Daily heart rate variability biofeedback practice sessions affect plasma Αβ40 and Αβ42 levels in healthy younger and older adults: A randomized clinical trial (N = 108)

Background Genetic mutations affecting β‐amyloid (Αβ) production suggest that decreasing Αβ levels in healthy adults could prevent AD. However, evidence for behavioral interventions that decrease Αβ levels is lacking. The current study examined whether heart rate variability (HRV) biofeedback affects plasma Αβ levels. This intervention involves breathing slowly at a pace that maximizes the amplitude of heart rate oscillations. During slow paced breathing, the vagus nerve receives strong signals from stretch receptors in blood vessels and the lungs. These afferent signals stimulate ascending vagus nerve signaling that activate ‘safety’ signaling pathways, suppressing stress and arousal pathways in the brain and body. Experiencing adversity increases production of Aβ and risk of AD. We hypothesized that, in healthy adults, daily sessions involving slow paced breathing during HRV biofeedback could decrease Aβ by suppressing these adversity‐related processes. Method Healthy adults (N = 54 age 18‐35; N = 54 age 55‐80) practiced HRV biofeedback daily for five weeks. They were randomized to use slow paced breathing and HRV biofeedback to increase heart rate oscillations (Osc+ condition) or to use personalized strategies and HRV biofeedback to try to decrease heart rate oscillations (Osc‐ condition). Pre‐ and post‐intervention plasma Aβ40 and Aβ42 levels were quantified blind to condition. Gene expression analysis of peripheral blood samples of the 54 younger adults using bioinformatics‐based analyses of genome‐wide RNA profiles examined activity of pro‐inflammatory, neuroendocrine, and antiviral transcription control pathways relevant to the conserved transcriptional response to adversity (CTRA). We predicted that reductions in the CTRA across the 5‐week trial would be associated with reduced plasma Aβ. Result Both younger and older adults showed significant differences between Osc+ and Osc‐ conditions in change in plasma Aβ40 and Aβ42 levels (Figure 1). The Osc+ condition decreased Αβ while the Osc‐ condition increased Αβ. Individual changes in plasma Aβ from pre‐ to post‐intervention were associated with changes in expression of the CTRA in the predicted direction. Conclusion HRV biofeedback affects plasma Aβ and these effects are associated with changes in expression of genes upregulated during adversity. Future longer‐term studies should test whether reducing plasma Αβ via the Osc+ intervention reduces risk of developing AD.