Cognitive performance in antidepressant-free recurrent major depressive disorder.

BACKGROUND: Cognitive complaints are common in depression, and cognition may be an important treatment target as cognitive problems often remain during remission and may contribute to recurrence risk. Previous studies of cognitive performance in depression have mainly examined late-life depression, with a focus on older adults, or assessed performance in specific cognitive tasks rather than cognitive domains. METHODS: This study examined cognitive performance across multiple cognitive domains in antidepressant-free depressed adults with early onset recurrent depression compared to never-depressed controls. Domain scores were calculated for episodic memory, executive function, processing speed, and working memory, and the effect of depression diagnosis, depression severity, and depression duration on each domain score was examined, including interactions with age, sex, and education. RESULTS: Currently depressed adults (n = 91) exhibited poorer performance in the processing speed domain compared with never-depressed adults (n = 105). Additionally, there was an interactive effect of depression duration and age on processing speed and executive function domain performance, such that performance was worse with older age and longer duration of depression. There were no effects of depression severity on performance across the cognitive domains. CONCLUSIONS: These findings support that processing speed deficits appear in young adults with early onset depression that may not be related to current mood. Additionally, the effects of cumulative depressive episodes may interact with aging such that cognitive performance deficits worsen with recurrence over the lifespan.

Predictors of recurrence in remitted late-life depression.

BACKGROUND: Late-life depression (LLD) is associated with a fragile antidepressant response and high recurrence risk. This study examined what measures predict recurrence in remitted LLD. METHODS: Individuals of age 60 years or older with a Diagnostic and Statistical Manual - IV (DSM-IV) diagnosis of major depressive disorder were enrolled in the neurocognitive outcomes of depression in the elderly study. Participants received manualized antidepressant treatment and were followed longitudinally for an average of 5 years. Study analyses included participants who remitted. Measures included demographic and clinical measures, medical comorbidity, disability, life stress, social support, and neuropsychological testing. A subset underwent structural magnetic resonance imaging (MRI). RESULTS: Of 241 remitted elders, approximately over 4 years, 137 (56.8%) experienced recurrence and 104 (43.2%) maintained remission. In the final model, greater recurrence risk was associated with female sex (hazard ratio [HR] = 1.536; confidence interval [CI] = 1.027-2.297), younger age of onset (HR = 0.990; CI = 0.981-0.999), higher perceived stress (HR = 1.121; CI = 1.022-1.229), disability (HR = 1.060; CI = 1.005-1.119), and less support with activities (HR = 0.885; CI = 0.812-0.963). Recurrence risk was also associated with higher Montgomery-Asberg Depression Rating Scale (MADRS) scores prior to censoring (HR = 1.081; CI = 1.033-1.131) and baseline symptoms of suicidal thoughts by MADRS (HR = 1.175; CI = 1.002-1.377) and sadness by Center for Epidemiologic Studies-Depression (HR = 1.302; CI, 1.080-1.569). Sex, age of onset, and suicidal thoughts were no longer associated with recurrence in a model incorporating report of multiple prior episodes (HR = 2.107; CI = 1.252-3.548). Neither neuropsychological test performance nor MRI measures of aging pathology were associated with recurrence. CONCLUSIONS: Over half of the depressed elders who remitted experienced recurrence, mostly within 2 years. Multiple clinical and environmental measures predict recurrence risk. Work is needed to develop instruments that stratify risk.

Longitudinal Cognitive Outcomes of Clinical Phenotypes of Late-Life Depression.

