The effect of multimorbidity on health related functioning: Temporary or persistent? Results from a longitudinal cohort study

ObjectiveMultimorbidity is known for its negative effects on health related functioning. It remains unclear if these effects are stable over time. The aim was to investigate if the relation between single morbidity/multimorbidity and health related functioning is temporary or persistent.MethodsData were collected as part of the Maastricht Aging Study (MAAS), a prospective study into the determinants of cognitive aging. Participants (n = 1184), 24–81 years old, were recruited from a patient database in primary care (Registration Network Family Practices). Morbidity status (i.e. healthy, single morbidity or multimorbidity) and the Short Form Health Survey (SF-36) were both assessed at baseline, at 3- and 6-year follow-up.ResultsAt baseline but not at 3- and 6-year follow-up, participants with single morbidity reported poorer physical functioning than their healthy counterparts. Multimorbidity was associated with poorer physical functioning at all measurements. Participants with multimorbidity showed a steep decrease in physical functioning between 3- and 6-year follow-up. Multimorbidity appeared to be unrelated to mental functioning. At baseline and at 3-year follow-up, participants who had a change in morbidity status reported poorer physical functioning than their healthy counterparts.ConclusionsPoorer physical functioning that accompanies multimorbidity is persistent and may even increase over time. People, who acquire one or more diseases during the 3-year follow-up, already showed poorer physical functioning at baseline compared to people who remained healthy during these years. Post-hoc analyses, using the SCL-90 as an outcome measure, did show that multimorbidity was related to depressive and anxiety complaints. However, these complaints seem to decline over time.     

Spouse's subjective social status predicts older adults’ prospective cognitive functioning

Objectives: The current study aims to investigate the association between subjective social status (SSS) and prospective cognitive functioning of older adults and their spouses, and to explore the potential mediating roles of health habits and physical activities in this association.

Method: Using the longitudinal data of 512 pairs of community-dwelling older couples aged 65–91 years (M = 72.2 ± 4.6), we tested the effects of SSS in cognitive functioning using an Actor-Partner Interdependence Model. SSS was measured by a self-anchoring social ladder, and cognitive functioning was measured by the Mini-Mental State Examination at baseline and 4-year follow-up. Socioeconomic status (i.e. education) was tested as a moderator, and physical activity (measured by the Physical Activity Scale for the Elderly) as well as health habits (i.e. tobacco and alcohol consumption) were included as potential mediators.

Results: A partner effect of SSS was found only in the low-education group, in which the wife's higher level of SSS in the community was associated with the husband's better cognitive functioning in the follow-up. A small proportion of this effect was found to be partially mediated by participation in housework, such that the wife's higher SSS was associated with the husband's increased housework activity, which was related to higher prospective cognitive functioning.

Conclusion: By examining the dyadic effects of SSS with a longitudinal design, our findings extended the understanding on how subjective social status influenced older couples’ cognitive health, and provided evidence-based insights for future studies on cognitive health in later life.     

Change in quality of life of medically hospitalized patients – A one-year follow-up study

Objectives: To examine changes in quality of life (QOL) among elderly medically hospitalized patients one year after hospitalization, and to explore factors associated with the changes.

Methods: A one-year follow-up study included 363 (175 men) medical inpatients with age range 65–98 (mean 80.2, SD 7.5) years. Information was collected at baseline and follow-up using the WHOQOL-BREF questionnaire assessing the physical, psychological, social and environment domain of QOL as the dependent variable, and the Mini-Mental State Examination, Lawton and Brody's scales for physical self-maintenance and instrumental activities of daily living, the Hospital Anxiety and Depression scale and assistance in living as the independent variables.

Results: The mean score of the physical domain of QOL had increased (mean change 0.6, SD 2.5; p?p? Conclusion: Good cognitive, physical and emotional health at baseline and follow-up were associated with improved QOL in previously hospitalized elderly patients independent of their need for assistance in living.     

