Hypertension, a dementia polygenic risk score, APOE genotype, and incident dementia

Abstract

Introduction There is inconsistent evidence on whether genetic risk for dementia modifies the association between hypertension and dementia. Methods In 198,965 dementia-free participants aged >= 60 years, Cox proportional-hazards models were used to investigate the association between hypertension and incident dementia. A polygenic risk score (PRS) based on 38 non-apolipoprotein E (APOE) single nucleotide polymorphisms and APOE epsilon 4 status were used to determine genetic risk for dementia. Results Over 15 years follow-up, 6270 participants developed dementia. Hypertension was associated with a 19% increased risk of dementia (hazard ratio = 1.19, 95% confidence interval 1.11-1.27). The associations remained similar when stratifying by genetic risk, with no evidence for multiplicative interaction by dementia PRS (P = 0.20) or APOE epsilon 4 status (P = 0.16). However, the risk difference between those with and without hypertension was larger among those at higher genetic risk. Discussion Hypertension was associated with an increased risk of dementia regardless of genetic risk for dementia.