OBJECTIVE: Late-life depression is associated with cognitive deficits and increased risk for cognitive decline. The purpose of the study was to determine whether clinical characteristics could serve as phenotypes informative of subsequent cognitive decline. Age at depression onset and antidepressant remission at 3 months (acute response) and 12 months (chronic response) were examined. METHODS: In a longitudinal study of late-life depression in an academic center, 273 depressed and 164 never-depressed community-dwelling elders aged 60 years or older were followed on average for over 5 years. Participants completed annual neuropsychological testing. Neuropsychological measures were converted to z-scores derived from the baseline performance of all participants. Cognitive domain scores at each time were then created by averaging z-scores across tests, grouped into domains of episodic memory, attention-working memory, verbal fluency, and executive function. RESULTS: Depressed participants exhibited poorer performance at baseline and greater subsequent decline in all domains. Early-onset depressed individuals exhibited a greater decline in all domains than late-onset or nondepressed groups. For remission, remitters and nonremitters at both 3 and 12 month exhibited greater decline in episodic memory and attention-working memory than nondepressed subjects. Three-month remitters also exhibited a greater decline in verbal fluency and executive function, whereas 12-month nonremitters exhibited greater decline in executive function than other groups. CONCLUSION: Consistent with past studies, depressed elders exhibit greater cognitive decline than nondepressed subjects, particularly individuals with early depression onset, supporting the theory that repeated depressive episodes may contribute to decline. Clinical remission is not associated with less cognitive decline.

Effects of stressful life events on cerebral white matter hyperintensity progression.

OBJECTIVE: Exposure to stressful events is associated with both occurrence of depression and also vascular disease. The objective of this study was to determine whether higher levels of stress exposure was related to measures of pathological brain aging, specifically white matter hyperintensity volumes, in older adults with and without depression. METHODS: The sample included 130 depressed and 110 never-depressed older adults aged 60 years or older enrolled in a longitudinal study at an academic medical center. Participants completed clinical assessments, assessment of stressful event exposure and perceived stress, and magnetic resonance imaging at baseline and after 2 years. Analyses examined both cross-sectional and longitudinal relationships between stress measures and white matter hyperintensity volumes. RESULTS: There were no statistically significant relationships observed between cross-sectional baseline stress measures and either baseline hyperintensity volume or 2-year change in hyperintensity volume. However, after controlling for demographic variables and baseline measures, change in stressor exposure was associated with change in hyperintensity volumes. In this analysis, increased stressor exposure was associated with greater increases in white matter hyperintensity volume, while reductions in stressor exposure were associated with less increase in hyperintensity volume. This relationship did not significantly differ based on the presence of either depression or medical comorbidities. CONCLUSIONS: This work adds to a growing literature associating exposure to stressful events in later life with more rapid pathological brain aging. Work is needed to understand the physiological mechanisms by which stress exposure has this effect and examine whether stress reduction techniques may modify these observed outcomes. Copyright © 2016 John Wiley & Sons, Ltd.

Physical frailty in late-life depression is associated with deficits in speed-dependent executive functions.

OBJECTIVE: The aim of this study was to examine the association between physical frailty and neurocognitive performance in late-life depression (LLD). METHODS: Cross-sectional design using baseline data from a treatment study of late-life depression was used in this study. Individuals aged 60 years and older were diagnosed with major depressive disorder at time of assessment (N = 173). All participants received clinical assessment of depression and completed neuropsychological testing during a depressive episode. Physical frailty was assessed using an adaptation of the FRAIL scale. Neuropsychological domains were derived from a factor analysis that yielded three factors: (i) speeded executive and fluency, (ii) episodic memory, and (iii) working memory. Associations were examined with bivariate tests and multivariate models. RESULTS: Depressed individuals with a FRAIL score >1 had worse performance than nonfrail depressed across all three factors; however, speeded executive and fluency was the only factor that remained significant after controlling for depression symptom severity and demographic characteristics. CONCLUSIONS: Although physical frailty is associated with broad neurocognitive deficits in LLD, it is most robustly associated with deficits in speeded executive functions and verbal fluency. Causal inferences are limited by the cross-sectional design, and future research would benefit from a comparison group of nondepressed older adults with similar levels of frailty. Research is needed to understand the mechanisms underlying associations among depression symptoms, physical frailty, and executive dysfunction and how they are related to the cognitive and symptomatic course of LLD.

Appetite loss and neurocognitive deficits in late-life depression.

