Genome-wide screen to identify genetic loci associated with cognitive decline in late-life depression.

OBJECTIVE: This study sought to conduct a comprehensive search for genetic risk of cognitive decline in the context of geriatric depression. DESIGN: A genome-wide association study (GWAS) analysis in the Neurocognitive Outcomes of Depression in the Elderly (NCODE) study. SETTING: Longitudinal, naturalistic follow-up study. PARTICIPANTS: Older depressed adults, both outpatients and inpatients, receiving care at an academic medical center. MEASUREMENTS: The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery was administered to the study participants at baseline and a minimum of twice within a subsequent 3-year period in order to measure cognitive decline. A GWAS analysis was conducted to identify genetic variation that is associated with baseline and change in the CERAD Total Score (CERAD-TS) in NCODE. RESULTS: The GWAS of baseline CERAD-TS revealed a significant association with an intergenic single-nucleotide polymorphism (SNP) on chromosome 6, rs17662598, that surpassed adjustment for multiple testing (p = 3.7 × 10-7; false discovery rate q = 0.0371). For each additional G allele, average baseline CERAD-TS decreased by 8.656 points. The most significant SNP that lies within a gene was rs11666579 in SLC27A1 (p = 1.1 × 10-5). Each additional copy of the G allele was associated with an average decrease of baseline CERAD-TS of 4.829 points. SLC27A1 is involved with processing docosahexaenoic acid (DHA), an endogenous neuroprotective compound in the brain. Decreased levels of DHA have been associated with the development of Alzheimer's disease. The most significant SNP associated with CERAD-TS decline over time was rs73240021 in GRXCR1 (p = 1.1 × 10-6), a gene previously linked with deafness. However, none of the associations within genes survived adjustment for multiple testing. CONCLUSIONS: Our GWAS of cognitive function and decline among individuals with late-life depression (LLD) has identified promising candidate genes that, upon replication in other cohorts of LLD, may be potential biomarkers for cognitive decline and suggests DHA supplementation as a possible therapy of interest.

Age, burnout and physical and psychological work ability among nurses.

Background: The ageing of the US labour force highlights the need to examine older adults' physical and psychological ability to work, under varying levels of occupational burnout. Aims: To examine how age and burnout interact in predicting physical and psychological work ability. Methods: Using a cohort of actively working nurses, we assessed factors on the Work Ability Index at 12-month follow-up and determined how these were related to age and exhaustion-related burnout at baseline. Results: The study group consisted of 402 nurses aged 25-67 (mean = 41.7). Results indicated age by burnout interactions in which decrements in physical work ability with greater age were observed at all but the lowest level of burnout (1.5 SD below mean: ß = -0.14, 95% CI -0.36, 0.07; 1 SD below: ß = -0.23, 95% CI -0.39, -0.06; mean: ß = -0.39, 95% CI -0.50, -0.29; 1 SD above: ß = -0.56, 95% CI -0.70, -0.42; 1.5 SD above: ß = -0.64, 95% CI -0.83, -0.46). In contrast, we observed decrements in psychological work ability with age at higher levels of burnout only (1 SD above: ß = -0.20, 95% CI -0.35, -0.05; 1.5 SD above: ß = -0.30, 95% CI -0.49, -0.11); at lower levels of burnout, older age was associated with improvements in this (1 SD below: ß = 0.19, 95% CI 0.03, 0.35; 1.5 SD below: ß = 0.29, 95% CI 0.08, 0.50). Conclusions: Findings indicated physical and psychological dimensions of work ability that differed by age and occupational burnout. This emphasizes the need for interventions to reduce burnout and to address age-related strengths and vulnerabilities relating to physical and psychological work ability.

Effects of early life stress on depression, cognitive performance and brain morphology.