Predictors of subjective age in people aged 40–79 years: a five-year follow-up study. The impact of mastery,mental and physical health

Objectives: Assessing subjective age perception (SAP) and changes in SAP as well as exploring which variables of socio-demographic, health and personal mastery independently predicted SAP.Methods: The panel data are from two waves of the Norwegian Study on the Life Course, Ageing and Generations (NorLAG). Our sample consists of 2471 people aged 40–79 years at baseline who were surveyed in 2002/2003 (T1) and 2007/2008 (T2). Univariate and multiple regressions were performed; multivariate analyses assessing the relative importance of the independent variables (at T1) for the SAP at T2.Results: Older chronological age, good physical health, good mental health, a high level of personal mastery and having lower education significantly predicted a youthful SAP. For the whole sample, older age and a high level of personal mastery were the most important predictors. For those aged 40–49 being a man, having lower education, good physical health and high personal mastery predicted a younger SAP, whereas in the group aged 50–59 years being married/cohabiting and having a high level of education were predictors of an older SAP. For those aged 60–69, high personal mastery was the only independent predictor of a younger SAP. For those aged 70–79 years, only health – good mental and physical health – independently predicted a younger SAP.Conclusions: Most respondents feel younger than their chronological age, the more the older they are. Self-rated physical and mental health and personal mastery are associated with SAP and vary in different age groups.     

Predictors of WAIS–R vocabulary in late life: Differences by race

Background: Vocabulary scores tend to be significantly related to education in heterogeneous groups of older adults, even after controlling for confounding variables. However, there may be other factors that impinge on cognitive functioning for certain demographic groups, particularly those whose educational opportunities were limited, and who may have experienced considerable stress as a result of their minority status. Objectives: This study sought to explore possible predictors of vocabulary scores among African American and White older adults. Method: In this study, samples of African American (N = 165) and White (N = 146) community-dwelling older adults reported their level of education, perceived health status, and number of stressful life events, and were administered the Wechsler Adult Intelligence Scale–Revised (WAIS–R) Vocabulary subtest. Results: Among the White participants, level of education was the only significant predictor of vocabulary score after controlling for perceived health and exposure to stress. Among African American participants, education was also a significant predictor of vocabulary score. However perceived health and number of stressful life events were also significantly predictors of vocabulary score. Conclusions: Findings indicate that for certain cohorts of older adults, especially those who may have experienced stressful life circumstances and health disparities as a result of racial inequality, education may not be the only variable that predicts verbal intelligence. The importance of investigating cognitive functioning within a broader sociocultural context is discussed.     

Moderate alcohol use and apolipoprotein E-4 (ApoE-4): Independent effects on cognitive outcomes in later life

Objectives: Substantive past research suggests that moderate alcohol use confers beneficial health outcomes. The study of moderate alcohol use and cognition has produced variable findings. The primary goal was to examine the relationship between alcohol use and cognitive aging over time (Experiment 1), in a demographically representative, longitudinal survey of older adults. Experiment 2 examined the hypothesis that apolipoprotein E-4 (ApoE-4) would moderate the relationship between moderate drinking and performance on cognitive domains.

Method: The sample was drawn from the Aging, Demographics, and Memory Study (ADAMS) supplement of the Health and Retirement Study (HRS) and included 856 participants over age 65 in 2001. Follow-up data were from 2002, 2006, and 2008. Alcohol use was measured via self-report. Control variables included gender, age, race, number of years of education, medical burden (total number of medical diseases), and marital status.

Results: Results of Experiment 1 indicated that moderate alcohol use was significantly associated with better baseline functioning across cognitive measures (p ≤ .05), but had no significant effect on rate of change over time across cognitive domains. Results of Experiment 2 indicated that while ApoE-4 carriage did not moderate the relationship between alcohol use and cognitive performance, generally, both ApoE-4 and moderate alcohol use were significant predictors of cognitive performance.

Conclusions: Overall, findings from this study support past findings that moderate alcohol use is associated with better cognitive functioning among community-dwelling older adults, and these relative benefits appear to persist throughout later life. However, the role of individual differences on manifestation of benefit remain very poorly understood. Future research should further examine the respective roles of demographic differences associated with cognitive aging, genetic moderators, and the influence of social interaction.     

Is improvement in impaired cognition and depressive symptoms in post‐stroke patients associated with recovery in activities of daily living?

