Alzheimer’s disease and related dementias (ADRD) are debilitating conditions. They can be devastating, and many of the ADRD symptoms are considered irreversible. Determining modifiable risk factors and identifying people at higher risks for ADRD in earlier life are urgently needed. Circadian rhythms, operating over a near 24-h cycle, regulate biological and physiological processes. Circadian rhythms change markedly as people age, and the changes may in turn accelerate the aging effects. Patients with ADRD experience more pronounced forms of circadian disturbances than typical age-related alterations. Neurofunctional changes in the central pacemaker (i.e., suprachiasmatic nucleus, or SCN) have been demonstrated in AD patients, suggesting that the circadian network is vulnerable to AD pathology.

Prior human studies show that Aβ42 has a circadian pattern which is ablated in people with AD. Perturbed rest-activity rhythms (RARs) predicted future incident AD in older adults without dementia. Shift work that disrupts circadian rhythms has also been associated with higher risks for dementia. Moreover, dampened or more fragmented RARs were also associated with amyloid pathology in cognitively intact older adults.

Circadian regulation, autonomic function, and Alzheimer’s disease

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• Project period: 2020-2023

Circadian or ~24-hour day-night rhythm is a fundamental aspect in physiology that might be involved in the process of Alzheimer’s disease (AD). Autonomic function, a largely unconscious regulator controlling a wide range of bodily functions, is another node that may play a role in the neurodegenerative process, and may explain the link between circadian regulation and AD. This study is designed to formally confirm these two questions by investigating an elderly cohort with motor activity and pulse rate monitored annually, and with health followed for up to 15 years. Results from this project may provide new intervention targets in future clinical studies of AD, and can lay the groundwork for the design of novel unobtrusive, cost-efficient tools for long-term monitoring of cognitive impairment or risk for AD.

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