Heart rate and breathing effects on attention and memory (HeartBEAM): study protocol for a randomized controlled trial in older adults

BackgroundIn healthy people, the "fight-or-flight" sympathetic system is counterbalanced by the "rest-and-digest" parasympathetic system. As we grow older, the parasympathetic system declines as the sympathetic system becomes hyperactive. In our prior heart rate variability biofeedback and emotion regulation (HRV-ER) clinical trial, we found that increasing parasympathetic activity through daily practice of slow-paced breathing significantly decreased plasma amyloid-beta (A beta) in healthy younger and older adults. In healthy adults, higher plasma A beta is associated with greater risk of Alzheimer's disease (AD). Our primary goal of this trial is to reproduce and extend our initial findings regarding effects of slow-paced breathing on A beta. Our secondary objectives are to examine the effects of daily slow-paced breathing on brain structure and the rate of learning.MethodsAdults aged 50-70 have been randomized to practice one of two breathing protocols twice daily for 9 weeks: (1) "slow-paced breathing condition" involving daily cognitive training followed by slow-paced breathing designed to maximize heart rate oscillations or (2) "random-paced breathing condition" involving daily cognitive training followed by random-paced breathing to avoid increasing heart rate oscillations. The primary outcomes are plasma A beta 40 and A beta 42 levels and plasma A beta 42/40 ratio. The secondary outcomes are brain perivascular space volume, hippocampal volume, and learning rates measured by cognitive training performance. Other pre-registered outcomes include plasma pTau-181/tTau ratio and urine A beta 42. Recruitment began in January 2023. Interventions are ongoing and will be completed by the end of 2023.DiscussionOur HRV-ER trial was groundbreaking in demonstrating that a behavioral intervention can reduce plasma A beta levels relative to a randomized control group. We aim to reproduce these findings while testing effects on brain clearance pathways and cognition.Trial registration ClinicalTrials.gov NCT05602220. Registered on January 12, 2023.