Background and purpose – Depression and cognitive impairment after stroke are associated with physical functional outcomes, but there are limited data on whether depressive symptoms and cognitive status and improvements independently influence functional status and recovery. Methods – In a 6‐month prospective cohort study of 141 post‐acute stroke patients, demographic and clinical data on admission, and neurological, cognitive, depressive symptoms and functional variables on admission and at 6 months after stroke were measured using the National Institute of Health Stroke Scale (NIHSS), Abbreviated Mental Test (AMT), Geriatric Depression Scale (GDS) and Barthel Index (BI). Results – On multivariate analysis, severe activities of daily living (ADL) dependence at 6 months was significantly less likely associated with higher baseline AMT score denoting better cognitive status (OR = 0.68, 95% CI 0.48–0.97 per score point) and with greater AMT change score denoting greater cognitive improvement (OR = 0.61, 95% CI 0.41–0.91 per change score point); it was also more likely with higher baseline NIHSS scores denoting severe neurological impairment, (OR = 1.74, 95% CI 1.13–2.63 per point score), NIHSS change score [denoting lesser neurological improvement (OR = 1.83, 95% CI 1.13–2.93 per unit change score)], but was not associated with baseline or change scores of GDS. Greater magnitudes of functional recovery [BI change score (standardized beta)] were associated with better baseline depressive symptoms (?0.21) and improvement (?0.31), but not with cognitive status or improvement, in the presence of other significant variables, neurological status (?0.89) and improvement (?0.65), lower baseline physical functional status (?0.85) and younger age (?0.23). Conclusions – These data suggest that improving depressive symptoms in stroke patients may accelerate functional recovery, but the level of physical functioning achieved post‐stroke is determined by neurological and cognitive factors, consistent with the evidence that improvement of depressive symptoms through therapeutic intervention is limited by cognitive impairment.     

Does Low Subjective Social Status Predict Cognitive Decline in Chinese Older Adults? A 4-Year Longitudinal Study From Hong Kong

ObjectiveSubjective social status (SSS), one's self-perceived social position, encompasses not only concrete socio-economic (SES) factors (e.g., income) but also intangible aspects of status (e.g., social capital). In recent years, there has been increasing research interest in SSS as a predictor of a vast array of health outcomes but very few studies examining effects on cognitive functioning. This study's main objective was to examine the association between SSS and long-term cognitive decline in older Chinese adults.DesignA 4-year longitudinal study.SettingHong Kong, China.ParticipantsChinese adults (aged ≥65) (n = 3,153).MeasurementsThis study analyzed baseline SSS-Hong Kong (self-perceived social status within Hong Kong) and SSS-Community (self-perceived status within one's own social network) as predictors of long-term cognitive decline. Multiple-linear-regression was performed on 4-year follow-up Mini-Mental-Status-Examination (MMSE) cognitive function score (score range: 0–30) after adjusting for baseline MMSE scores, traditional SES indicators (e.g., education), demographic variables (e.g., sex), clinical conditions (e.g., stroke history, depression), and lifestyle variables (e.g., physical activity levels).ResultsLower SSS-Community but not SSS-Hong Kong was associated with greater cognitive decline (unstandardized coefficient (95% CI) = 0.13 (0.07, 0.19) standardized β-coefficient = 0.08, after adjusting for objective SES measures and other background and clinical factors. The standardized β-coefficients for the SSS-Community variable were similar in magnitude to those for depression and diabetes.ConclusionCognitive decline is influenced by self-perceived rank in proximal reference groups rather than socioeconomic comparison with society at-large. SSS-Community is a useful, single-item supplementary instrument to improve prediction of cognitive decline in elderly Chinese.     

Psychological well-being and metacognition in the fourth age: an explorative study in an Italian oldest old sample

Objectives: The research largely aimed at exploring the impact of marital status, cognitive efficiency, gender, physical health and sociocultural context on self-rated emotional competence, depression, memory and cognitive measures.Method: Ninety-four healthy adults aged 75–99 were recruited in the Sardinian province of Ogliastra, where a collectivistic culture prevails, and in northern Italy, which in turn is characterized by the prevalence of individualistic cultural traits. Participants were administered self-referent metacognitive efficiency, subjective wellness and depression measures.Results: Sardinian elders self-rated lower levels of depression and cognitive failures and had greater levels of emotional competence.Conclusions: Perceived psychological well-being, metacognitive efficiency and depression seem to be affected by sociocultural context.     

No cross-sectional evidence for an increased relation of cognitive and sensory abilities in old age1

Objectives: A key question in gerontological research concerns whether good functioning can be maintained in some cognitive abilities in old age, even if deficits occur in other cognitive or sensory abilities. Our goals were to investigate relations of cognitive and sensory abilities in old age, whether these relations differed in size across old age, and whether this was affected by general cognitive ability (processing speed), educational level, and/or general health status.

Methods: Two thousand eight hundred and twelve older adults (aged 65–101, M = 77.9 years) from the Vivre–Leben–Vivere survey served as cross-sectional sample for the present study. We administered psychometric tests on processing speed (the speed of cognitive processing), cognitive flexibility (the ability to alternate between cognitive operations), and verbal abilities (vocabulary). In addition, we interviewed individuals on their hearing, eyesight, educational level, and general health status. We regressed sizes of relations between abilities (calculated within each 1-year age tranche) on mean age within the corresponding age tranche, with the number of participants within the corresponding age tranche as case weights.

