Many studies have linked depression and obesity; few have more than two assessments of depressive symptoms and adiposity to address the potential bi-directional relation between adiposity and depressive symptoms from young adulthood through old age. We test whether baseline depressive symptoms are associated with changes in weight, whether baseline adiposity is associated with changes in depressive symptoms, and whether these associations vary by sex.
Participants (N=2,251; 47% female) were from the Baltimore Longitudinal Study of Aging. Using Hierarchical Linear Modeling on 30 years of data, the trajectory of adiposity and depressive symptoms over adulthood was estimated from >10,000 observations (M=4.5 assessments per participant) of body mass index (BMI; kg/m2), waist circumference, and hip circumference and >10,000 observations (M=4.5 assessments per participant) of the Center for Epidemiological Studies Depression scale. Baseline depressive symptoms and adiposity were then tested as predictors of the trajectory of adiposity and depressive symptoms, respectively. Additional analyses tested for sex-specific associations.
Sex moderated the association between depressive symptoms and weight gain such that women who experienced depressed affect had greater increases in BMI (binteraction=.12, SE=.04), waist (binteraction=.22, SE=.10) and hip circumference (binteraction=.20, SE=.07) across adulthood, controlling for relevant demographic and behavioral covariates. Baseline adiposity was unrelated to the trajectory of depressive symptoms (Median b=.00) for both sexes.
Women who experience symptoms of depression tend to gain more weight across adulthood than men who experience such symptoms. Whether an individual was normal weight or overweight was unrelated to changes in depressive symptoms across adulthood.
Although MRI detected white matter disease has been correlated with cognitive decline in the elderly, it is unclear whether white matter disease is primarily responsible for the cognitive deterioration or whether another process is common to white matter disease and dementia.
We examined the relationship between Alzheimer type brain pathology at autopsy and MRI detected cerebral white matter disease in 50 participants from the Baltimore Longitudinal Study of Aging (BLSA) Autopsy Program, a prospective study of aging which includes detailed cognitive assessments.
White matter disease was quantitated in pre- and postmortem MRI scans using the Cardiovascular Health Study (CHS) criteria in a blinded fashion. We found that several measures of Alzheimer disease (AD) pathology including CERAD score, Braak score and a composite AD pathology score, along with hypertension, were significantly associated with CHS white matter score using univariate and multivariate ordinal regression. In contrast, amyloid angiopathy was not independently related to with CHS score. While a clinical diagnosis of dementia was associated with CHS score in univariate analysis, the association disappeared after accounting for AD pathology.
Alzheimer’s pathology at autopsy is associated with MRI detected cerebral white matter disease. This relationship may explain, in part, the association between cerebral white matter disease and cognitive decline in the elderly.
Alzheimer’s; Dementia; MRI; White Matter Disease; Hypertension; Atherosclerosis
Reciprocal relations between weight and psychological factors suggest deep connections between mind and body. Personality traits are linked to weight gain; weight gain may likewise be associated with personality change. Using data from two diverse longitudinal samples (total N=1,919; 10 years average follow-up), we show that significant weight gain is associated with increases in both impulsiveness and deliberation: In both samples, middle-aged adults who gained ≥10% of their baseline body weight by follow-up increased in their tendency to give in to temptation, yet were more thoughtful about the consequences of their actions. The present research moves beyond life events to implicate health status in adult personality development. The findings also suggest that interventions that focus on the emotional component of impulse control may be more effective because even those who become more thoughtful about the consequences of their actions may have limited success at inhibiting their behavior.
Young to middle-aged women usually have notably lower rates of cardiovascular disease (CVD) than their male counterparts, but African American women lack this advantage. Their elevated CVD may be influenced by sex differences in associations between depressed mood and CVD risk factors. This cross-sectional study examined whether relations between scores on the Center for Epidemiologic Studies-Depression (CES-D) scale and a spectrum of CVD risk factors varied by sex among African Americans (n = 1076; ages 30–64) from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. Sex-stratified multiple regressions and logistic regressions were conducted. Among women, CES-D scores correlated positively with systolic blood pressure and waist-to-hip ratio (P's < .05), but inversely with high-density lipoprotein cholesterol (HDL-C) (P < .01). Women had twice the odds for metabolic syndrome if CES-D scores ≥16 and had a ≥14% increase in odds of hypertension, abdominal obesity, and low HDL-C with each 5-unit increase in CES-D scores. Among men, CES-D scores correlated positively with high-sensitivity C-reactive protein (P < .05), and odds of hypertension increased by 21% with each 5-unit increase in CES-D scores. Depressive symptoms may promote premature CVD risk in African Americans, at least in part, via CVD risk factors and prevalent metabolic syndrome, particularly in African American women.
