Journal article
Integrating contextual determinants and polygenic risk to examine dementia and late-life cognition in the Multi-Ethnic Study of Atherosclerosis
Alzheimer's & dementia, v 22(4), e71384
Apr 2026
PMID: 41988869
Featured in Collection : Drexel's Newest Publications
Abstract
Alzheimer's disease and related dementias are influenced by genetic and environmental risk factors. We investigated the relationship between contextual exposures and cognitive outcomes, independent of and in interaction with polygenic risk.
Using the Multi-Ethnic Study of Atherosclerosis (N = 5687), we assessed the associations of contextual determinants representing the social, chemical, and built environment with incident dementia and late-life cognition using proportional hazards regression and generalized estimating equation models, then evaluated their joint effects stratified by genetic risk via Bayesian kernel machine regression.
Neighborhood disadvantage was associated with higher dementia risk and poorer cognitive scores after adjusting for genetic risk and other individual-level covariates. Joint analysis of all contextual determinants indicated that more deleterious mixtures of contextual determinants are associated with lower late-life cognition among apolipoprotein E ɛ4 non-carriers with intermediate polygenic risk.
Contextual determinants are associated with dementia and late-life cognition after adjusting for age, sex, education, and genetic risk.
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Details
- Title
- Integrating contextual determinants and polygenic risk to examine dementia and late-life cognition in the Multi-Ethnic Study of Atherosclerosis
- Creators
- Diane Xue (Corresponding Author) - University of PennsylvaniaJana A Hirsch - Drexel UniversityLilah Besser - University of Miami Health SystemTimothy M Hughes - Wake Forest UniversityElizabeth E Blue - University of WashingtonAnnette L Fitzpatrick - University of WashingtonAlison E Fohner - University of Washington
- Publication Details
- Alzheimer's & dementia, v 22(4), e71384
- Publisher
- Wiley; HOBOKEN
- Number of pages
- 12
- Grant note
- N01-HC-95160 / Broad Institute of Harvard and MIT (Boston, Massachusetts, USA) MESA Publications and Presentations Committee N01-HC-95169 / Broad Institute of Harvard and MIT (Boston, Massachusetts, USA) N01-HC-95161 / Broad Institute of Harvard and MIT (Boston, Massachusetts, USA) 75N92020D00002 / NHLBI NIH HHS UL1-TR-001079 / NHLBI NIH HHS K01AG071689 / NIA NIH HHS N01-HC-95162 / Broad Institute of Harvard and MIT (Boston, Massachusetts, USA) 75N92020D00005 / NHLBI NIH HHS N01-HC-95168 / Broad Institute of Harvard and MIT (Boston, Massachusetts, USA)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Urban Health Collaborative; Epidemiology and Biostatistics
- Web of Science ID
- WOS:001741549500001
- Other Identifier
- 991022173526404721