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Examining the association between late-life depressive symptoms, cognitive function, and brain volumes in the context of cognitive reserve.

ABSTRACT: The present study aimed to investigate whether cognitive reserve moderated the association between depressive symptoms and cognition, as well as brain volumes in a sample of older adults.Non-demented participants (n = 3484) were selected from the Washington Heights/Hamilton Heights Inwood Columbia Aging Project (Northern Manhattan). A subsample of these participants without dementia (n = 703), who had brain imaging data, was also selected for a separate analysis. Depressive symptomatology was assessed with the 10-item Center for Epidemiologic Studies Depression Scale. Reading level and years of education were used as measures of cognitive reserve. Four distinct cognitive composite scores were calculated: executive function, memory, visual-spatial, and language.Multiple regression analysis revealed interaction effects between both measures of cognitive reserve and depressive symptoms on all the cognitive outcome measures except for visual-spatial ability. Those with greater reserve showed greater cognitive decrements than those with lower levels of reserve as depressive symptoms increased. A borderline interaction effect was revealed between reading level and depressive symptoms on total brain volumes. Those with lower reading scores showed greater volume loss as depressive symptoms increased than those with higher reading scores.Our findings indicate that the association between late-life depressive symptoms and core aspects of cognition varies depending on one's level of cognitive reserve. Those that had greater levels of education and/or reading ability showed a greater decrease in memory, executive, and language performances as depressive symptoms increased than those with lower years of education and reading ability.

SUBMITTER: O'Shea DM

PROVIDER: S-EPMC4336836 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Examining the association between late-life depressive symptoms, cognitive function, and brain volumes in the context of cognitive reserve.

O'Shea Deirdre M DM Fieo Robert A RA Hamilton Jamie L JL Zahodne Laura B LB Manly Jennifer J JJ Stern Yaakov Y

International journal of geriatric psychiatry 20140822 6

<h4>Objective</h4>The present study aimed to investigate whether cognitive reserve moderated the association between depressive symptoms and cognition, as well as brain volumes in a sample of older adults.<h4>Methods</h4>Non-demented participants (n = 3484) were selected from the Washington Heights/Hamilton Heights Inwood Columbia Aging Project (Northern Manhattan). A subsample of these participants without dementia (n = 703), who had brain imaging data, was also selected for a separate analysis ...[more]

PMID: 25145832

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Project description:ImportanceThe neurobiologic basis of late-life depressive symptoms is not well understood.ObjectiveTo test the hypothesis that neurodegeneration and neuronal density in brainstem aminergic nuclei are related to late-life depressive symptoms. DESIGN, SETTING, PARTICIPANTS, AND EXPOSURE: Longitudinal clinicopathological cohort study at residences of participants in the Chicago, Illinois, metropolitan area. Participants included 124 older persons without dementia in the Rush Memory and Aging Project who had annual evaluations for a mean (SD) of 5.7 (2.8) years, died, and underwent a postmortem neuropathological examination that provided estimates of the densities of Lewy bodies, neurofibrillary tangles, and aminergic neurons in the locus ceruleus, dorsal raphe nucleus, substantia nigra, and ventral tegmental area.Main outcomes and measuresThe number of depressive symptoms (mean [SD], 1.61 [1.48]; range, 0-6; skewness, 0.94) on the Center for Epidemiological Studies Depression Scale averaged across annual evaluations.ResultsBrainstem Lewy bodies were associated with depressive symptoms, and the association was attenuated in those taking antidepressant medication. Brainstem tangles were associated with more depressive symptoms in those without cognitive impairment but with fewer symptoms in those with mild cognitive impairment. Lower density of tyrosine hydroxylase-immunoreactive neurons in the ventral tegmental area was robustly associated with a higher level of depressive symptoms (mean [SE] estimate, -0.014 [0.003]; P < .001; 16.3% increase in adjusted R2). The association was not modified by medication use or cognitive impairment. Neither tyrosine hydroxlyase-immunoreactive neurons in the locus ceruleus nor tryptophan hydroxlyase-immunoreactive neurons in the dorsal raphe nucleus were related to depressive symptoms.Conclusions and relevanceThe results suggest that the mesolimbic dopamine system, especially the ventral tegmental area, has an important role in late-life depressive symptoms.

Project description:BackgroundAlthough electroconvulsive therapy (ECT) is an effective treatment for depression, ECT cognitive impairment remains a major concern. The neurobiological underpinnings and mechanisms underlying ECT antidepressant and cognitive impairment effects remain unknown. This investigation aims to identify ECT antidepressant-response and cognitive-impairment multimodal brain networks and assesses whether they are associated with the ECT-induced electric field (E-field) with an optimal pulse amplitude estimation.MethodsA single site clinical trial focused on amplitude (600, 700, and 800 mA) included longitudinal multimodal imaging and clinical and cognitive assessments completed before and immediately after the ECT series (n = 54) for late-life depression. Another two independent validation cohorts (n = 84, n = 260) were included. Symptom and cognition were used as references to supervise fMRI and sMRI fusion to identify ECT antidepressant-response and cognitive-impairment multimodal brain networks. Correlations between ECT-induced E-field within these two networks and clinical and cognitive outcomes were calculated. An optimal pulse amplitude was estimated based on E-field within antidepressant-response and cognitive-impairment networks.ResultsDecreased function in the superior orbitofrontal cortex and caudate accompanied with increased volume in medial temporal cortex showed covarying functional and structural alterations in both antidepressant-response and cognitive-impairment networks. Volume increases in the hippocampal complex and thalamus were antidepressant-response specific, and functional decreases in the amygdala and hippocampal complex were cognitive-impairment specific, which were validated in two independent datasets. The E-field within these two networks showed an inverse relationship with HDRS reduction and cognitive impairment. The optimal E-filed range as [92.7-113.9] V/m was estimated to maximize antidepressant outcomes without compromising cognitive safety.ConclusionsThe large degree of overlap between antidepressant-response and cognitive-impairment networks challenges parameter development focused on precise E-field dosing with new electrode placements. The determination of the optimal individualized ECT amplitude within the antidepressant and cognitive networks may improve the treatment benefit-risk ratio.Trial registrationClinicalTrials.gov Identifier: NCT02999269.

Dataset Information

Examining the association between late-life depressive symptoms, cognitive function, and brain volumes in the context of cognitive reserve.

Publications

Examining the association between late-life depressive symptoms, cognitive function, and brain volumes in the context of cognitive reserve.

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