OBJECTIVES: This study aimed to examine the association of appetite loss symptoms to neurocognitive performance in late-life depression (LLD). METHODS: This study used cross-sectional data from individuals aged 60+ years with major depressive disorder (N = 322). Participants received clinical assessment of depression and neuropsychological testing. Factor analysis was used to characterize depression symptom factors, and composite scales were developed for episodic memory, psychomotor-executive functions, verbal fluency, and working memory span. RESULTS: Factor analysis produced a five-factor solution: (1) anhedonia/sadness; (2) suicidality/guilt; (3) appetite/weight loss; (4) sleep disturbance; and (5) anxiety/tension. In separate multivariate models for each neurocognitive domain and including all five depression factors, higher appetite-loss-related symptoms were associated with lower performance in episodic memory, psychomotor-executive functions, and verbal fluency; results were significant with covariates of age, education, race, sex, age of depression onset, and illness burden. No other depression factors were associated with neurocognitive performance in these models. In an additional set of models, the appetite factor mediated the association between global depression severity and neurocognitive performance. DISCUSSION: A factor of appetite and weight loss symptoms in LLD was uniquely associated with neurocognitive performance, in contrast to lack of association among other depression symptom factors. CONCLUSION: Cognitive deficits are a major adverse outcome of LLD, and prominent appetite loss during acute depression may be a marker for these deficits, independent of overall depression severity. Research is needed to understand the mechanisms that may explain this association, and how it is related to the cognitive and symptomatic course of LLD.

Disability but not social support predicts cognitive deterioration in late-life depression.

BACKGROUND: Depression in late life is a risk factor for cognitive decline. Depression is also associated with increased disability and social support deficits; these may precede conversion to dementia and inform risk. In this study, we examined if baseline or one-year change in disability and social support predicted later cognitive deterioration. METHODS: 299 cognitively intact depressed older adults were followed for an average of approximately seven years. Participants received antidepressant treatment according to a standardized algorithm. Neuropsychological testing and assessment of disability and social support were assessed annually. Cognitive diagnosis was reviewed annually at a consensus conference to determine if participants remained cognitively normal, or if they progressed to either dementia or cognitively impaired, no dementia (CIND). RESULTS: During study participation, 167 individuals remained cognitively normal (56%), 83 progressed to CIND (28%), and 49 progressed to dementia (16%). Greater baseline instrumental activities of daily living (IADL) deficits predicted subsequent conversion to a cognitive diagnosis (CIND or dementia). However, neither baseline measures nor one-year change in basic ADLs (BADLs) and social support predicted cognitive conversion. In post hoc analyses, two IADL measures (managing finances, preparing meals) significantly increased the odds of cognitive conversion. CONCLUSIONS: Greater IADL deficits predicted increased risk of cognitive conversion. Assessment of IADL deficits may provide clues about risk of later cognitive decline.

Hippocampus atrophy and the longitudinal course of late-life depression.

OBJECTIVES: Smaller hippocampal volumes are observed in depression but it remains unclear how antidepressant response and persistent depression relate to changes in hippocampal volume. We examined the longitudinal relationship between hippocampal atrophy and course of late-life depression. SETTING: Academic medical center. PARTICIPANTS: Depressed and never-depressed cognitively intact subjects age 60 years or older. MEASUREMENTS: Depression severity was measured every three months with the Montgomery-Asberg Depression Rating Scale (MADRS). Participants also completed cranial 1.5-T magnetic resonance imaging every 2 years. We compared 2-year change in hippocampal volume based on remission status, then in expanded analyses examined how hippocampal volumes predicted MADRS score. RESULTS: In analyses of 92 depressed and 70 never-depressed subjects, over 2 years the cohort whose depression never remitted exhibited greater hippocampal atrophy than the never-depressed cohort. In expanded analyses of a broader sample of 152 depressed elders, depression severity was significantly predicted by a hippocampus × time interaction where smaller hippocampus volumes over time were associated with greater depression severity. CONCLUSIONS: Hippocampal atrophy is associated with greater and persistent depression severity. Neuropathological studies are needed to determine if this atrophy is related to the toxic effects of persistent depression or related to underlying Alzheimer disease.

Elevated brain lesion volumes in older adults who use calcium supplements: a cross-sectional clinical observational study.