To date, few systematic reviews of observational studies have been conducted to comprehensively evaluate the co-morbidity of IPV and specific depression outcomes in women. In this systematic review and meta-analysis, the authors summarized the extant literature and estimated the magnitude of the association between IPV and key depressive outcomes (elevated depressive symptoms, diagnosed major depressive disorder and postpartum depression). PubMed (January 1, 1980–Decemer 31, 2010) searches of English-language observational studies were conducted. Most of the selected 37 studies had cross-sectional population-based designs, focused on elevated depressive symptoms and were conducted in the United States. Most studies suggested moderate or strong positive associations between IPV and depression. Our meta-analysis suggested two to three-fold increased risk of major depressive disorder and 1.5 to 2-fold increased risk of elevated depressive symptoms and postpartum depression among women exposed to intimate partner violence relative to non-exposed women. A sizable proportion (9%–28%) of major depressive disorder, elevated depressive symptoms, and postpartum depression can be attributed to lifetime exposure to IPV. In an effort to reduce the burden of depression, continued research is recommended for evaluating IPV preventive strategies.
United States; Intimate partner violence; major depressive disorder; elevated depressive symptoms; postpartum depression; meta-analysis
The present research examines the effect of age, cohort, and time of measurement on well-being across adulthood. Cross-sectional and longitudinal analyses of two independent samples – one with >10,000 repeated assessments across 30 years (Assessments per participant: M =4.44, SD=3.47) and one with nationally representative data – suggested that well-being declines with age. This decline, however, reversed when we controlled for birth cohort. That is, once we accounted for the fact that older cohorts had lower levels of well-being, all cohorts increased in well-being with age relative to their own baseline. Participants tested more recently had higher well-being, but this time of measurement effect did not change the shape of the trajectory as did cohort. Although well-being increased with age for everyone, cohorts that lived through the economic challenges of the early 20th century had lower well-being than those born during more prosperous times.
Genome wide association studies have nominated many genetic variants for common human traits, including diseases, but in many cases the underlying biological reason for a trait association is unknown. Subsets of genetic polymorphisms show a statistical association with transcript expression levels, and have therefore been nominated as expression quantitative trait loci (eQTL). However, many tissue and cell types have specific gene expression patterns and so it is not clear how frequently eQTLs found in one tissue type will be replicated in others. In the present study we used two appropriately powered sample series to examine the genetic control of gene expression in blood and brain. We find that while many eQTLs associated with human traits are shared between these two tissues, there are also examples where blood and brain differ, either by restricted gene expression patterns in one tissue or because of differences in how genetic variants are associated with transcript levels. These observations suggest that design of eQTL mapping experiments should consider tissue of interest for the disease or other trait studied.
Previous studies showed that negative self-stereotypes detrimentally affect the
cognitive performance of marginalized group members; however, these findings were
confined to short-term experiments. In the present study, we considered whether
stereotypes predicted memory over time, which had not been previously examined. We also
considered whether self-relevance increased the influence of stereotypes on memory over
Multiple waves of memory performance were analyzed using individual growth models. The
sample consisted of 395 participants in the Baltimore Longitudinal Study of Aging.
Those with more negative age stereotypes demonstrated significantly worse memory
performance over 38 years than those with less negative age stereotypes, after adjusting
for relevant covariates. The decline in memory performance for those aged 60 and above
was 30.2% greater for the more negative age stereotype group than for the less negative
age stereotype group. Also, the impact of age stereotypes on memory was significantly
greater among those for whom the age stereotypes were self-relevant.
This study shows that the adverse influence of negative self-stereotypes on cognitive
performance is not limited to a short-term laboratory effect. Rather, the findings
demonstrate, for the first time, that stereotypes also predict memory performance over
an extended period in the community.