Results: We observed a decrease in relations between processing speed and cognitive flexibility in old age that was particularly pronounced in individuals with high educational level (r = ?.41). In contrast, we did not find differences in relations between other cognitive and sensory abilities across old age, which held for different levels of general cognitive ability, education, and general health status.

Conclusion: Present data do not support the view of a generally increased relation of cognitive and sensory abilities in old age.     

Selective attrition and intraindividual variability in response time moderate cognitive change

Objectives: Selection of a developmental time metric is useful for understanding causal processes that underlie aging-related cognitive change and for the identification of potential moderators of cognitive decline. Building on research suggesting that time to attrition is a metric sensitive to non-normative influences of aging (e.g., subclinical health conditions), we examined reason for attrition and intraindividual variability (IIV) in reaction time as predictors of cognitive performance. Method: Three hundred and four community dwelling older adults (64–92 years) completed annual assessments in a longitudinal study. IIV was calculated from baseline performance on reaction time tasks. Multilevel models were fit to examine patterns and predictors of cognitive change. Results: We show that time to attrition was associated with cognitive decline. Greater IIV was associated with declines on executive functioning and episodic memory measures. Attrition due to personal health reasons was also associated with decreased executive functioning compared to that of individuals who remained in the study. Discussion: These findings suggest that time to attrition is a useful metric for representing cognitive change, and reason for attrition and IIV are predictive of non-normative influences that may underlie instances of cognitive loss in older adults.     

Disruption of function: Neurophysiological markers of cognitive deficits in retired football players

ObjectiveRecent studies demonstrate that sports-related concussions can have negative consequences on long-term brain health. The goal of the present study was to determine whether retired Canadian Football League (CFL) athletes with a history of concussions exhibit alterations in neurocognitive functioning, along with changes in physical, social, and psychological health.MethodsOur study compared nineteen retired CFL athletes’ concussion histories to eighteen healthy age-matched controls with no history of concussion. Self-report inventories were used to assess depression, memory, attention, and general health. Neurophysiological markers of cognitive function were evaluated with event-related brain potentials (ERPs) as measured in two protocols: (1) A Mismatch Negativity (MMN) protocol for assessing the automatic early attentional brain mechanism; and, (2) a P300 auditory oddball task for assessing consciously controlled attention.ResultsRelative to controls, CFL players exhibited: response delays and reduced amplitudes in neurophysiological responses; overall decreases in cognitive function; and poorer scores on self-reports of physical, social, and psychological health; reflecting problems in all three categories.ConclusionOur findings demonstrate that multiple concussions sustained over several years can lead to altered cognitive and psychosocial function.SignificanceNeurophysiological markers of conscious and pre-conscious attention provide an objective assessment for evaluating long-term cognitive consequences of concussion.     

How neighborhoods and physical functioning are related: The roles of neighborhood socioeconomic status,perceived neighborhood strain,and individual health risk factors

Background: increasing attention is being paid to the impact of neighborhood residence on individual health status. Purpose: This study examined pathways through which low neighborhood socioeconomic status (SES) and associated subjective neighborhood characteristics may be associated with self-reported physical functioning.Methods: A sample of 658 adults responded to a questionnaire survey sent to residents of lower and higher SES neighborhoods. Measures of neighborhood social cohesion and problems were obtained and individual deprivation, social integration, sense of control, and financial strain were assessed with standard measures. Physical functioning was assessed with the MOS 36-item Short Form health survey.Results: Structural equation modeling analyses showed that living in a lower socioeconomic neighborhood was associated with greater perceived neighborhood strain, which, in turn, was associated with poorer physical functioning. Lower neighborhood SES and greater perceived neighborhood strain were associated with poorer physical functioning of individuals through less social integration, less perceived control, and greater financial strain. Individual deprivation was also related to less social integration, less perceived control, and greater financial strain.Conclusions: Neighborhood SES and associated perceptions of neighborhoods are associated with physical functioning to some extent through the shaping of the social and psychological experiences of individuals living within them. This research was supported by the Medical Research Council, UK.     

Reasons for living,meaning in life,and suicide ideation: investigating the roles of key positive psychological factors in reducing suicide risk in community-residing older adults

Objectives: To investigate the roles of reasons for living (RFL) and meaning in life (MIL) in potentially promoting mental health and well-being and protecting against suicide ideation among community-residing older adults and to investigate the psychometric properties of the Reasons for Living Scale-Older Adult version (RFL-OA).

