2023 Alzheimer's Association Clinician Scientist Fellowship (AACSF)
Sleep/circadian Regulation and Progression to Postoperative Dementia
How are individuals with altered sleep at greater risk for reduced brain function and dementia after surgery?
Lei Gao, Ph.D.
Massachusetts General Hospital
Boston, MA - United States
Background
As people age, they are more likely to undergo various surgeries, which can promote health risks in some older adults. Such risks include delirium, or the temporary disruption of cognitive ability (brain function) that results in confusion and decreased awareness of one’s environment. Postoperative cognitive problems may also increase an older adult’s risk for Alzheimer’s and other dementia. Moreover, though scientists do not yet understand why certain older individuals experience health risks after surgery, current research suggests that changes in sleep patterns may be involved.
In initial studies, Dr. Lei Gao and colleagues found that individuals with disrupted circadian rhythms before surgery have a greater risk for postoperative delirium and dementia. Circadian rhythms are natural biological changes that occur over an approximately twenty-four hour cycle. These rhythms usually respond to the amount of light and darkness in an environment, and involve daily patterns of sleeping, eating and other activities. The researchers also found that abnormal circadian rhythms may be linked to specific Alzheimer’s-related changes. Such changes include abnormal levels of tau and beta-amyloid protein in the blood and cerebrospinal fluid (CSF, the biological fluid surrounding the brain and spinal cord), and the presence of APOE-e4, a gene variation that may promote Alzheimer’s risk in some populations.
Research Plan
Dr. Gao and colleagues will examine how altered sleep promotes cognitive problems and dementia risk after surgery. They will recruit around 550 older individuals who are enrolled in a large study of aging and who recently underwent surgery. They will be asked to prepare sleep diaries and wear sleep monitoring devices to help the researchers track their sleep patterns over time. Using this tracking information, along with results from cognitive, genetic and blood tests, Dr. Gao’s team will determine how preoperative sleep disturbances are related to one’s risk for postoperative delirium and dementia – and the role that APOE-e4 and abnormal tau levels in the blood may play in these relationships.
Impact
Dr. Gao’s study could help clarify the biological mechanisms underlying post-operative brain changes in older adults. It could also lead to novel sleep-related strategies for preventing such changes.