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

BACKGROUND: In 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-ß (Aß) in healthy younger and older adults. In healthy adults, higher plasma Aß 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 Aß. Our secondary objectives are to examine the effects of daily slow-paced breathing on brain structure and the rate of learning. METHODS: Adults 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 Aß40 and Aß42 levels and plasma Aß42/40 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 Aß42. Recruitment began in January 2023. Interventions are ongoing and will be completed by the end of 2023. DISCUSSION: Our HRV-ER trial was groundbreaking in demonstrating that a behavioral intervention can reduce plasma Aß 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.

Diminished pre-stimulus alpha-lateralization suggests compromised self-initiated attentional control of auditory processing in old age.

Older adults experience difficulties in daily situations that require flexible information selection in the presence of multiple competing sensory inputs, like for instance multi-talker situations. Modulations of rhythmic neural activity in the alpha-beta (8-30 Hz) frequency range in posterior brain areas have been established as a cross-modal neural correlate of selective attention. However, research linking compromised auditory selective attention to changes in rhythmic neural activity in aging is sparse. We tested younger (n = 25; 22-35 years) and older adults (n = 26; 63-76 years) in an attention modulated dichotic listening task. In this, two streams of highly similar auditory input were simultaneously presented to participants' both ears (i.e., dichotically) while attention had to be focused on the input to only one ear (i.e. target) and the other, distracting information had to be ignored. We here demonstrate a link between severely compromised auditory selective attention in aging and a partial reorganization of attention-related rhythmic neural responses. In particular, in old age we observed a shift from a self-initiated, preparatory modulation of lateralized alpha rhythmic activity to an externally driven response in the alpha-beta range. Critically, moment-to-moment fluctuations in the age-specific patterns of self-initiated and externally driven lateralized rhythmic activity were associated with behavioral performance. We conclude that adult age differences in spatial selective attention likely derive from a functional reorganization of rhythmic neural activity within the aging brain.