Practicing paced breathing exercises appears to have an impact on the levels of peptides associated with Alzheimer’s disease, according to new research published in Scientific Reports. The findings suggest that such interventions may have potential in modulating biomarkers related to the disease, although further research is needed to fully understand the underlying mechanisms and long-term effects.

“I was interested in whether inducing slow oscillations in heart rate during slow paced breathing would help increase clearance of amyloid beta from the brain,” said study author Mara Mather, a professor of gerontology, psychology, and biomedical engineering at the University of Southern California. “I hypothesized it could do so as the practice induces some of the features of deep sleep – slow physiological oscillations and low noradrenergic activity – that have been identified as promoting clearance of brain waste.”

As people age, parasympathetic activity declines, while sympathetic (or noradrenergic) activity increases. These age-related changes are associated with conditions related to Alzheimer’s disease like sleep disorders, diabetes, and heart disease.

The researchers believed that these age-related changes in sympathetic and parasympathetic activity might influence the levels of amyloid beta (Aβ) peptides in the brain and body. Increased neuronal or cellular activity is known to stimulate the release of amyloid beta. However, there had been limited research on how these physiological changes during aging might contribute to the factors that make someone susceptible to developing Alzheimer’s.

To investigate this further, the researchers conducted a study as part of a larger heart rate variability biofeedback intervention. They recruited healthy participants, both younger and older adults, who did not have serious medical conditions. The focus of the current report was on the 54 younger and 54 older adults who participated.

The study consisted of seven weekly visits, during which baseline measurements were taken in the first two visits, and post-intervention measures were taken in the last two visits. After the second baseline measurements, participants received biofeedback training and were given a laptop connected to an ear sensor that measured their heartbeats and displayed real-time heart rate biofeedback. Participants were instructed to practice their assigned intervention technique at home for five weeks.

During the study, the participants engaged in biofeedback exercises twice a day for 20 minutes each time. They wore a heart monitor on their ear, which was connected to a laptop provided by the researchers. One group of participants was instructed to think of calm things or listen to calm music while keeping an eye on their heart rate displayed on the laptop screen. They aimed to keep their heart rate as steady as possible while meditating.

The other group was instructed to pace their breathing in rhythm with a pacer on the laptop screen. They inhaled when the square rose and exhaled when the square dropped. They also monitored their heart rates, which rose during inhalation and dropped to baseline during exhalation. The goal for this group was to increase the breathing-induced oscillations in their heart rate.

Blood samples were collected during the first and sixth weeks of the study. The researchers specifically examined the plasma of participants from both groups to measure the levels of amyloid beta peptides, particularly amyloid beta 40 and 42.

Accumulation of amyloid beta in the brain is believed to trigger the development of Alzheimer’s disease. Higher levels of amyloid beta 40 and 42 in circulating blood in healthy adults without signs of brain amyloid accumulation have been associated with a greater risk of developing Alzheimer’s disease, as indicated by a meta-analysis.

The researchers found that the group that performed paced breathing exercises aimed at increasing heart rate oscillations showed a decrease in the levels of both amyloid beta 40 and 42, while the group that focused on calm thoughts aimed at reducing heart rate oscillations showed an increase in the levels of both peptides. When the data was analyzed for younger and older adults separately, the same pattern of results was observed.

The findings suggest that regularly practicing the breathing technique to increase the breathing-induced oscillations in their heart rate could help keep the levels of these substances low and potentially reduce the risk of Alzheimer’s disease. “Heart rate variability biofeedback can decrease levels of amyloid beta in blood,” Mather told PsyPost. “In healthy adults, lower blood levels of amyloid beta are associated with lower risk of getting Alzheimer’s disease later.”

The study suggests three possible ways in which controlling heart rate fluctuations could affect the levels of these substances: by reducing their production, by improving their clearance from the body, and by enhancing their clearance from the brain. However, it is still unclear which mechanism is primarily responsible for the observed effects.

“The large effect of the HRV biofeedback on overall levels of amyloid beta was unexpected,” Mather said. “Based on our original hypothesis that HRV biofeedback could affect brain clearance of amyloid, we were most interested in a plasma biomarker of brain clearance of amyloid (the Aβ42/40 ratio). This score did show a moderate (but not quite significant) improvement among older adults.”

“However, our findings of overall changes in plasma amyloid beta levels in both younger and older adults are unlikely to be due to changes in brain clearance. We need further studies to determine what is driving this effect, but it seems likely to be caused either by changes in peripheral production or clearance of amyloid beta.”

Peripheral production of amyloid beta refers to the generation of amyloid beta in tissues and organs outside of the brain. While the brain is the main source of amyloid beta production, studies have shown that other organs, such as the liver, kidneys, and blood vessels, can also produce amyloid beta to some extent.

Amyloid beta can be cleared from the body through various mechanisms, including filtration by the kidneys, degradation by enzymes, and transport across the blood-brain barrier. Efficient clearance of amyloid beta from peripheral tissues is important for maintaining its proper balance and preventing its accumulation in the brain.

“One key point here is that there is growing research (for instance from patients with kidney disease whose kidneys do not clear out as much of the amyloid beta circulating in blood) that higher peripheral levels of amyloid beta appear to be a risk for Alzheimer’s disease,” Mather told PsyPost. “So even if the heart rate variability biofeedback is having all of its action outside of the brain, it is likely to matter for the brain.”

The study, “Modulating heart rate oscillation affects plasma amyloid beta and tau levels in younger and older adults“, was authored by Jungwon Min, Jeremy Rouanet, Alessandra Cadete Martini, Kaoru Nashiro, Hyun Joo Yoo, Shai Porat, Christine Cho, Junxiang Wan, Steve W. Cole, Elizabeth Head, Daniel A. Nation, Julian F. Thayer, and Mara Mather.

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