BACKGROUND: Childhood early life stress (ELS) increases risk of adulthood major depressive disorder (MDD) and is associated with altered brain structure and function. It is unclear whether specific ELSs affect depression risk, cognitive function and brain structure. METHOD: This cross-sectional study included 64 antidepressant-free depressed and 65 never-depressed individuals. Both groups reported a range of ELSs on the Early Life Stress Questionnaire, completed neuropsychological testing and 3T magnetic resonance imaging (MRI). Neuropsychological testing assessed domains of episodic memory, working memory, processing speed and executive function. MRI measures included cortical thickness and regional gray matter volumes, with a priori focus on the cingulate cortex, orbitofrontal cortex (OFC), amygdala, caudate and hippocampus. RESULTS: Of 19 ELSs, only emotional abuse, sexual abuse and severe family conflict independently predicted adulthood MDD diagnosis. The effect of total ELS score differed between groups. Greater ELS exposure was associated with slower processing speed and smaller OFC volumes in depressed subjects, but faster speed and larger volumes in non-depressed subjects. In contrast, exposure to ELSs predictive of depression had similar effects in both diagnostic groups. Individuals reporting predictive ELSs exhibited poorer processing speed and working memory performance, smaller volumes of the lateral OFC and caudate, and decreased cortical thickness in multiple areas including the insula bilaterally. Predictive ELS exposure was also associated with smaller left hippocampal volume in depressed subjects. CONCLUSIONS: Findings suggest an association between childhood trauma exposure and adulthood cognitive function and brain structure. These relationships appear to differ between individuals who do and do not develop depression.

The COMT Val158Met polymorphism and cognition in depressed and nondepressed older adults.

OBJECTIVE: The objective of the current study was to examine the relationship between the COMT Val(158)Met polymorphism and neuropsychological performance in depressed and nondepressed older adults. METHODS: One hundred and twenty-six clinically depressed older adults and 105 nondepressed comparison participants were compared on neuropsychological performance and COMT Val(158)Met (Val/Val, Val/Met, Met/Met). RESULTS: Based on multivariate regression models, the COMT Val(158)Met polymorphism was not associated with cognitive performance among depressed or nondepressed individuals, nor did this polymorphism account for the fact that depressed individuals performed worse than nondepressed individuals on several neuropsychological tests that are typically affected by depression. There was also no difference in frequency of the COMT Val(158)Met alleles between depressed and nondepressed individuals. CONCLUSIONS: Although the current study found no association between COMT Val(158)Met polymorphism on a number of clinical neuropsychological tests that are typically found to be sensitive to depression, differential effects of the COMT Val(158)Met polymorphism on dopamine transmission in psychiatric and non-psychiatric populations may be further clarified by clinical research with neuroscience-based paradigms that segregate cognitive tasks into component processes with precise neural substrates, particularly with respect to the complex functions of the prefrontal cortex. Negative results can be important to narrowing down target processes and understanding the influence of clinical and demographic characteristics in studies of psychiatric genetics.

Neuropsychological correlates of magnetic resonance imaging-defined subcortical ischemic depression.

OBJECTIVE: The goal of the current study was to examine the neuropsychological profile of magnetic resonance imaging (MRI)-defined subcortical ischemic depression (SID). METHODS: Clinically depressed older adults with MRI-defined SID (n = 70) and depressed elders without SID (n = 75) were compared on neuropsychological performance, depression symptoms, and medical burden. RESULTS: Group comparisons revealed that the SID was associated with worse performance on all neuropsychological measures, but also with greater age, higher cardiac illness burden, and greater deficits in the depression symptoms of self-initiation and concentration. In multivariate regression models, auditory working memory and nonverbal memory remained worse among the SID group after controlling for contributions of age, cardiovascular risk, and depression symptoms. CONCLUSIONS: Although auditory working memory span and nonverbal memory appear to be specifically associated with the ischemic pathology that defines SID, the typical individual with SID is also likely to have a broader profile of neuropsychological deficits than those without SID because they are typically older and have specific depression symptoms that predispose them to compromised neurocognitive performance.

Prevalence of dementia in the United States: the aging, demographics, and memory study.