Method: Of 173 older adults initially recruited into a longitudinal study on late-life suicide ideation, 109 completed the RFL-OA and measures of cognitive and physical functioning and positive and negative psychological factors at a two-year follow-up assessment. We tested a model in which RFL and MIL protect against suicide ideation, controlling for demographic and clinical factors. We also assessed the psychometric properties of the RFL-OA in community-residing older adults, investigating its internal consistency and its convergent (MIL, perceived social support, and life satisfaction), divergent (loneliness, depressive symptom severity, and suicide ideation), and discriminant validity (cognitive and physical functioning).

Results: RFL-OA scores explained significant variance in suicide ideation, controlling for age, sex, depressive symptom severity, and loneliness. MIL explained significant unique variance in suicide ideation, controlling for these factors and RFL, and MIL significantly mediated the association between RFL and suicide ideation. Psychometric analyses indicated strong internal consistency (α = .94), convergent, divergent, and discriminant validity for the RFL-OA relative to positive and negative psychological factors and cognitive and physical functioning.

Conclusion: These findings add to a growing body of literature suggesting merit in investigating positive psychological factors together with negative factors when assessing suicide risk and planning psychological services for older adults.     

The epidemiology of multiple somatic symptoms

BackgroundThe risk factors for a high total somatic symptom count are unclear; and it is not known whether total somatic symptoms count is a predictor of impaired health status.MethodA prospective population-based cohort study in North West England. Randomly sampled residents (1443 participants; 58% response) completed questionnaires to determine number of somatic symptoms (SSI), health status and a wide range of risk factors; 741 completed questionnaires 1 year later. We used logistic regression to identify risk factors for high SSI at follow-up and for persistently high SSI. We used ANCOVAR and multiple regression to assess whether baseline SSI predicted health status at follow-up.ResultsTwenty-one percent of participants scored over 25 on the Somatic Symptom Inventory (SSI) at baseline and 14% at both baseline and follow-up. Risk factors for a persistent high SSI were: fewer than 12 years of education, separated, widowed or divorced status, reported psychological abuse during childhood, co-existing medical illnesses, anxiety and depression. In multivariate analysis baseline SSI predicted health status (SF12 physical component score and health-related quality of life (EuroQol)) 12 months later. Persistent high SSI was a clinically meaningful predictor of these outcomes.ConclusionsOur data support a biopsychosocial approach to somatic symptoms rather than the dualistic approach of identifying “medically unexplained” symptoms. The risk factors for total somatic symptom count were those associated with psychiatric disorders including physical illness. A persistent high somatic symptom count provides a readily measured dimension of importance in epidemiology as a predictor of health status.     

Cognitive complaints after mild traumatic brain injury: Things are not always what they seem

ObjectiveTo compare nonreferred, emergency department (ED)-admitted mild traumatic brain injury (MTBI) patients with and without self-reported cognitive complaints on (1) demographic variables and injury characteristics; (2) neuropsychological test performance; (3) 12-day self-monitoring of perceived cognitive problems; and (4) emotional distress, physical functioning, and personality.Methods(Neuro)psychological assessment was carried out 6 months post-injury in 79 patients out of a cohort of 618 consecutive MTBI patients aged 18–60, who attended the ED of our level I trauma centre. Cognitive complaints were assessed with the Rivermead Postconcussional Symptoms Questionnaire (RPSQ). In addition, patients monitored concentration problems and forgetfulness during 12 consecutive days.ResultsSelf-reported cognitive complaints were reported by 39% of the patients. These complaints were strongly related to lower educational levels, emotional distress, personality, and poorer physical functioning (especially fatigue) but not to injury characteristics. Severity of self-reported cognitive complaints was neither associated with the patients' daily observations of cognitive problems nor with outcome on a range of neuropsychological tests.ConclusionSelf-reported cognitive complaints were more strongly related to premorbid traits and physical and emotional state factors than to actual cognitive impairments. In line with previous work, this suggests that treatment of emotional distress and fatigue may also reduce cognitive complaints. Cognitive outcome assessment of symptomatic MTBI patients should not be restricted to checklist ratings only, but also include a (neuro)psychological screening. In addition, daily monitoring of complaints is a useful method to gather information about the frequency and pattern of cognitive problems in daily life.     

