U-shaped association of resting heart rate with cognitive decline.

Reports of associations between bradycardia and elevated resting heart rate with cognitive decline are inconsistent, and the underlying mechanisms unclear. Resting heart rate was recorded in a prospective cohort of memory clinic subjects, and the associations of resting heart rate with cross-sectional cognition, brain magnetic resonance imaging and circulating biomarkers (pTau-181 and neurofilament light chain), and longitudinal cognitive decline were investigated. Subjects with atrial fibrillation were excluded. Among 643 subjects (mean age 72.8 ± 8.0 years, 57% female, 39% dementia), 35% had resting heart rate between 60 and 69 bpm, 23% had bradycardia (<60 bpm) and 42% had elevated resting heart rate (≥70 bpm). Compared to 60-69 bpm, both bradycardia (<60 bpm) and elevated resting heart rate ≥70 bpm were associated with worse baseline global cognition (P < 0.05), and elevated resting heart rate additionally with worse Clinical Dementia Rating-Sum of boxes scores (P < 0.05) and executive function on multivariable adjustment (P = 0.001). Longitudinally, resting heart rate ≥70 bpm was associated with accelerated global cognitive decline, and bradycardia with accelerated functional decline (P interaction < 0.05). Regarding neuroimaging and circulating biomarkers, bradycardia was associated with reduced grey matter volume, and higher levels of circulating pTau-181 and neurofilament light chain when compared to resting heart rate 60-69 bpm (P < 0.05). Conversely, elevated resting heart rate ≥70 bpm was associated with higher burden of cortical infarcts, cerebral microbleeds and lacunes compared to resting heart rate 60-69 bpm, and higher white matter hyperintensity volume ratio and cerebral microbleeds compared to bradycardia (P < 0.05). Resting heart rate displayed a U-shaped association with cognitive impairment and structural cerebral abnormalities, and may be underpinned by distinct mechanisms. Further study of the mechanisms underlying resting heart rate and cognitive trajectories are warranted. Trial registration: National Healthcare Group Domain Specific Review Board 2018/01098 and 2010/00017.