PT - JOURNAL ARTICLE AU - Peloso, Gina M. AU - Beiser, Alexa S. AU - Satizabal, Claudia L. AU - Xanthakis, Vanessa AU - Vasan, Ramachandran S. AU - Pase, Matthew P. AU - Destefano, Anita L. AU - Seshadri, Sudha TI - Cardiovascular health, genetic risk, and risk of dementia in the Framingham Heart Study AID - 10.1212/WNL.0000000000010306 DP - 2020 Sep 08 TA - Neurology PG - e1341--e1350 VI - 95 IP - 10 4099 - http://n.neurology.org/content/95/10/e1341.short 4100 - http://n.neurology.org/content/95/10/e1341.full SO - Neurology2020 Sep 08; 95 AB - 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.AD=Alzheimer disease; AHA=American Heart Association; CI=confidence interval; CVH=cardiovascular health; DSM-IV=Diagnostic and Statistical Manual of Mental Disorders, 4th edition; FHS=Framingham Heart Study; GRS=genetic risk score; HR=hazard ratio; MMSE=Mini-Mental State Examination; SNP=single nucleotide polymorphism