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Psychosocial Risk Factors for Cognitive Decline in Late-Life Depression: Findings from the MTLD-III Study.

ABSTRACT: BACKGROUND:Cognitive impairment and depression frequently co-occur in late life. There remains a need to better characterize psychosocial risk factors of cognitive decline in older adults with depression. We hypothesized that certain psychosocial factors would be associated with higher risk of cognitive decline in individuals with late-life depression. METHODS:130 individuals aged ? 65 years who had achieved remission from a major depressive episode were randomized to donepezil or placebo and then closely followed for two years. Using Cox proportional hazard models, we examined the association between baseline median household income, education level, race, marital status, and social support and cognitive decline over the follow-up. RESULTS:Lower interpersonal support (OR = 0.86 [0.74-0.99], p = .04) and lower baseline global neuropsychological score (OR = 0.56 [0.36-0.87], p = .001) predicted shorter time to conversion to MCI or dementia in univariate models. These exposures did not remain significant in multivariate analyses. Neither socioeconomic status nor other psychosocial factors independently predicted cognitive diagnostic conversion (p > .05). CONCLUSIONS:We did not find reliable associations between cognitive outcome and any of the psychosocial factors examined. Future large-scale, epidemiological studies, ideally using well-validated subjective measures, should better characterize psychosocial risk factors for cognitive decline in late-life depression.

SUBMITTER: Rej S

PROVIDER: S-EPMC4487735 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Psychosocial Risk Factors for Cognitive Decline in Late-Life Depression: Findings from the MTLD-III Study.

Rej Soham S Begley Amy A Gildengers Ariel A Dew Mary Amanda MA Reynolds Charles F CF Butters Meryl A MA

Canadian geriatrics journal : CGJ 20150630 2

<h4>Background</h4>Cognitive impairment and depression frequently co-occur in late life. There remains a need to better characterize psychosocial risk factors of cognitive decline in older adults with depression. We hypothesized that certain psychosocial factors would be associated with higher risk of cognitive decline in individuals with late-life depression.<h4>Methods</h4>130 individuals aged ≥ 65 years who had achieved remission from a major depressive episode were randomized to donepezil or ...[more]

PMID: 26180559

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Project description:ObjectiveThis study sought to conduct a comprehensive search for genetic risk of cognitive decline in the context of geriatric depression.DesignA genome-wide association study (GWAS) analysis in the Neurocognitive Outcomes of Depression in the Elderly (NCODE) study.SettingLongitudinal, naturalistic follow-up study.ParticipantsOlder depressed adults, both outpatients and inpatients, receiving care at an academic medical center.MeasurementsThe 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.ResultsThe 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.ConclusionsOur 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.

Project description:Late-life depression (LLD) and amnestic mild cognitive impairment (aMCI) are associated with medial temporal lobe structural abnormalities. However, the hippocampal functional connectivity (HFC) similarities and differences related to these syndromes when they occur alone or coexist are unclear. Resting-state functional connectivity MRI (R-fMRI) technique was used to measure left and right HFC in 72 elderly participants (LLD [n = 18], aMCI [n = 17], LLD with comorbid aMCI [n = 12], and healthy controls [n = 25]). The main and interactive relationships of LLD and aMCI on the HFC networks were determined, after controlling for age, gender, education and gray matter volumes. The effects of depressive symptoms and episodic memory deficits on the hippocampal functional connections also were assessed. While increased and decreased left and right HFC with several cortical and subcortical structures involved in mood regulation were related to LLD, aMCI was associated with globally diminished connectivity. Significant LLD-aMCI interactions on the right HFC networks were seen in the brain regions critical for emotion processing and higher-order cognitive functions. In the interactive brain regions, LLD and aMCI were associated with diminished hippocampal functional connections, whereas the comorbid group demonstrated enhanced connectivity. Main and interactive effects of depressive symptoms and episodic memory performance were also associated with bilateral HFC network abnormalities. In conclusion, these findings indicate that discrete hippocampal functional network abnormalities are associated with LLD and aMCI when they occur alone. However, when these conditions coexist, more pronounced vulnerabilities of the hippocampal networks occur, which may be a marker of disease severity and impending cognitive decline. By utilizing R-fMRI technique, this study provides novel insights into the neural mechanisms underlying LLD and aMCI in the functional network level.

Project description:ObjectiveThere is variability across individuals in cognitive aging. To investigate the associations of several modifiable factors with high and low cognitive performance.MethodsData came from 17,724 community-dwelling individuals aged 65-98 years. Global cognition, verbal fluency, episodic memory, and psychomotor speed were assessed over up to seven years. Group-based multi-trajectory modeling identified distinct cognitive trajectories. Structural equation modeling examined the direct/indirect associations of social/behavioral factors and several chronic conditions with cognitive trajectories.ResultsSeven trajectory subgroups were identified. In the structural equation modeling we compared two subgroups-participants with the highest (14.2%) and lowest (4.1%) cognitive performance with the average subgroup. Lower education, never alcohol intake, and frailty directly predicted increased risk of low performance, and decreased likelihood of high performance. Hypertension (RR: 0.69, 95%CI: 0.60-0.80), obesity (RR: 0.84, 95%CI: 0.73-0.97), diabetes (RR: 0.69, 95%CI: 0.56-0.86) and depression (RR: 0.68, 95%CI: 0.54-0.85) only predicted lower likelihood of high cognitive performance, while dyslipidemia was only associated with low performance (RR: 1.30, 95%CI: 1.07-1.57). Living alone predicted increased risk of low cognitive performance and several comorbidities. Smoking did not predict cognitive trajectories but was associated with increased risk of diabetes, obesity and frailty. Findings were similar when examining the direct associations between modifiable risk factors and all seven cognitive subgroups.ConclusionsAlthough several modifiable factors were associated with high performance, and reversely with low performance, this was not observed for obesity, hypertension and dyslipidemia. Further, health behaviors may affect cognitive function indirectly, via geriatric conditions. This indicates that strategies to promote healthy cognitive aging, may be distinct from those targeting dementia prevention.

Dataset Information

Psychosocial Risk Factors for Cognitive Decline in Late-Life Depression: Findings from the MTLD-III Study.

Publications

Psychosocial Risk Factors for Cognitive Decline in Late-Life Depression: Findings from the MTLD-III Study.

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