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Clinical-pathologic study of depressive symptoms and cognitive decline in old age.

ABSTRACT: To clarify the relationship between depressive symptoms and the clinical and neuropathologic manifestations of dementia.In a clinical-pathologic cohort study, 1,764 older persons without cognitive impairment at enrollment completed annual clinical evaluations for a mean of 7.8 years. The evaluations included assessment of depressive symptoms (10-item Center for Epidemiological Studies Depression Scale) and cognitive function (battery of 17 performance tests). A total of 582 individuals died during follow-up and underwent a uniform neuropathologic examination to quantify ?-amyloid plaques and tau tangle density in multiple brain regions and identify neocortical Lewy bodies, hippocampal sclerosis, and gross and microscopic cerebral infarcts.Level of depressive symptoms slightly increased during follow-up. Incident mild cognitive impairment (52.2%) was associated with higher level of depressive symptoms before the diagnosis but not with change in symptoms after the diagnosis; incident dementia (17.9%) was associated with higher symptom level before dementia onset and with more rapid decline in symptoms after dementia onset. None of the neuropathologic markers was related to level of depressive symptoms or change in symptoms over time. In a mixed-effects model adjusted for the neuropathologic markers, higher level of depressive symptoms averaged over evaluations was associated with more rapid global cognitive decline, accounting for 4.4% of the variability in decline not attributable to the neuropathologic markers. Depressive symptoms did not modify the association of the neuropathologic markers with cognitive decline.In old age, depressive symptoms have an association with cognitive decline that is independent of the neuropathologic hallmarks of dementia.

SUBMITTER: Wilson RS

PROVIDER: S-EPMC4150132 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Clinical-pathologic study of depressive symptoms and cognitive decline in old age.

Wilson Robert S RS Capuano Ana W AW Boyle Patricia A PA Hoganson George M GM Hizel Loren P LP Shah Raj C RC Nag Sukriti S Schneider Julie A JA Arnold Steven E SE Bennett David A DA

Neurology 20140730 8

<h4>Objective</h4>To clarify the relationship between depressive symptoms and the clinical and neuropathologic manifestations of dementia.<h4>Methods</h4>In a clinical-pathologic cohort study, 1,764 older persons without cognitive impairment at enrollment completed annual clinical evaluations for a mean of 7.8 years. The evaluations included assessment of depressive symptoms (10-item Center for Epidemiological Studies Depression Scale) and cognitive function (battery of 17 performance tests). A ...[more]

PMID: 25080520

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Project description:ImportanceCognitive decline is a leading cause of disability and death in old age but its neurobiological bases are not well understood.ObjectiveTo test the hypothesis that transactive response DNA-binding protein 43 (TDP-43) is related to late-life cognitive decline.Design, setting, and participantsLongitudinal clinical-pathologic cohort study involving more than 40 Catholic groups across the United States. A total of 130 older Catholic nuns, priests, and monks underwent annual clinical evaluations, including detailed cognitive testing, for a mean of 10.1 years prior to death. On neuropathologic examination, we collected semiquantitative measures of TDP-43 pathology, density of neuronal neurofibrillary tangles, area occupied by amyloid-beta plaques, and the presence of alpha-synuclein Lewy bodies from multiple brain regions. Gross and microscopic cerebral infarcts and hippocampal sclerosis were also identified.Main outcomes and measuresAnnual rate of change in a previously established composite measure of global cognition during a mean of 10.1 years of annual observation before death.ResultsTransactive response DNA-binding protein 43 pathology, ranging from sparse to severe, was identified in 46% of participants and was associated with amyloid plaques, tangles, and hippocampal sclerosis but not neocortical Lewy bodies or cerebral infarcts. After controlling for amyloid plaques, tangles, and hippocampal sclerosis, TDP-43 pathology was associated with more rapid cognitive decline and accounted for nearly as much of the variability in rates of global cognitive decline as did tangles. Transactive response DNA-binding protein 43 pathology had a distinct cognitive profile that differed from other neuropathologic processes (related to decline in episodic and working memory but not in other cognitive domains), and it was elevated in those who developed dementia but not in those with mild cognitive impairment.Conclusion and relevanceThe results suggest that TDP-43 is an important brain pathology underlying cognitive decline and dementia in old age.

Dataset Information

Clinical-pathologic study of depressive symptoms and cognitive decline in old age.

Publications

Clinical-pathologic study of depressive symptoms and cognitive decline in old age.

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