and it is important to recognize the emotional reactions that children might develop as a response to the trauma. Practitioners sometimes rely on parental reports of the child's emotional reactions, but these reports may be biased by the parent's own posttraumatic symptoms. Understanding the differences between parent and child reports of the child's emotional symptoms is essential to guide proper diagnosis and care. This study evaluated discrepancies in parental versus child reports of the child's emotional trauma symptoms in pediatric medical care settings.Methods. We enrolled children and adolescents (age: 8–19) who had not previously received a diagnosis of a psychiatric disorder and were treated in pediatric specialty care clinics at Mount Sinai Medical Center in New York. We used the UCLA posttraumatic stress reaction index, child, adolescent, and parent versions, to evaluate child and parent reports of symptoms of posttraumatic stress disorder (PTSD) in the child. The Impact of Event Scale was used to evaluate the parents' own posttraumatic symptoms. We conducted a “best estimate” psychiatric diagnostic procedure to determine whether the child met diagnostic criteria for PTSD and evaluated the association between the diagnostic status (as determined by the “best estimate” procedure) and the results of the questionnaires.Results. A total of 115 patients and parents consented to the study, and 76 completed the evaluation. Sixty-four percent of the parents identified the child's traumatic experience as their own most traumatic experience, too. The child's self-report of PTSD symptoms was significantly correlated with the diagnosis of PTSD in the child. In contrast, parents' reports of their child's PTSD symptoms were not significantly associated with the child's diagnosis. Parents' own posttraumatic symptoms were associated with parental reports of the child's overall PTSD symptoms (correlation coefficient: 0.283).Conclusions. When a child is emotionally traumatized, the parent's own posttraumatic stress may influence his or her report and interpretation of the child's symptoms. Clinicians who evaluate children and adolescents for PTSD in medical care settings should directly seek the child's report and should not rely exclusively on parental reports. Parental reports of a child's PTSD symptoms can offer insights into the parent's own level of posttraumatic stress.

Background. In cross-sectional and longitudinal studies, type 2 diabetes has been positively associated with the risk of Alzheimer’s disease (AD). The present descriptive study compared diabetic and nondiabetic subjects on the severity of neuritic plaques and neurofibrillary tangles (NFTs) in the cerebral cortex and in the hippocampus. Methods. The study included specimens from 385 consecutive autopsies of residents of a nursing home (15.8% diabetics). Mean age at death ¼ 84 years [standard deviation (SD) ¼ 10], 66% were female, Clinical Dementia Rating mean ¼ 3.0 (SD ¼ 1.6), and 32.5% had an APOE4 allele. Additional analyses limited the sample to 268 subjects (14.1% diabetics) without neuropathology other than AD. Results. Analyses of covariance controlling for age at death, dementia severity (Clinical Dementia Rating score), and APOE4 allele indicated that diabetics had significantly fewer neuritic plaques (p ¼ .008) and NFTs (p ¼ .047) in the cerebral cortex than did nondiabetics. In the hippocampus, diabetics had significantly lower plaque ratings than did nondiabetics (p ¼ .019), but the lower ratings of NFTs did not achieve statistical significance (p ¼ .082). In the entire sample, diabetics had significantly less AD-associated neuropathology in all four analyses. Conclusions. These results raise the possibility that the varied associations observed between diabetes and AD may be specific to as yet ill-defined subgroups of dementia and diabetic patients or may be more characteristic of younger patients than of those who survive to a mean age of 84 years. Future studies are encouraged to examine a variety of other characteristics such as age that may interact with diabetes affecting the incidence of AD.