Recent studies have implicated Ca supplements in vascular risk elevation, and therefore these supplements may also be associated with the occurrence of brain lesions (or hyperintensities) in older adults. These lesions represent damage to brain tissue that is caused by ischaemia. In the present cross-sectional clinical observational study, the association between Ca-containing dietary supplement use and lesion volumes was investigated in a sample of 227 older adults (60 years and above). Food and supplemental Ca intakes were assessed with the Block 1998 FFQ; participants with supplemental Ca intake above zero were categorised as supplement users. Lesion volumes were determined from cranial MRI (1.5 tesla) scans using a semi-automated technique; volumes were log-transformed because they were non-normal. ANCOVA models revealed that supplement users had greater lesion volumes than non-users, even after controlling for food Ca intake, age, sex, race, years of education, energy intake, depression and hypertension (Ca supplement use: ß = 0.34, SE 0.10, F(1,217)= 10.98, P= 0.0011). The influence of supplemental Ca use on lesion volume was of a magnitude similar to that of the influence of hypertension, a well-established risk factor for lesions. Among the supplement users, the amount of supplemental Ca was not associated with lesion volume (ß = - 0.000035, SE 0.00 015, F(1,139)= 0.06, P= 0.81). The present study demonstrates that the use of Ca-containing dietary supplements, even low-dose supplements, by older adults may be associated with greater lesion volumes. Evaluation of randomised controlled trials is warranted to determine whether this relationship is a causal one.

Amnestic mild cognitive impairment and incident dementia and Alzheimer's disease in geriatric depression.

BACKGROUND: Memory impairment in geriatric depression is understudied, but may identify individuals at risk for development of dementia and Alzheimer's disease (AD). Using a neuropsychologically based definition of amnestic mild cognitive impairment (aMCI) in patients with geriatric depression, we hypothesized that patients with aMCI, compared with those without it, would have increased incidence of both dementia and AD. METHODS: Participants were aged 60 years and older and consisted of depressed participants and non-depressed volunteer controls. The depressed cohort met criteria for unipolar major depression. All participants were free of dementia and other neurological illness at baseline. At study entry, participants were administered a standardized clinical interview, a battery of neurocognitive tests, and provided a blood sample for determination of apolipoprotein E genotype. A cognitive diagnosis was assigned by a panel of experts who convened annually and reviewed available clinical, neuropsychological and laboratory data to achieve a consensus cognitive diagnosis to determine a consensus diagnosis. Survival analysis examined the association between aMCI and later dementia (all-cause) and AD. RESULTS: Among 295 depressed individuals, 63 (21.36%) met criteria for aMCI. Among 161 non-depressed controls, four (2.48%) met aMCI criteria. Participants were followed for 6.28 years on average. Forty-three individuals developed dementia, including 40 (13.6%) depressed and three (1.9%) control participants. Both aMCI and age were associated with incident dementia and AD. CONCLUSIONS: The presence of aMCI is a poor prognostic sign among patients with geriatric depression. Clinicians should carefully screen elderly depressed adults for memory impairment.

Clinical outcomes of older depressed patients with and without comorbid neuroticism.

BACKGROUND: Neuroticism is a psychological construct that includes tendency to exhibit negative affect (NA), having poor stress tolerance and being at risk for depression and anxiety disorders. The consequences of neuroticism in the elderly adults are understudied. We hypothesized that older depressed patients with comorbid neuroticism at baseline would have worse mood and cognitive outcomes compared with older depressed patients without neuroticism. METHODS: One hundred and ten older depressed adults completed baseline self-reports of depression and the NEO-Personality Inventory as a measure of neuroticism, were administered a battery of cognitive tests annually and were seen by a study psychiatrist who assessed patients using the Montgomery Åsberg Depression Rating Scale (MADRS) and treated patients with antidepressants using an established treatment guideline. Patients were followed as clinically indicated for up to three years. We measured remission (defined as MADRS score ≤ 6) rates at one year as a categorical outcome. In addition, we used Cox proportional hazard models to examine the relationship between neuroticism and change in MADRS and cognitive score over time. RESULTS: Non-remitters (30%) at one year had higher scores in total neuroticism (TN), vulnerability to stress (VS), and NA. Over three years, time to achieve remission was associated with higher TN, higher VS, and greater NA. In analyses controlling for baseline cognitive score, age, sex, and education, VS was associated with baseline to two-year change in cognition. CONCLUSIONS: Presence of neuroticism in older depressed patients treated with medication is associated with poor mood outcomes and may indicate increased risk of cognitive decline.

