Dataset Information

Plasma proteomic signatures predict dementia and cognitive impairment.

ABSTRACT: Introduction:Biomarker discovery of dementia and cognitive impairment is important to gather insight into mechanisms underlying the pathogenesis of these conditions. Methods:In 997 adults from the InCHIANTI study, we assessed the association of 1301 plasma proteins with dementia and cognitive impairment. Validation was conducted in two Alzheimer's disease (AD) case-control studies as well as endophenotypes of AD including cognitive decline, brain amyloid burden, and brain volume. Results:We identified four risk proteins that were significantly associated with increased odds (peptidase inhibitor 3 (PI3), trefoil factor 3 (TFF3), pregnancy associated plasma protein A (PAPPA), agouti-related peptide (AGRP)) and two protective proteins (myostatin (MSTN), integrin aVb5 (ITGAV/ITGB5)) with decreased odds of baseline cognitive impairment or dementia. Of these, four proteins (MSTN, PI3, TFF3, PAPPA) were associated cognitive decline in subjects that were cognitively normal at baseline. ITGAV/ITGB5 was associated with lower brain amyloid burden, MSTN and ITGAV/ITGB5 were associated with larger brain volume and slower brain atrophy, and PI3, PAPPA, and AGRP were associated with smaller brain volume and/or faster brain atrophy. Discussion:These proteins may be useful as non-invasive biomarkers of dementia and cognitive impairment.

SUBMITTER: Tanaka T

PROVIDER: S-EPMC7210784 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Plasma proteomic signatures predict dementia and cognitive impairment.

Tanaka Toshiko T Lavery Robert R Varma Vijay V Fantoni Giovanna G Colpo Marco M Thambisetty Madhav M Candia Julian J Resnick Susan M SM Bennett David A DA Biancotto Angelique A Bandinelli Stefania S Ferrucci Luigi L

Alzheimer's & dementia (New York, N. Y.) 20200509 1

<h4>Introduction</h4>Biomarker discovery of dementia and cognitive impairment is important to gather insight into mechanisms underlying the pathogenesis of these conditions.<h4>Methods</h4>In 997 adults from the InCHIANTI study, we assessed the association of 1301 plasma proteins with dementia and cognitive impairment. Validation was conducted in two Alzheimer's disease (AD) case-control studies as well as endophenotypes of AD including cognitive decline, brain amyloid burden, and brain volume.< ...[more]

PMID: 32607407

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Project description:Experiencing decline in both cognition and mobility is associated with a substantially higher dementia risk than cognitive decline only. Metabolites associated with both cognitive and mobility declines may be early predictors of dementia and reveal specific pathways to dementia. We analyzed data from 2450 participants initially free of dementia who had 613 metabolites measured in plasma in 1998-1999 (mean age = 75.2 ± 2.9 years old, 37.8% Black, 50% women) from the Health, Aging and Body Composition study. Dementia diagnosis was determined by race-specific decline in 3MS scores, medication use, and hospital records through 2014. Cognition and mobility were repeatedly measured using 3MS and a 20-m walking test up to 10 years, respectively. We examined metabolite associations with changes in 3MS (n = 2046) and gait speed (n = 2019) using multivariable linear regression adjusted for age, sex, race, and baseline performance and examined metabolite associations with dementia risk using Cox regression. During a mean follow-up of 9.3 years, 534 (21.8%) participants developed dementia. On average, 3MS declined 0.47/year and gait declined 0.04 m/sec/year. After covariate adjustment, 75 metabolites were associated with cognitive decline, and 111 metabolites were associated with gait decline (FDR-adjusted p < 0.05). Twenty-six metabolites were associated with both cognitive and gait declines. Eighteen of 26 metabolites were associated with dementia risk (p < 0.05), notably amino acids, glycerophospholipids (lysoPCs, PCs, PEs), and sphingolipids. Results remained similar after adjusting for cardiovascular disease or apolipoprotein E ɛ4 carrier status. During aging, metabolomic profiles of cognitive decline and mobility decline show distinct and shared signatures. Shared metabolomic profiles suggest that inflammation and deficits in mitochondria and the urea cycle in addition to the central nervous system may play key roles in both cognitive and mobility declines and predict dementia. Future studies are warranted to investigate longitudinal metabolite changes and metabolomic markers with dementia pathologies.

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Plasma proteomic signatures predict dementia and cognitive impairment.

Publications

Plasma proteomic signatures predict dementia and cognitive impairment.

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