Ageism; Aging; Memory; Self-perception; Stereotypes
A chronically elevated white blood cell (WBC) count is a risk factor for morbidity and mortality. The present research tests whether facets of impulsivity – impulsiveness, excitement-seeking, self-discipline, and deliberation – are associated with chronically elevated WBC counts. Community-dwelling participants (N=5,652) from Sardinia, Italy, completed a standard personality questionnaire and provided blood samples concurrently and again three years later. Higher scores on impulsivity, in particular impulsiveness and excitement-seeking, were related to higher total WBC counts and higher lymphocyte counts at both time points. Impulsiveness was a predictor of chronic inflammation: For every standard deviation difference in this trait, there was an almost 25% higher risk of elevated WBC counts at both time points (OR=1.23, 95% CI=1.10–1.38). These associations were mediated, in part, by smoking and body mass index. The findings demonstrate that links between psychological processes and immunity are not limited to acute stressors; stable personality dispositions are associated with a chronic inflammatory state.
Personality; Impulsivity; White blood cells; Inflammation; Neuroticism; Conscientiousness
We examined longitudinal associations between ApoE4+ status and several cognitive outcomes and tested effect modification by sex. Data on 644 Non-Hispanic White adults, from the Baltimore Longitudinal Study of Aging (BLSA) were used. Dementia onset, cognitive impairment and decline were assessed longitudinally. After 27.5 years median follow-up, 113 participants developed dementia. ApoE4+ predicted dementia significantly (HR=2.89; 95% CI: 1.93–4.33), with non-significant sex differences. Taking all time points for predicting cognition, women had significantly stronger positive associations than men between ApoE4+ status and impairment or decline on the California Verbal Learning Test (CVLT-delayed recall and List A total recall) and on Verbal Fluency Test-Categories. This ApoE4×sex interaction remained significant with bonferroni correction only for CVLT-delayed recall. Taking time points prior to dementia for cognitive predictions, the positive association between impairment in CVLT-delayed recall and ApoE4+ status remained stronger among women, though only before bonferroni correction. While ApoE4+ status appears to be a sex neutral risk factor for dementia, its association with verbal memory and learning decline and impairment was stronger among women.
Apolipoprotein E genotype; dementia; cognitive decline; cognitive impairment; aging
Activity-dependent modulation of neuronal gene expression promotes neuronal survival and plasticity, and neuronal network activity is perturbed in aging and Alzheimer’s disease (AD). Here we show that cerebral cortical neurons respond to chronic suppression of excitability by downregulating the expression of genes and their encoded proteins involved in inhibitory transmission (GABAergic and somatostatin) and Ca2+ signaling; alterations in pathways involved in lipid metabolism and energy management are also features of silenced neuronal networks. A molecular fingerprint strikingly similar to that of diminished network activity occurs in the human brain during aging and in AD, and opposite changes occur in response to activation of N-methyl-D-aspartate (NMDA) and brain-derived neurotrophic factor (BDNF) receptors in cultured cortical neurons and in mice in response to an enriched environment or electroconvulsive shock. Our findings suggest that reduced inhibitory neurotransmission during aging and in AD may be the result of compensatory responses that, paradoxically, render the neurons vulnerable to Ca2+-mediated degeneration.
Alzheimer’s disease; Aging; GABA; Activity; Homeostatic disinhibition; Interneuron; Calcium; Synaptic scaling
The current study examined whether year-to-year variability in cognitive performance differ between individuals cognitively unimpaired and individuals who subsequently develop dementia.
Analyses included a case-control sample of Baltimore Longitudinal Study of Aging (BLSA; M age = 69.90, SD = 8.92) participants. One hundred and thirty five clinically diagnosed demented participants were matched with 135 non-demented participants based on age at initial testing and sex. Cognitive performance was examined using measures of memory, executive function, attention, language, and global mental status performance. Cognitive performance was examined from baseline to 5 years before cognitive impairment (mean assessments = 3.03, SD = 2.80).
Compared to unimpaired individuals, individuals diagnosed with dementia had greater variability on measures of attention, executive function, language, and semantic memory at least 5 years before the estimated onset of cognitive impairment, which may be indicative of maladaptive cognitive functioning. The dementia cases, however, had less variability on visual memory than the unimpaired group, which may suggest that these cases had more difficulty learning.
These results demonstrate that performance variability indexed over annual or biennial visits may be useful in identifying early signs of subsequent cognitive impairment.