BACKGROUND: We conducted a 1-year follow-up of an original mail survey of early reactions to the World Trade Center disaster. METHOD: Of the 75 subjects originally surveyed, 58 (77%) responded. The survey included measures of dissociation (Dissociative Experiences Scale, Cambridge Depersonalization Scale, Clinician-Administered Dissociative States Scale), post-traumatic stress (Impact of Event Scale-Revised), social support (Interpersonal Support Evaluation List-short form), and a life quality measure (Quality of Life Enjoyment and Satisfaction Questionnaire-short form). We hypothesized that dissociative versus posttraumatic symptoms at follow-up could be dissected on the basis of early reactions. RESULTS: Responders and nonresponders did not differ in baseline characteristics. Exposure was not associated with dissociation or posttraumatic stress at follow-up. Of distress, dissociation, and posttraumatic stress at baseline, baseline dissociation was the strongest predictor of outcome dissociation while baseline posttraumatic stress was the strongest predictor of outcome posttraumatic stress. Of 4 peritraumatic distress factors generated in the original survey, "loss of control" and "guilt/shame" were significantly related to dissociation and posttraumatic stress at outcome, while "helplessness/anger" was only associated with posttraumatic stress at outcome. Lesser improvement in posttraumatic stress over the first year was significantly related to less social support and greater comorbid dissociation. Interim social support was associated with better life quality and fewer symptoms at outcome. CONCLUSION: There was evidence for partly independent pathways toward dissociation versus posttraumatic stress 1 year after the disaster. Feelings of guilt and shame, and persistent dissociation, were poor prognostic factors, while social support had a powerful ameliorating influence. Language: en

Objective Structural and functional brain reserves, thought to develop in childhood and adolescence, may be critical in determining the age at onset of cognitive impairment. Body height is affected by childhood conditions that promote growth. The authors examine the relationship of height in midlife and subsequent dementia, Alzheimer disease (AD), and vascular dementia. Methods Dementia was evaluated from 1999 to 2001 in 1,892 men age 76 to 95. Height had been measured when these men participated in the Israeli Ischemic Heart Disease project in 1963. Age, socioeconomic status (SES), and area of birth were also assessed in 1963. Results Older men and those with lower SES tended to be shorter. Relative to the shortest quartile, controlling for age, SES, and area of birth, the other quartiles had lesser respective odds ratios for dementia as a whole, AD, and vascular dementia. Conclusion Height was inversely associated with dementia, AD, and vascular dementia in a male sample. Since height is associated with childhood nutrition and may be associated with other risk factors for dementia, efforts to improve early life conditions that maximize body growth may diminish or delay the onset of dementia in later life.

BackgroundDespite anecdotal reports that serotonin reuptake inhibitors may improve depersonalisation, there is no proven efficacious treatment for depersonalisation disorder.AimsTo investigate the efficacy of fluoxetine in the treatment of depersonalisation disorder.MethodFifty-four people who met DSM-IV criteria for depersonalisation disorder were recruited through newspaper advertisements, and 50 were randomised to a 10-week, double-blind trial of fluoxetine 10–60 mg/day or placebo. Primary outcome measures were the Dissociative Experiences Scale-epersonalisation Factor, the Depersonalization Severity Scale and the Clinical Global Impression-Improvement (CGI-1) scale.ResultsIntention-to-treat analysis revealed that fluoxetine (mean dosage 48 mg/day) was not superior to placebo except for a clinically minimal but statistically significantly greater improvement in CGI-I score in the fluoxetine group prior to covarying for anxiety and depression (2.9 v. 3.6). Depersonalisation was significantly more likely to improve if comorbid anxiety disorder improved.ConclusionsFluoxetine was not efficacious in treating depersonalisation disorder, despite the commonly reported clinical use of serotonin reuptake inhibitors for this condition.

In contrast to the noradrenergic dysregulation described in PTSD, little is known regarding noradrenergic function in dissociative disorders. The purpose of this preliminary study was to investigate basal norepinephrine in depersonalization disorder (DPD). Nine subjects with DSM-IV DPD, without lifetime PTSD, were compared to nine healthy comparison (HC) subjects. Norepinephrine was measured via 24-h urine collection and three serial plasma determinations. Groups did not differ significantly in plasma norepinephrine levels. Compared to the HC group, the DPD group demonstrated significantly higher urinary norepinephrine, only prior to covarying for anxiety. The DPD group also demonstrated a highly significant inverse correlation between urinary norepinephrine and depersonalization severity (r=-0.88). Norepinephrine and cortisol levels (reported in a prior study) were not intercorrelated. We concluded that although dissociation accompanied by anxiety was associated with heightened noradrenergic tone, there was a marked basal norepinephrine decline with increasing severity of dissociation. The findings are in concordance with the few reports on autonomic blunting in dissociation and merit further investigation.