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Brain Communications

U-shaped association of resting heart rate with cognitive decline

  • October 21, 2025
  • Christopher Chen, et al., National University Singapore
Product:
CNS Disease Panel 120
Topic:
Neurology
Disease Area:
Cardiovascular, Dementia
Sample Type:
Plasma
Back to Publications​
  • October 21, 2025
  • Christopher Chen, et al., National University Singapore
Topic/Product:
CNS Disease Panel 120
Disease Area:
Cardiovascular, Dementia
Sample Type:
Plasma

Abstract

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 (Pinteraction < 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. 

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Authors & Affiliations

Eugene S. J. Tan¹², *Ming Ann Sim²³⁴, *Lucia Li³⁵, Anqi Toh³, Eddie J. Y. Chong³, Siew Pang Chan¹, Cheuk Ni Kan³, Xin Tong Tan³, Jiangbo Cui³⁶, Saima Hilal³⁶⁷, Joyce R. Chong³⁶, Mitchell K. P. Lai³⁶, Narayanaswamy Venketasubramanian⁸, Boon Yeow Tan⁹, A. Mark Richards¹²¹⁰, Lieng-Hsi Ling¹²†, and Christopher L. H. Chen³⁶†

¹ Department of Cardiology, National University Heart Centre, Singapore 119074, Singapore
² Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore
³ Memory Aging and Cognition Center, National University Health System, Singapore 117599, Singapore
⁴ Department of Intensive Care Medicine, Ng Teng Fong General Hospital, Singapore 609606, Singapore
⁵ School of Clinical Medicine, University of Cambridge, Cambridge CB2 0SP, United Kingdom
⁶ Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore
⁷ Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117549, Singapore
⁸ Raffles Neuroscience Centre, Singapore 118700, Singapore
⁹ St. Luke’s Hospital, Singapore 659674, Singapore
¹⁰ Christchurch Heart Institute, University of Otago, Christchurch 8011, New Zealand

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Steve Williams, MD, PhD

CSO

Dr. Willams serves as the company’s Chief Scientific Officer. He was previously Chief Medical Officer at Standard Biotools and at SomaLogic where he pioneered the discipline for discovery and validation of predictive, diagnostic and prognostic models using machine-learning applied to large-plex proteomics. 20 such tests were used for drug characterization, safety and efficacy when incorporated in clinical drug trials at Pharma/Biotech and 17 different multivariate tests were validated and translated into regulated healthcare uses. Prior to SomaLogic, Dr. Williams was at Pfizer in the UK and the USA as a clinical triallist in Translational Medicine, and subsequently as VP, Global Clinical Technology. He sat on the National Advisory Council for the National Institute of Biomedical Imaging and Bioengineering, the Executive Committee for the FNIH Biomarkers Consortium, and worked with FDA and PhRMA on developing evidentiary standards for biomarker qualification. Dr. William’s medical training was in London, at Charing Cross and Westminster Medical School, followed by a PhD in medicine/physiology at the same institution and training in Radiology at the University of Newcastle Upon Tyne. Steve is co-inventor on 26 proteomics patents and author/coauthor on multiple foundational proteomics manuscripts.

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Justin McAnear

CFO

Mr. McAnear serves as the company’s Chief Financial Officer. He brings over 25 years of operational and financial leadership experience across various sectors and was instrumental in taking 10x Genomics public in 2019, serving as its CFO for over five years. Mr. McAnear served for over 3 years as Tesla’s VP of Worldwide Finance and Operations, supporting landmark initiatives such as the Model X and Model 3 launches and Solar City acquisition.  He also held various roles at Apple and J&J earlier in his career and served as a naval officer and aviator for over 9 years.