Abstract
BACKGROUND AND OBJECTIVES: Previous randomized controlled trials and longitudinal studies have indicated that ongoing antihypertensive use in late life reduces all-cause dementia risk, but the specific impact on Alzheimer dementia (AD) and non-AD risk remains unclear. This study investigates whether previous hypertension or antihypertensive use modifies AD or non-AD risk in late life and the ideal blood pressure (BP) for risk reduction in a diverse consortium of cohort studies. METHODS: This individual participant data meta-analysis included community-based longitudinal studies of aging from a preexisting consortium. The main outcomes were risk of developing AD and non-AD. The main exposures were hypertension history/antihypertensive use and baseline systolic BP/diastolic BP. Mixed-effects Cox proportional hazards models were used to assess risk and natural splines were applied to model the relationship between BP and the dementia outcomes. The main model controlled for age, age(2), sex, education, ethnoracial group, and study cohort. Supplementary analyses included a fully adjusted model, an analysis restricting to those with >5 years of follow-up and models that examined the moderating effect of age, sex, and ethnoracial group. RESULTS: There were 31,250 participants from 14 nations in the analysis (41% male) with a mean baseline age of 72 (SD 7.5, range 60-110) years. Participants with untreated hypertension had a 36% (hazard ratio [HR] 1.36, 95% CI 1.01-1.83, p = 0.0406) and 42% (HR 1.42, 95% CI 1.08-1.87, p = 0.0135) increased risk of AD compared with "healthy controls" and those with treated hypertension, respectively. Compared with "healthy controls" both those with treated (HR 1.29, 95% CI 1.03-1.60, p = 0.0267) and untreated hypertension (HR 1.69, 95% CI 1.19-2.40, p = 0.0032) had greater non-AD risk, but there was no difference between the treated and untreated groups. Baseline diastolic BP had a significant U-shaped relationship (p = 0.0227) with non-AD risk in an analysis restricted to those with 5-year follow-up, but otherwise there was no significant relationship between baseline BP and either AD or non-AD risk. DISCUSSION: Antihypertensive use was associated with decreased AD but not non-AD risk throughout late life. This suggests that treating hypertension throughout late life continues to be crucial in AD risk mitigation. A single measure of BP was not associated with AD risk, but DBP may have a U-shaped relationship with non-AD risk over longer periods in late life.