Cognitive Impairment; Dementia; Neuropsychological tests; Cognition; Variability
Adiposity status and change are potential risk factors for Alzheimer's disease (AD). The authors used data on 2,322 participants in the Baltimore Longitudinal Study of Aging to analyze the relation between AD incidence and adiposity in Cox proportional hazards models, with adjustment for sociodemographic factors and smoking status. Body mass index (BMI; weight (kg)/height (m)2) and waist circumference at specific ages were predicted by empirical Bayes estimators from mixed-effects regression models. After a median of 23.4 years of follow-up between 1958 and 2006, 187 participants developed AD. Among men, being underweight (BMI ≤18.5) at age 30, 40, or 45 years increased the likelihood of AD (hazard ratio (HR) = 5.76, 95% confidence interval (CI): 2.07, 16.00); among women, being obese (BMI ≥30) at age 30, 40, or 45 years and jointly centrally obese (waist circumference ≥80th percentile) at age 30, 35, or 50 years increased AD risk (HR = 6.57, 95% CI: 1.96, 22.02). Women who lost weight (BMI change <10th percentile) between ages 30 and 45 years were also at increased risk (HR = 2.02, 95% CI: 1.06, 3.85). Weight gain among men (BMI change >90th percentile) between ages 30 and 50 years increased AD risk (HR = 3.70, 95% CI: 1.43, 9.56). Future studies should identify age- and gender-specific optimal weights and weight-loss strategies for preventing AD and investigate potential mechanisms.
adiposity; aging; Alzheimer disease; body mass index
Adiposity status and change are potential risk factors for Alzheimer’s disease (AD). The authors used data on 2,322 participants in the Baltimore Longitudinal Study of Aging to analyze the relation between AD incidence and adiposity in Cox proportional hazards models, with adjustment for sociodemographic factors and smoking status. Body mass index (BMI; weight (kg)/height (m)2) and waist circumference at specific ages were predicted by empirical Bayes estimators from mixed-effects regression models. After a median of 23.4 years of follow-up between 1958 and 2006, 187 participants developed AD. Among men, being underweight (BMI ≤ 18.5) at age 30, 40, or 45 years increased the likelihood of AD (hazard ratio (HR) = 5.76, 95% confidence interval (CI): 2.07, 16.00); among women, being obese (BMI ≥ 30) at age 30, 40, or 45 years and jointly centrally obese (waist circumference ≥ 80th percentile) at age 30, 35, or 50 years increased AD risk (HR = 6.57, 95% CI: 1.96, 22.02). Women who lost weight (BMI change <10th percentile) between ages 30 and 45 years were also at increased risk (HR = 2.02, 95% CI: 1.06, 3.85). Weight gain among men (BMI change >90th percentile) between ages 30 and 50 years increased AD risk (HR = 3.70, 95% CI: 1.43, 9.56). Future studies should identify age- and gender-specific optimal weights and weight-loss strategies for preventing AD and investigate potential mechanisms.
adiposity; aging; Alzheimer disease; body mass index
Statin use and serum cholesterol reduction have been proposed as preventions for dementia and mild cognitive impairment (MCI).
1,604 and 1,345 eligible participants from the Baltimore Longitudinal Study of Aging (BLSA) were followed after age 50 for a median time of around 25 years, to examine incidence of dementia (n=259) and MCI (n=138), respectively. Statin use (ever-use and time-dependent use), total cholesterol levels (TC; first-visit and time-dependent), TC change trajectory from first-visit, and high-density lipoprotein (HDL-C):TC ratio (first-visit and time-dependent) were main exposures of interest. Cox proportional hazards models were used.
Participants with incident dementia had higher first-visit TC compared to participants who remained free of dementia and MCI, while first-visit TC was higher among statin ever-users compared to never-users (age-unadjusted associations). Statin users had two to three-fold lower risk of developing dementia (HR=0.41; 95% CI: 0.18–0.92), but not MCI, when considering time-dependent “statin use” with propensity score model adjustment. This association remained significant independently of serum cholesterol exposures. An elevated first-visit TC was associated with reduced MCI risk (Upper quartile (Q4) vs. Q1: HR=0.51; 95% CI=0.29–0.90). Compared to the lowest quartile (Q1: 0.00–0.19), HDL-C:TC (time-dependent) in (Q2: 0.19–0.24) was associated with reduced MCI risk (HR=0.53; 95%CI: 0.30–0.94). Among men only, TC decline from first-visit was significantly associated with increased dementia risk (HR=4.21; 95% CI: 1.28–13.85).