Reliable Cognitive Decline in Late-Life Major Depression.

OBJECTIVE: Major depression in older adults increases the statistical likelihood of dementia. It is challenging to translate statistical evidence of cognitive decline at the group level into knowledge of individual cognitive outcomes. The objective of the current study is to investigate 2-year reliable cognitive change in late-life depression (LLD), which will enhance understanding of cognitive changes in LLD and provide a means to assess individual change. METHODS: In a sample of non-depressed cognitively normal older adults or NDCN (n = 113), we used linear regression to predict tests of global cognition, processing speed-executive functioning, and memory administered 1 and 2 years later. Stepwise regression was used to select covariates among demographics and raw test scores (either baseline or year 1) and we cross-validated the final models using the predicted residual error sum of squares (PRESS). We then derived a z-change score from the difference between actual and predicted follow-up scores and investigated the proportion of LLD patients (n = 199) and NDCN adults who experienced reliable "decline" (a z-score < -1.645), "stability" (z-scores between + - 1.645), and "improvement" (z scores > +1.645). RESULTS: A greater proportion LLD compared with NDCN experienced cognitive decline in processing speed/executive functioning and global cognition over 2 years. When compared to NDCN, a greater proportion of LLD also significantly improved on one test of processing speed over 2 years. CONCLUSIONS: Older adults with LLD are at risk of meaningful cognitive decline over a relatively short period, particularly in the domain of executive functioning and processing speed. This study provides a series of reliable change equations for common neuropsychological tests that can be applied clinically.

Stressful life events, perceived stress, and 12-month course of geriatric depression: direct effects and moderation by the 5-HTTLPR and COMT Val158Met polymorphisms.

Although the relation between stressful life events (SLEs) and risk of major depressive disorder is well established, important questions remain about the effects of stress on the course of geriatric depression. Our objectives were (1) to examine how baseline stress and change in stress is associated with course of geriatric depression and (2) to test whether polymorphisms of serotonin transporter (5-HTTLPR) and catechol-O-methyltransferase (COMT Val158Met) genes moderate this relation. Two-hundred and sixteen depressed subjects aged 60 years or older were categorized by remission status (Montgomery-Asberg depression rating scale≤6) at 6 and 12 months. At 6 months, greater baseline numbers of self-reported negative and total SLEs and greater baseline perceived stress severity were associated with lower odds of remission. At 12 months, only baseline perceived stress predicted remission. When we examined change in stress, 12-month decrease in negative SLEs and level of perceived stress were associated with improved odds of 12-month remission. When genotype data were included, COMT Val158Met genotype did not influence these relations. However, when compared with 5-HTTLPR L/L homozygotes, S allele carriers with greater baseline numbers of negative SLEs and with greater decrease in negative SLEs were more likely to remit at 12 months. This study demonstrates that baseline SLEs and perceived stress severity may influence the 12-month course of geriatric depression. Moreover, changes in these stress measures over time correlate with depression outcomes. 5-HTTLPR S carriers appear to be more susceptible to both the effects of enduring stress and the benefit of interval stress reduction.

Association of attentional shift and reversal learning to functional deficits in geriatric depression.

OBJECTIVE: The objective of this study is to examine the association between self-reported functional disability in depressed older adults and two types of executive function processes, attentional set shifting and reversal learning. METHODS: Participants (N = 89) were aged 60 or over and enrolled in a naturalistic treatment study of major depressive disorder. Participants provided information on self-reported function in instrumental activities of daily living (IADL) and completed the Intra-Extra Dimensional Set Shift test (IED) from the Cambridge Neuropsychological Testing Automated Battery, which assesses intra-dimensional attentional shifts, extra-dimensional attentional shifts, and reversal learning. Participants were categorized by the presence or absence of IADL difficulties and compared on IED performance using bivariable and multivariable tests. RESULTS: Participants who reported IADL difficulties had more errors in extra-dimensional attentional shifting and reversal learning, but intra-dimensional shift errors were not associated with IADLs. Only extra-dimensional shift errors were significant in multivariable models that controlled for age, sex, and depression severity. CONCLUSIONS: Attentional shifting across categories (i.e., extra-dimensional) was most strongly associated with increased IADL difficulties among depressed older adults, which make interventions to improve flexible problem solving a potential target for reducing instrumental disability in this population.

