Circadian regulation, autonomic function, and Alzheimer’s disease

Peng Li, PhD
Brigham and Women's Hospital (Boston, MA)
Year Awarded:
2020
Grant Duration:
September 1, 2020 to August 31, 2023
Disease:
Alzheimer's Disease
Award Amount:
$285,000
Grant Reference ID:
A2020886S
Award Type:
Standard
Award Region:
US Northeastern
Peng Li, PhD

Circadian regulation, autonomic function, and Alzheimer’s disease

Summary

Cure for Alzheimer’s disease is still lacking. It is important to identify the risk factors for the disease and its multiple impacts on body functions in order to prevent or slow down the progression of the disease and treat related symptoms. Using novel non-invasive assessment of circadian regulation and autonomic function by wearable technology, this project is designed to determine whether changes in these two important physiological functions can predict the development and progression of Alzheimer’s disease and cognitive decline in the elderly people at early, preclinical stages. This project may potentially provide new intervention targets in future clinical studies of Alzheimer’s disease, and can lay the groundwork for the design of novel unobtrusive, cost-efficient tools for long-term monitoring of cognitive impairment or risk for Alzheimer’s disease.

Details

The 2017 Nobel Prize in Physiology or Medicine was awarded to three scientists for their discoveries of molecular mechanisms of the inner biological clock in humans and other living organism on earth that generates circadian rhythm and helps us anticipate and adapt to the 24-h day-night cycle. Does the dysfunction of the circadian clock increase the risk of developing Alzheimer’s disease (AD) and accelerate its progression? If so, is the effect through the impact of clock dysfunction on the autonomic nervous system — a control system that acts largely unconsciously and regulates bodily functions such as heart rate and blood supply to the brain, and is primarily responsible for the “fight-or-flight” response? We are following over 1,000 elderly individuals for many years from the time when they are cognitively normal to death. We assess the functional changes of the clock and the autonomic nervous system each year, examine whether these changes predict future development of cognitive decline and AD, and compare the change rates across different AD stages from no cognitive impairment to mild cognitive impairment, and to dementia. Our proposed novel nonlinear analytical tools are based on spontaneous fluctuations in daily motor activity and overnight heart rate recordings. The tools, together with the longitudinal study design, allow us to assess unobtrusively changes in the circadian clock and the autonomic nervous system over time, and to illustrate their contributions to the development of AD and related symptoms in the elderly. The results will potentially establish circadian clock dysfunction as a risk factor for Alzheimer’s disease, will put forward a potential pathological pathway—autonomic dysfunction—for the neurogenerative process of AD. A cure for AD is still lacking. The results to be obtained may potentially provide new targets, namely circadian and autonomic functions, for prevention of AD, for better therapies/treatments of other complications in AD such as depression, dizziness, syncope, and falls that are related to autonomic dysfunction, and for better outcomes in the elderly (i.e., morbidity, institutionalization, and death). Our study can also lay the groundwork for the design of novel unobtrusive, cost-efficient tools for long-term monitoring of cognitive impairment or risk for AD, and will further highlight the importance of circadian health that will encourage people to maintain regular daily schedules including sleep/wake in order to reduce AD risk and promote health aging.

About the Researcher

Dr. Peng Li's multidisciplinary research in biomedical science covers physiological data processing, sleep/circadian physiology, and human aging and age-related neurodegenerations. He received his PhD in Biomedical Engineering in 2014 from Shandong University, China, and obtained his postdoctoral trainings first in nonlinear dynamics of physiology at Shandong University (2014-2015), then in sleep/circadian physiology and neurophysiology at the Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital (BWH), Harvard Medical School (HMS) (2016-2018). In 2019, Dr. Li was promoted to an Instructor in Medicine at HMS and Associate Physiologist at BWH. Since joining the Division, he has been a Project Leader for three NIH-funded R01/RF1 projects, focusing on the understanding of the impacts of Alzheimer’s disease on behavior and physiology and the development of biomarkers for better prediction of AD. Serving as the Research Director of Medical Biodynamics Program at BWH, Dr. Li’s current work is focused on harnessing the power of ambulatory data, understanding the sleep/circadian regulation, autonomic function, and sedentary life-style factors such as daytime napping in AD process, and promoting proactive healthcare technology. As a researcher at the interface of engineering and medicine, Dr. Li is well positioned to advance the understanding of functional physiological changes in the pathogenesis of AD.

Personal Story

I believe that managing our health proactively is as important as our quest to cure. Growing up in the rural heartlands of Northern China, most worried about the next harvest more than their health status until the devastation of previously “hidden” symptoms arose; and none were more devastating than that of heart and brain diseases. These diseases care not where one is from, or what race we belong to. Many passed away suddenly before their families ever knew what had happened. In choosing my college major, I wanted to best prepare myself to make a positive impact on these families. The choice of biomedical engineering, by luck, or fate, immersed me in a unique discipline to tackle human disease with the rigor of an engineer. During my PhD, I became fascinated by unobtrusive, noninvasive approaches to assessing cardiovascular function prior to development of cardiovascular symptoms. What continues to intrigue me is whether everyday changes in our innate bodily functions we take for granted, can be assessed and tracked reliably from physiological recordings at rest. I was fascinated by the complex patterns in the spontaneous fluctuations of physiological output such as ECG, pulse wave, and heart sound. By adopting nonlinear dynamic concept of complexity and applying complexity analysis to these physiological signals, my colleagues and I designed a new medical equipment for noninvasive assessments of cardiac autonomic function, systolic function, and arterial function that has been used in hospitals and primary care facilities across many provinces in China. Such research experience has driven my persistent interest in expanding my gained expertise to clinical medicine, especially in the ambulatory monitoring of the elderlies for aging related consequences. And my pursuit of proactive health continues as I learned that the complex nature of physiological output seems to find an origination in the brain. I joined the Medical Biodynamics Program at BWH and HMS for my postdoc training which has formally introduced me to the field of Alzheimer’s disease. I am keen to apply my gained expertise to promote a proactive strategy for early detection of individuals with elevated AD risk. It is my hope that my research will shed new light on whether these noncognitive physiological changes will contribute to the development of AD and will ultimately integrate our findings to advance healthcare wearables. The generous support of BrightFocus and its donors will not only enable me to achieve our dreams but also serves as a catalyst to speed up our endeavors.

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