Statins may have multifactorial effects on dementia but not MCI risk. Future interventions may be warranted and research should focus on optimal serum TC, HDL-C:TC ratio and TC change trajectories.
Statins; serum cholesterol; dementia; mild cognitive impairment; aging
To determine the relationship between hearing loss and cognitive function as assessed with a standardized neurocognitive battery. We hypothesized a priori that greater hearing loss is associated with lower cognitive test scores on tests of memory and executive function.
A cross-sectional cohort of 347 participants ≥ 55 years in the BLSA without mild cognitive impairment or dementia had audiometric and cognitive testing performed in 1990–1994. Hearing loss was defined by an average of hearing thresholds at 0.5, 1, 2, and 4 kHz in the better-hearing ear. Cognitive testing consisted of a standardized neurocognitive battery incorporating tests of mental status, memory, executive function, processing speed, and verbal function. Regression models were used to examine the association between hearing loss and cognition while adjusting for confounders.
Greater hearing loss was significantly associated with lower scores on measures of mental status (Mini-Mental State Exam), memory (Free Recall), and executive function (Stroop Mixed, Trail Making B). These results were robust to analyses accounting for potential confounders, non-linear effects of age, and exclusion of individuals with severe hearing loss. The reduction in cognitive performance associated with a 25 dB hearing loss was equivalent to the reduction associated with an age difference of 6.8 years.
Hearing loss is independently associated with lower scores on tests of memory and executive function. Further research examining the longitudinal association of hearing loss with cognitive functioning is needed to confirm these cross-sectional findings.
Hearing loss; cognition; aging; dementia
Persons with elevated blood pressure show dampened emotional responses to affect-laden stimuli. We sought to further examine cardiovascular emotional dampening by examination of the relationship between resting hemodynamic measures and recognition of emotion in an African-American community-based sample.
Participants were 106 African American men and women (55 female; mean age 52.8 years), mainly low in socioeconomic status and part of the Healthy Aging in Nationally Diverse Longitudinal Samples (HANDLS-Pilot) Pilot Study. Participants evaluated emotional expressions in faces and in sentences using the Perception of Affect Test (PAT). Resting blood pressure, total peripheral resistance (TPR), cardiac output and heart rate were obtained continuously using a Portapres blood pressure monitor.
Total PAT scores were inversely related to systolic (r = −.30) and diastolic (r = −.24) blood pressure, TPR (r = −.36) and age (r = − .31; p values < .01), and positively related to cardiac output (r = .27) and education (r = .38; p values <.01), and with mental state (r = .25) and body mass index (r = −.20; p values < .05). Accuracy of emotion recognition on the PAT tasks remained inversely related to TPR and blood pressure after adjustment for demographic variables, medication, mental state and body mass index.
Elevated blood pressure and TPR were associated with reduced perception of affect. TPR was the most consistent independent hemodynamic correlate of emotional dampening for the PAT scores. These results suggest potentially important links among CNS regulation of emotions, hemodynamic processes and hypertension development.
Emotion regulation; blood pressure; hemodynamics; hypertension development; central nervous system; stress
The present study examined the association of serum ferritin with CHD risk using the Framingham Heart Study's 10-year risk algorithm.
Ordinal logistic regression modelling was used to interpret risk. Proportional odds modelling assessed four divisions of ranked CHD risk (4, high; 3, increased; 2, slight; 1, minimal), separately by sex.
Baltimore, MD, USA.
African-American and white participants (n 1823) from baseline of the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study, aged 30–64 years.
For men, there was a 0.5% increase in risk for every 10-unit rise in serum ferritin (pmol/l). Other significant predictors included increased BMI, white race, unemployment and C-reactive protein ≥9.5 mg/l. For women, there was a 5.1% increase in risk per 10-unit rise in serum ferritin (pmol/l). Other significant predictors included increased BMI, lower education, unemployment and C-reactive protein ≥9.5 mg/l.
Serum ferritin is a significant predictor of 10-year hard CHD risk for HANDLS study participants, a low-income, urban population. Serum ferritin, independent of elevated C-reactive protein, was associated with increased 10-year CHD risk for HANDLS participants. To our knowledge, these data provide the first evidence of the role of serum ferritin as a risk factor for hard CHD in African-American and white postmenopausal women in the USA. Future research on cardiovascular events from this prospective study may confirm the association.