Social participation predicts cognitive functioning in aging adults over time: comparisons with physical health,depression, and physical activity

Objectives: Several risk and protective factors are associated with changes in cognitive functioning in aging adults – including physical health, depression, physical activity, and social activities – though the findings for participation in social activities are mixed. This study investigated the longitudinal association between social participation and two domains of cognitive functioning, memory and executive function. A primary goal of our analyses was to determine whether social participation predicted cognitive functioning over-and-above physical health, depression, and physical activity in a sample with adequate power to detect unique effects.

Method: The sample included aging adults (N = 19,832) who participated in a large, multi-national study and provided data across six years; split into two random subsamples. Unique associations between the predictors of interest and cognitive functioning over time and within occasion were assessed in a latent curve growth model.

Results: Social participation predicted both domains of cognitive functioning at each occasion, and the relative magnitude of this effect was comparable to physical health, depression, and physical activity level. In addition, social participation at the first time point predicted change in cognitive functioning over time. The substantive results in the initial sample were replicated in the second independent subsample.

Conclusion: Overall, the magnitude of the association of social participation is comparable to other well-established predictors of cognitive functioning, providing evidence that social participation plays an important role in cognitive functioning and successful aging.     

Correlates of cognitive impairment in older Vietnamese

Objectives: This study examined correlates of cognitive functioning and possible cognitive impairment among older adults living in Da Nang, Vietnam and surrounding rural areas.

Methods: The analytic sample consisted of 489 adults, 55 and older stratified by gender, age, and residence in a rural or urban area. The sample was 46% rural, 44% women, with a mean age of 69.04. Interviews were conducted in individuals’ homes by trained interviewers. The dependent variable was a Vietnamese version of the mini mental status examination (MMSE). A multiple linear regression was run with the MMSE continuous scores reflecting cognitive functioning, while a binary logistic regression was conducted with an education-adjusted cut-off score reflecting possible cognitive impairment. Age, gender, education, material hardship, depressive symptoms Center for Epidemiologic Studies - Depression Scale, war injury, head trauma, diabetes, cardiovascular and cerebrovascular disease conditions served as correlates, controlling for marital status and rural/urban residence.

Results: About 33% of the sample scored below the standard cutoff of 23 on the MMSE. However, only 12.9% of the sample would be considered impaired using the education-adjusted cut-off score. Cognitive functioning and possible cognitive impairment as indicated by MMSE scores were significantly associated with being older, completing fewer years of education, and material hardship. Gender, depressive symptoms, and cerebrovascular disease were associated with cognitive functioning, but not cognitive impairment.

Conclusion: These results show that social characteristics, physical illness, and mental health are associated with cognitive functioning. The study also raises questions about the need for standardization of screening measures on Vietnamese populations.     

Depression and Cognitive Dysfunction in Older U.S. Military Veterans: Moderating Effects of BDNF Val66Met Polymorphism and Physical Exercise

ObjectiveDepression is associated with increased risk for cognitive dysfunction, yet little is known about genetic and behavioral factors that may moderate this association. Using data from a nationally representative sample of older U.S. military veterans, we examined the direct and interactive effects of depression, brain-derived neurotropic factor (BDNF) Val66Met genotype, and physical exercise on cognitive functioning.MethodsOne thousand three hundred eighty-six older European-American U.S. military veterans (mean age = 63) completed a web-based survey and cognitive assessment. Analyses of covariance were conducted to evaluate the effects of depression, BDNF Met allele carrier status, and physical exercise on these measures.ResultsDepressed veterans scored worse than nondepressed veterans on subjective measures of cognitive functioning (Cohen d's = 0.34–0.57) and objective measures of visual learning (d = 0.39) and working memory (d = 0.28). Among depressed veterans, those who were Met allele carriers scored worse than Val/Val homozygotes on subjective cognitive measures (d's = 0.52–0.97) and an objective measure of visual learning (d = 0.36). Engagement in physical exercise moderated the association between depression and cognitive function, with depressed exercisers scoring better than depressed nonexercisers on a subjective measure of reasoning, and objective measures of processing speed, attention, and visual learning (d = 0.58–0.99): further, in depressed Met allele carriers, exercisers scored better than nonexercisers on subjective cognitive (d's = 0.80–1.92), and objective measures of visual learning (d = 0.8–1.31) and working memory (d = 0.67).ConclusionDepression is associated with moderate decrements in cognitive functioning in older U.S. military veterans, and this association is moderated by BDNF Val66Met genotype and physical exercise. Prevention and treatment efforts designed to promote physical exercise may help preserve cognitive functioning in at-risk veterans.