Abstract
BACKGROUND: Increased blood pressure (BP) variability is linked to dementia risk, but the relationship between baroreflex sensitivity (BRS), a fundamental mechanism for maintaining stable BP, and dementia risk is undetermined. METHODS: We tested the hypothesis that impaired BRS is associated with increased dementia risk in 1819 older adults (63% women; age, 71.0±6.3 years) from the community-based Rotterdam Study. Cardiac BRS was determined from a 5-minute beat-to-beat BP recording at supine rest between 1997 and 1999. Cardiac BRS measures the correlation between changes in consecutive beat-to-beat systolic BP and subsequent responses in heartbeat intervals, with a higher value indicating better BRS. The primary outcome was incident dementia ascertained from baseline through January 1, 2020; the secondary outcome was all-cause mortality. RESULTS: During a median follow-up of 14.8 years, 421 participants developed dementia. The association of cardiac BRS with dementia risk differed by antihypertensive medication use (P(interaction)=0.03) and was only observed in participants not taking antihypertensives. Specifically, in those not taking antihypertensive medication, reduced BRS was associated with a higher risk of dementia (adjusted hazard ratio comparing bottom versus top quintiles, 1.60 [95% CI, 1.07-2.40]; P(trend)=0.02). Reduced BRS was also associated with an increased risk of death (corresponding hazard ratio, 1.76 [95% CI, 1.32-2.35]). The association remained after adjusting for average BP and BP variability. CONCLUSIONS: Impaired BRS partly explains hypertension-related brain damage and excessive dementia risk beyond conventional BP measures, making it a potential novel biomarker for the early detection and prevention of dementia.