Circadian rhythm disruptions common to Alzheimer’s disease occur before memory loss and other symptoms in people whose memories are intact but whose brain scans show early, preclinical evidence of the condition, according to new research.
The findings, reported in JAMA Neurology, potentially could help doctors identify people at risk of Alzheimer’s earlier than currently is possible. That’s important because Alzheimer’s damage can take root in the brain 15 to 20 years before clinical symptoms appear.
“It wasn’t that the people in the study were sleep-deprived,” says first author Erik S. Musiek, assistant professor of neurology at the Washington University School of Medicine in St. Louis. “But their sleep tended to be fragmented. Sleeping for eight hours at night is very different from getting eight hours of sleep in one-hour increments during daytime naps.”
The researchers also conducted a separate study in mice, which appears in the Journal of Experimental Medicine, showing that similar circadian disruptions accelerate the development of amyloid plaques in the brain, which are linked to Alzheimer’s.
Previous studies, conducted in people and in animals, have found that levels of amyloid fluctuate in predictable ways during the day and night. Amyloid levels decrease during sleep, and several studies have shown that levels increase when sleep is disrupted or when people don’t get enough deep sleep, according to research by senior author Yo-El Ju.
“In this new study, we found that people with preclinical Alzheimer’s disease had more fragmentation in their circadian activity patterns, with more periods of inactivity or sleep during the day and more periods of activity at night,” says Ju, an assistant professor of neurology.
The researchers tracked circadian rhythms in 189 cognitively normal, older adults with an average age of 66. Some had positron emission tomography (PET) scans to look for Alzheimer’s-related amyloid plaques in their brains. Others had their cerebrospinal fluid tested for Alzheimer’s-related proteins. And some had both scans and spinal fluid testing.
Of the participants, 139 had no evidence of the amyloid protein that signifies preclinical Alzheimer’s. Most had normal sleep/wake cycles, although several had circadian disruptions that were linked to advanced age, sleep apnea, or other causes.
But among the other 50 subjects—who either had abnormal brain scans or abnormal cerebrospinal fluid—all experienced significant disruptions in their internal body clocks, determined by how much rest they got at night and how active they were during the day. Disruptions in the sleep/wake cycle remained even after the researchers statistically controlled for sleep apnea, age, and other factors.
The study subjects all wore devices similar to exercise trackers for one to two weeks. Each also completed a detailed sleep diary every morning.
By tracking activity during the day and night, the researchers could tell how scattered rest and activity were throughout 24-hour periods. Subjects who experienced short spurts of activity and rest during the day and night were more likely to have evidence of amyloid buildup in their brains.
