Cardiovascular health, genetic risk, and risk of dementia in the Framingham Heart Study

Gina M. Peloso, Alexa S. Beiser, Claudia L. Satizabal, Vanessa Xanthakis, Ramachandran S. Vasan, Matthew P. Pase, Anita L. Destefano, Sudha Seshadri

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Objective: To determine the joint role of ideal cardiovascular health (CVH) and genetic risk on risk of dementia. Methods:We categorized CVH on the basis of the American Heart Association Ideal CVH Index and genetic risk through a genetic risk score (GRS) of common genetic variants and the APOE ϵ4 genotype in 1,211 Framingham Heart Study (FHS) offspring cohort participants. We used multivariable Cox proportional hazards regression models to examine the association between CVH, genetic risk, and incident all-cause dementia with up to 10 years of follow-up (mean 8.4 years, 96 incident dementia cases), adjusting for age, sex, and education. Results:We observed that a high GRS (>80th percentile) was associated with a 2.6-fold risk of dementia (95% confidence interval [CI] of hazard ratio [HR] 1.23-5.29; p = 0.012) compared with having a low GRS (<20th percentile); carrying at least 1 APOE ϵ4 allele was associated with a 2.3-fold risk of dementia compared with not carrying an APOE ϵ4 allele (95% CI of HR 1.49-3.53; p = 0.0002), and having a favorable CVH showed a 0.45-fold lower risk of dementia (95% CI of HR 0.20-1.01; p = 0.0527) compared to having an unfavorable CVH when all 3 components were included in the model. We did not observe an interaction between CVH and GRS (p = 0.99) or APOE ϵ4 (p = 0.16). Conclusions:We observed that both genetic risk and CVH contribute additively to dementia risk.

Original languageEnglish (US)
Pages (from-to)E1341-E1350
Issue number10
StatePublished - Sep 8 2020

ASJC Scopus subject areas

  • Clinical Neurology


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