Limited evidence for heart rate variability as a predictor of cognitive and pathophysiological brain markers

BackgroundHeart rate variability (HRV) is related to cognitive functioning and may serve as an early Alzheimer's disease biomarker.ObjectiveWe examine whether HRV predicts cognitive and pathophysiological brain markers assessed eight and thirteen years later, independently of coronary calcification.Methods269 cognitively unimpaired adults were selected based on their coronary artery calcification score (absent, score=0; high, score≥300), obtained from cardiac computed tomography scans (T2, 2017-2022). HRV in the time domain (root mean square of successive RR interval differences), measured at T0 (2007-2013), T1 (2014-2017), and the change between T0 and T1, was the predictor. Outcomes included cognitive measures, serum Alzheimer's disease biomarkers, and brain imaging markers obtained at T3 (2022-2023). Linear regression models were run, stratified by coronary calcification groups and adjusted for demographics, lifestyle and cardiometabolic factors.ResultsParticipants with high T2 calcification showed lower HRV at T0 and a positive change compared to those with absent calcification. In participants with high T2 calcification, higher HRV at T0 was associated with lower Aβ₄₂/Aβ₄₀ at T3, while associations with all other markers were not significant. HRV at T1 and the change were not associated with any of the outcomes.ConclusionsHRV was not associated with cognitive and brain imaging outcomes. In participants with high calcification, higher HRV measured thirteen-year earlier, typically a marker of a healthier state, was associated with a lower Aβ₄₂/Aβ₄₀ ratio, typically linked to Alzheimer's disease. Findings underscore the need to consider coronary calcification in research of HRV as a marker of cognitive decline.