CVD; Cohort study; Serum ferritin; CHD; Iron
Serum urate concentrations are highly heritable and elevated serum urate is a key risk factor for gout. Genome-wide association studies (GWAS) of serum urate in African American (AA) populations are lacking. We conducted a meta-analysis of GWAS of serum urate levels and gout among 5820 AA and a large candidate gene study among 6890 AA and 21 708 participants of European ancestry (EA) within the Candidate Gene Association Resource Consortium. Findings were tested for replication among 1996 independent AA individuals, and evaluated for their association among 28 283 EA participants of the CHARGE Consortium. Functional studies were conducted using 14C-urate transport assays in mammalian Chinese hamster ovary cells. In the discovery GWAS of serum urate, three loci achieved genome-wide significance (P< 5.0 × 10−8): a novel locus near SGK1/SLC2A12 on chromosome 6 (rs9321453, P= 1.0 × 10−9), and two loci previously identified in EA participants, SLC2A9 (P= 3.8 × 10−32) and SLC22A12 (P= 2.1 × 10−10). A novel rare non-synonymous variant of large effect size in SLC22A12, rs12800450 (minor allele frequency 0.01, G65W), was identified and replicated (beta −1.19 mg/dl, P= 2.7 × 10−16). 14C-urate transport assays showed reduced urate transport for the G65W URAT1 mutant. Finally, in analyses of 11 loci previously associated with serum urate in EA individuals, 10 of 11 lead single-nucleotide polymorphisms showed direction-consistent association with urate among AA. In summary, we identified and replicated one novel locus in association with serum urate levels and experimentally characterize the novel G65W variant in URAT1 as a functional allele. Our data support the importance of multi-ethnic GWAS in the identification of novel risk loci as well as functional variants.
Personality traits contribute to health outcomes, in part through their association with major controllable risk factors, such as obesity. Body weight, in turn, reflects our behaviors and lifestyle and contributes to the way we perceive ourselves and others. In this study, we use data from a large (N=1,988) longitudinal study that spanned more than 50 years to examine how personality traits are associated with multiple measures of adiposity and with fluctuations in body mass index (BMI). Using 14,531 anthropometric assessments, we modeled the trajectory of BMI across adulthood and tested whether personality predicted its rate of change. Measured concurrently, participants higher on Neuroticism or Extraversion or lower on Conscientiousness had higher BMI; these associations replicated across body fat, waist, and hip circumference. The strongest association was found for the impulsivity facet: Participants who scored in the top 10% of impulsivity weighed, on average, 11Kg more than those in the bottom 10%. Longitudinally, high Neuroticism and low Conscientiousness, and the facets of these traits related to difficulty with impulse control, were associated with weight fluctuations, measured as the variability in weight over time. Finally, low Agreeableness and impulsivity-related traits predicted a greater increase in BMI across the adult lifespan. BMI was mostly unrelated to change in personality traits. Personality traits are defined by cognitive, emotional, and behavioral patterns that likely contribute to unhealthy weight and difficulties with weight management. Such associations may elucidate the role of personality traits in disease progression and may help to design more effective interventions.
The Baltimore Longitudinal Study of Aging (BLSA) was established in 1958 and is one the oldest prospective studies of aging in the USA and the world. The BLSA is supported by the National Institute of Aging (NIA) and its mission is to learn what happens to people as they get old and how to sort out changes due to aging and from those due to disease or other causes. In 1986, an autopsy program combined with comprehensive neurologic and cognitive evaluations was established in collaboration with the Johns Hopkins University Alzheimer’s Disease Research Center (ADRC). Since then, 211 subjects have undergone autopsy. Here we review the key clinical neuropathological correlations from this autopsy series. The focus is on the morphological and biochemical changes that occur in normal aging, and the early neuropathological changes of neurodegenerative diseases, especially Alzheimer’s disease (AD). We highlight the combined clinical, pathologic, morphometric, and biochemical evidence of asymptomatic AD, a state characterized by normal clinical evaluations in subjects with abundant AD pathology. We conclude that in some individuals, successful cognitive aging results from compensatory mechanisms that occur at the neuronal level (i.e., neuronal hypertrophy and synaptic plasticity) whereas a failure of compensation may culminate in disease.
