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Innov Aging
Innov Aging
innovateage
Innovation in Aging
2399-5300 Oxford University Press US 

10.1093/geroni/igaa057.1671
igaa057.1671
Abstracts
Session 3018 (Symposium)
ESPO/ Biological Sciences Section Symposium: Understanding the Complex and Interconnected Pathways of Aging
AcademicSubjects/SOC02600
Circulating Cell-Free DNA Is Associated With Cognitive Outcomes
Feger Danielle 1 Nidadavolu Lolita 1 Oh Esther 2 Abadir Peter 2 Gross Alden 3 1 
Johns Hopkins University, Baltimore, Maryland, United States
2 
Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
3 
Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States
2020 
16 12 2020 
16 12 2020 
4 Suppl 1 Program Abstracts from The GSA 2020 Annual Scientific Meeting “Turning 75: Why Age Matters”518 518
© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America.2020This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.Abstract
Cell death is a mechanism by which aging tissues are able to maintain homeostasis. DNA of nuclear and mitochondrial origin is released into circulation following apoptosis or necroptosis and can be quantified in the blood as circulating cell-free DNA (ccf-DNA). We hypothesized that higher levels of ccf-DNA would be associated with worse cognitive function. Ultra-sensitive digital PCR was used to measure ccf-DNA in participants from the Rush Alzheimer’s Disease Center Religious Orders Study/Memory and Aging Project. Global cognitive function was derived from a composite of 19 tests on a neuropsychiatric battery. A total of 885 ccf-DNA samples were analyzed from N=624 participants. Generalized estimating equations were used to estimate the cross-sectional association between ccf-DNA and global cognition scores, while latent growth models were used to estimate the longitudinal association between ccf-DNA and global cognition scores. Multinomial logistic regression was used to estimate the odds of having mild cognitive impairment (MCI) or dementia at last study visit relative to normal cognition, based on levels of ccf-DNA. Higher ccf-DNA levels were associated with lower global cognition score (-0.10, [-0.18, -0.02]) cross-sectionally. Each 1-standard deviation increase in ccf-DNA was associated with more rapidly declining global cognitive function over time (-0.11, [-0.19, -0.03]). A dose-response relationship was observed between increasing levels of ccf-DNA and odds of MCI (odds ratio [OR] = 1.08, [0.83, 1.41]) and dementia (OR = 1.29, [1.06, 1.57]). Our results suggest that ccf-DNA may serve as a biomarker of global cognitive decline and dementia risk.