Dataset Information

Correlated decline of cognitive and motor phenotypes and ADRD pathologies in old age.

ABSTRACT:

Introduction

Examining motor and cognitive decline in separate models may underestimate their associations.

Methods

In a single trivariate model, we examined the levels and rates of decline of three phenotypes, sensor-derived total daily physical activity, motor abilities, and cognition in 1007 older adults during 6 years of follow-up. In 477 decedents, we repeated the model adding fixed terms for indices of nine brain pathologies.

Results

Simultaneous rates of decline of all three phenotypes showed the strongest correlations with shared variance of up to 50%. Brain pathologies explained about 3% of the variance of declining daily physical activity, 9% of declining motor abilities, and 42% of cognitive decline.

Discussion

The rates of declining cognitive and motor phenotypes are strongly correlated and measures of brain pathologies account for only a small minority of their decline. Further work is needed to elucidate the biology underlying correlated cognitive and motor decline in aging adults.

SUBMITTER: Buchman AS

PROVIDER: S-EPMC10524791 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

Correlated decline of cognitive and motor phenotypes and ADRD pathologies in old age.

Buchman Aron S AS Wang Tianhao T Oveisgharan Shahram S Zammit Andrea R AR Agrawal Sonal S Yu Lei L Bennett David A DA

Alzheimer's & dementia : the journal of the Alzheimer's Association 20230612 9

<h4>Introduction</h4>Examining motor and cognitive decline in separate models may underestimate their associations.<h4>Methods</h4>In a single trivariate model, we examined the levels and rates of decline of three phenotypes, sensor-derived total daily physical activity, motor abilities, and cognition in 1007 older adults during 6 years of follow-up. In 477 decedents, we repeated the model adding fixed terms for indices of nine brain pathologies.<h4>Results</h4>Simultaneous rates of decline of a ...[more]

PMID: 37303291

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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

Correlated decline of cognitive and motor phenotypes and ADRD pathologies in old age.

Introduction

Methods

Results

Discussion

Publications

Correlated decline of cognitive and motor phenotypes and ADRD pathologies in old age.

Similar Datasets

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