AIM: To estimate the prevalence of Alzheimer's disease (AD) and other dementias in the USA using a nationally representative sample. METHODS: The Aging, Demographics, and Memory Study sample was composed of 856 individuals aged 71 years and older from the nationally representative Health and Retirement Study (HRS) who were evaluated for dementia using a comprehensive in-home assessment. An expert consensus panel used this information to assign a diagnosis of normal cognition, cognitive impairment but not demented, or dementia (and dementia subtype). Using sampling weights derived from the HRS, we estimated the national prevalence of dementia, AD and vascular dementia by age and gender. RESULTS: The prevalence of dementia among individuals aged 71 and older was 13.9%, comprising about 3.4 million individuals in the USA in 2002. The corresponding values for AD were 9.7% and 2.4 million individuals. Dementia prevalence increased with age, from 5.0% of those aged 71-79 years to 37.4% of those aged 90 and older. CONCLUSIONS: Dementia prevalence estimates from this first nationally representative population-based study of dementia in the USA to include subjects from all regions of the country can provide essential information for effective planning for the impending healthcare needs of the large and increasing number of individuals at risk for dementia as our population ages.

Geriatric depression and cognitive impairment.

Cognitive impairment is common in geriatric depression, and depressed individuals with co-morbid cognitive impairment are at increased risk for a number of adverse medical, psychiatric and cognitive outcomes. This review focuses on clinical issues surrounding the co-occurrence of these two conditions within the context of current research. We (1) review the clinical criteria and prevalence of depression, as well as co-morbid cognitive impairment, (2) discuss factors associated with persistent cognitive impairment in depression, including dementia, and (3) review research relevant to the assessment and treatment of cognitive impairment and dementia in the context of depression. We conclude that current research on depression and cognition can inform clinical decisions that reduce the occurrence of adverse outcomes. Clinicians are encouraged to develop proactive approaches for treatment, which may include combinations of pharmacological and psychotherapeutic interventions.

Occupational characteristics and cognitive performance among elderly male twins.

OBJECTIVE: To examine the effect of occupational characteristics on cognitive status change in members of the NAS-NRC Twins Registry of World War II veterans. METHODS: Participants completed the modified Telephone Interview for Cognitive Status (TICS-m) on three occasions spanning a period of approximately 7 years. Based on factor analysis, occupational characteristics were interpreted as reflecting general intellectual demands (GI), human interaction and communication (HC), physical exertion (PE), and visual attention (VA). RESULTS: Based on regression analysis of TICS-m change that was dependent on twin pairing and additionally covarying for education, age at each testing event, medical conditions, and initial TICS-m score, higher GI was associated with a modest longitudinal improvement in TICS-m performance, whereas higher PE and VA were both associated with a modest decline. Subsequent analysis revealed that these significant effects were present among dizygotic twins, but not among monozygotic twins. CONCLUSIONS: Previous findings of a relationship between occupational characteristics and cognitive performance in later life may be partially explained by genetic factors; however, until these genes are identified, occupational characteristics may be useful markers.

Age effects of coronary artery bypass graft on cognitive status change among elderly male twins.

BACKGROUND: Research regarding long-term cognitive outcome following coronary artery bypass graft (CABG) is inconsistent, which may be due in part to differential genetic and environmental influences within most study samples. METHODS: The authors examined the effect of CABG on cognitive status change scores in members of the National Academy of Sciences-National Research Council Twins Registry of World War II veterans. Subjects were administered the modified Telephone Interview for Cognitive Status (TICS-m) at approximately 3-year intervals between 1990 and 2002 as part of an epidemiologic study of dementia. RESULTS: Based on co-twin control analyses using a repeated-measures analysis of variance matching twins discordant for CABG within the pair (n = 464 individuals) across three age categories (63 to 70, 71 to 73, 74 to 83), the authors found at follow-up that men who had CABG between ages 63 and 70 showed an increase in TICS-m scores and performed better than their co-twin who did not have the procedure. No significant differences were found within twin pairs for the older two age groups following CABG surgery. This age effect was replicated when comparing individuals positive for CABG surgery with nonfamilial, age- and education-matched controls who were negative for CABG. CONCLUSIONS: In this study of twin pairs who share many genetic and environmental risks for cerebrovascular problems, the results suggest that timing of the CABG procedure may be important to predicting positive cognitive outcomes.