AGTR1 gene variation: association with depression and frontotemporal morphology.

The renin-angiotensin system (RAS) is implicated in the response to physiological and psychosocial stressors, but its role in stress-related psychiatric disorders is poorly understood. We examined if variation in AGTR1, the gene coding for the type 1 angiotensin II receptor (AT(1)R), is associated with a diagnosis of depression and differences in white matter hyperintensities and frontotemporal brain volumes. Participants comprised 257 depressed and 116 nondepressed elderly Caucasian subjects who completed clinical assessments and provided blood samples for genotyping. We used a haplotype-tagging single nucleotide polymorphism (htSNP) analysis to test for variation in AGTR1. For measurement of hyperintense lesions, 1.5 Tesla magnetic resonance imaging (MRI) data were available on 33 subjects. For measurements of the hippocampus and dorsolateral prefrontal cortex (dlPFC), 3 Tesla MRI data were available on 70 subjects. Two htSNPs exhibited statistically significant frequency differences between diagnostic cohorts: rs10935724 and rs12721331. Although hyperintense lesion volume did not significantly differ by any htSNP, dlPFC and hippocampus volume differed significantly for several htSNPs. Intriguingly, for those htSNPs differing significantly for both dlPFC and hippocampus volume, the variant associated with smaller dlPFC volume was associated with larger hippocampal volume. This supports the idea that genetic variation in AGTR1 is associated with depression and differences in frontotemporal morphology.

Change in hippocampal volume on magnetic resonance imaging and cognitive decline among older depressed and nondepressed subjects in the neurocognitive outcomes of depression in the elderly study.

INTRODUCTION: previous studies have linked hippocampal volume change and cognitive decline in older adults with dementia. The authors examined hippocampal volume change and cognitive change in older nondemented adults with and without major depression. METHODS: the sample consisted of 90 depressed individuals and 72 healthy, nondepressed individuals aged 60 years and older who completed at least 2 years of follow-up data. All patients underwent periodic clinical evaluation by a geriatric psychiatrist as well as baseline and 2-year magnetic resonance imaging. RESULTS: over 2 years, the depressed group showed a greater reduction in left hippocampal volume (normalized for total cerebral volume) compared with the nondepressed group (mean difference = 0.013 ± 0.0059, t = 2.18, df = 160, p <0.0305). The difference remained significant after controlling for age, sex, and baseline normalized left hippocampal volume. The authors also found that hippocampal change from baseline to 2 years was associated with subsequent change in Mini-Mental State Examination score from 2 years to 2½ years (left t = 2.81, df = 66, p = 0.0066; right t = 2.40, df = 66, p = 0.0193) among the depressed group. CONCLUSIONS: these findings add to the literature linking hippocampal volume loss and late-life depression. Depressed patients with hippocampal volume loss are at greater risk of cognitive decline.

Social support modifies the relationship between personality and depressive symptoms in older adults.

OBJECTIVE: To explore the relationship between personality, social support, and depression in older adults, identify the personality trait and social support dimension most closely associated with depression, and determine whether the relationship between personality and depression varies by level of social support. DESIGN: Cross-sectional analysis within longitudinal study. PARTICIPANTS: Older patients originally diagnosed with major depression (n = 108) and never-depressed comparison group of older adults (n = 103). MEASUREMENTS: Patients sufficiently recovered from major depression and comparison participants were administered the NEO Personality Inventory. Social support was measured annually for both groups. Patients were administered the Montgomery-Asberg Depression Rating Scale (MADRS) every 3 months. RESULTS: Patients and comparison participants differed on four of the five NEO domains and all four social support dimensions, but personality did not significantly predict depression status (patient/comparison) in controlled analyses. Within the patient group, subjective social support was the only dimension correlated with MADRS score. In separate linear regression analyses among the patients, controlling for age, sex, and subjective social support, the domains of Neuroticism, Openness to Experience, Conscientiousness, and Extraversion were associated with MADRS score. For Neuroticism and Openness, the association varied by level of subjective social support. CONCLUSIONS: Our research confirmed that older patients differed from never-depressed older adults in dimensions of personality and social support, and the relationship between these variables differed by depression status. The relationship between personality, social support, and depressive symptoms in older adults recovering from depression is also complex, with subjective social support modifying the association between personality and depression.