α-synuclein; Alzheimer’s disease; asymptomatic Alzheimer’s disease; amyloid-β; dementia; Parkinson’s disease; stereology; successful aging; tau
Previous studies indicate a high risk of Posttraumatic Stress Disorder (PTSD) among women and low-income, urban-residing African Americans. This study examined PTSD symptoms among urban-residing, socioeconomically diverse, working age, African Americans and whites. Participants completed the PTSD Checklist-Civilian Version. Of the 2,104 participants, 268 (12.7%) screened positive for PTSD symptoms. Women (13.8%) were more likely than men (11.3%), white participants (13.8%) were more likely than African Americans (11.9%), and younger participants (16.1%) were more likely than older (10.2%) to screen positive for PTSD symptoms. A significant interaction (p = .05) revealed that white women living below the 125% poverty level were most likely to report PTSD symptoms. These findings highlight the importance of PTSD screening in low-income, urban neighborhoods.
Symptoms of Posstraumatic Stress Disorder; civilians; urban residents
Genome-wide association studies have nominated many genetic variants for common human traits, including diseases, but in many cases the underlying biological reason for a trait association is unknown. Subsets of genetic polymorphisms show a statistical association with transcript expression levels, and have therefore been nominated as expression quantitative trait loci (eQTL). However, many tissue and cell types have specific gene expression patterns and so it is not clear how frequently eQTLs found in one tissue type will be replicated in others. In the present study we used two appropriately powered sample series to examine the genetic control of gene expression in blood and brain. We find that while many eQTLs associated with human traits are shared between these two tissues, there are also examples where blood and brain differ, either by restricted gene expression patterns in one tissue or because of differences in how genetic variants are associated with transcript levels. These observations suggest that design of eQTL mapping experiments should consider tissue of interest for the disease or other traits studied.
► We integrate GWAS SNPs and examine the genetic control of gene expression in blood and brain tissue. ► Many eQTLs associated with human traits are shared between the blood and the brain. ► A number of discrete, tissue specific eQTLs also exist in the blood or the brain. ► Functional studies in blood have a limited capacity to inform on regulatory variation in the brain. ► Design of eQTL mapping experiments should consider the tissue of interest for the phenotype studied.
eQTL; GWAS; Brain; Blood
Animal models and clinical studies suggest that brain-derived neurotrophic factor (BDNF) is involved in the pathophysiology of depression. We test whether serum and plasma levels of BDNF are associated with trait Neuroticism and its facets, and with state measure of depressive symptoms.
In a community-based cohort (N = 2099) we measured serum and plasma BDNF concentration, administered the Revised NEO Personality Inventory (NEO-PI-R) and the Center for Epidemiologic Studies Depression Scale (CES-D). Covariates included age, sex, cigarette smoking, obesity, and antidepressant use.
Serum BDNF concentrations were inversely related to Neuroticism (r = −0.074, P < 0.001), in particular the Depression facet (r = −0.08, P < 0.001). Lower BDNF concentrations were also associated with severe depressive symptoms (CES-D ≥ 28; OR = 0.906; 95%CI = 0.851–0.965). The association of serum BDNF with Neuroticism was independent of depressive symptoms, indicating that serum BDNF might represent a biological correlate of Neuroticism and not just of transient depressive states. Plasma BDNF was not associated with measures of depression.
Our study suggests that lower serum BDNF is associated with both a dispositional vulnerability to depression and acute depressive states in the general population.
neuroticism; depression; brain-derived neurotrophic factor (BDNF); serum; plasma
In a community-dwelling sample (N=4,790; age range 14–94), we examined whether personality traits prospectively predicted performance on a verbal fluency task. Open, extraverted, and emotionally stable participants had better verbal fluency. At the facet level, dispositionally happy and self-disciplined participants retrieved more words; those prone to anxiety and depression and those who were deliberative retrieved fewer words. Education moderated the association between Conscientiousness and fluency such that participants with lower education performed better on the fluency task if they were also conscientious. Age was not a moderator at the domain level, indicating that the personality-fluency associations were consistent across the lifespan. A disposition towards emotional vulnerability and being less open, less happy, and undisciplined may be detrimental to cognitive performance.
Verbal fluency; Personality; Five-Factor Model; Semantic fluency