Impaired baroreflex sensitivity and long‐term risk of dementia in community‐based older adults

Abstract Background Hypertension is an important modifiable risk factor for dementia, but the role of blood pressure (BP) in the development of dementia is not fully understood. Emerging data links increased BP variability and abnormal BP dynamics to dementia risk, but the relationship between baroreflex sensitivity (BRS), a fundamental physiological mechanism for maintaining stable BP, and dementia risk is unknown. Methods We investigated the association of BRS with the risk of dementia in community‐based older adults from the Rotterdam Study in the Netherlands. We determined cardiac BRS using a 5‐minute continuous beat‐to‐beat recording of BP and heart rate measured in a supine position between 1997 and 1999 and ascertained incident dementia cases using a standardized protocol from baseline through January 1, 2020. We quantified the association of cardiac BRS with dementia risk using adjusted cause‐specific hazard ratios. Results Of 1,819 participants (63% women; mean [SD] age, 71.0 [6.3] years), 421 developed dementia during a median follow‐up of 14.8 years. The association of cardiac BRS with dementia risk differed by antihypertensive medication use ( P for interaction = 0.03) and was only observed in participants not taking antihypertensive medication. Specifically, reduced BRS was associated with a higher risk of dementia (cause‐specific hazard ratio [HR] comparing bottom versus top quintiles: 1.62; 95% confidence interval [CI]: 1.08‐2.42, P for trend = 0.02) and all‐cause mortality (corresponding HR: 1.77; 95%CI: 1.33‐2.37, P for trend<0.001) after adjusting for age, sex, APOE genotype, and traditional vascular risk factors. The association remained after additional adjustment for sitting BP level and beat‐to‐beat BP variability. Conclusions Among older adults not taking antihypertensive medication, reduced cardiac BRS was associated with a higher long‐term risk of dementia and all‐cause death over 23 years. Impaired BRS may be a novel biomarker of significant clinical relevance for early detection and prevention of dementia in older adults.