Amygdala volume in late-life depression: relationship with age of onset.

OBJECTIVES: Depression is common in the elderly population. Although numerous neuroimaging studies have examined depressed elders, there is limited research examining how amygdala volume may be related to depression. DESIGN: A cross-sectional examination of amygdala volume comparing elders with and without a diagnosis of major depressive disorder, and between depressed subjects with early and later initial depression onset. SETTING: An academic medical center. PARTICIPANTS: Ninety-one elderly patients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for major depression (54 early-onset depressed and 37 late-onset depressed) and 31 elderly subjects without any psychiatric diagnoses. MEASUREMENTS: Amygdala and cerebral volumes were measured using reliable manual tracing methods. RESULTS: In models controlling for age, sex, and cerebral volume, there was a significant difference between diagnostic cohorts in amygdala volume bilaterally (left: F[2, 116] = 16.28, p < 0.0001; right: F[2, 116] = 16.28, p < 0.0001). Using least squares mean group analyses, both early- and late-onset depressed subjects exhibited smaller bilateral amygdala volumes than did the nondepressed cohort (all comparisons p < 0.0001), but the two depressed cohorts did not exhibit a statistically significant difference. LIMITATIONS: Limitations include missing antidepressant treatment data, recall bias, inability to establish a causal relationship between amygdala size and depression given the cross-sectional nature of the design. CONCLUSIONS: Depression in later life is associated with smaller amygdala volumes, regardless of age of initial onset of depression.

Change in stress and social support as predictors of cognitive decline in older adults with and without depression.

OBJECTIVE: The relationship between stress, social support, and cognition in geriatric depression is complex. In this study, we sought to examine whether an increase in stressful life events or a decrease in social support would lead to subsequent cognitive decline among older adults with and without depression. METHODS: The sample consisted of 112 depressed and 101 non-depressed older adults who enrolled in the Neurocognitive Outcomes of Depression in the Elderly (NCODE) study. Participants were assessed clinically, agreed to interviews focusing on stressful life events and social support, and underwent a battery of neuropsychological tests annually. Our global measure of cognition was the Consortium to Establish a Registry in Alzheimer's disease Total Score (CERAD TS). RESULTS: We found that a decline in the total number of stressors was associated with a subsequent improvement on CERAD TS. In terms of social support, decreased social interaction, and instrumental social support predicted decline in cognitive performance. These relationships were significant even after controlling for depression status, age, education, and sex. CONCLUSIONS: These findings extend prior research on the importance of social factors in aging and depression which have largely focused on mood-related outcomes. Future confirmatory studies are needed. In addition, biological and other studies should be conducted to further our understanding of the relationship between stress, social support and cognition in older adults with and without depression.

Reduction of dorsolateral prefrontal cortex gray matter in late-life depression.

Postmortem studies have documented abnormalities in the dorsolateral prefrontal cortex (dlPFC) in depressed subjects. In this study we used magnetic resonance imaging to test for dlPFC volume differences between older depressed and non-depressed individuals. Eighty-eight subjects meeting DSM IV criteria for major depressive disorder and thirty-five control subjects completed clinical evaluations and cranial 3T magnetic resonance imaging. After tissue types were identified using an automated segmentation process, the dlPFC was measured in both hemispheres using manual delineation based on anatomical landmarks. Depressed subjects had significantly lower gray matter in the left and right dorsolateral prefrontal cortex (standardized to cerebral parenchyma) after controlling for age and sex. Our study confirmed the reduction of dorsolateral prefrontal cortex in elderly depressed subjects, especially in the gray matter. These regional abnormalities may be associated with psychopathological changes in late-life depression.