Body clock disruptions may indicate early-stage Alzheimer's

Disruption of the internal body clock is commonly associated in people with Alzheimer’s disease and may lead to further development of the disorder. New research suggests circadian rhythm abnormalities occur earlier in people who don’t have Alzheimer’s disease, but whose brain scans may show early risk of developing the disease.

“Ultimately, circadian dysfunction is a major source of morbidity for patients with Alzheimer’s and their caretakers and one of the major causes of institutionalization,” wrote corresponding author Yo-El S. Ju, MD, in the department of neurology at Washington University School of Medicine in St. Louis. “Thus, circadian dysfunction in Alzheimer’s disease is a serious but poorly understood phenomenon.”

The study published online January 29 in JAMA Neurology, may help doctors identify those at risk much earlier than previously thought.

Researchers conducted circadian rhythm analysis in 189 participants, with an average age of 66, who volunteered for Washington University’s Knight Alzheimer’s Disease Research Center. They were given a PET scan to detect amyloid plaques in the brain, a cerebrospinal fluid test for Alzheimer’s-related proteins or a combination of the two.

Out of all participants, 139 had no sign of amyloid proteins associated with preclinical Alzheimer’s, though several had circadian disruptions that were linked to advanced age, sleep apnea or other causes.

Among the remaining 50 involved in the study, with either brain scans or cerebrospinal fluid indicating an abnormality, all experienced significant disruptions in their internal body clocks, determined by amount of rest achieved and activity during the day.

The 24-hour activity monitoring allowed researchers to find participants who experienced fragmented periods of activity during the day and disrupted sleep at night. It was found those in that group were more likely to show evidence of amyloid buildup in their brains.

Researchers also conducted a separate study in mice that showed similar circadian disruptions accelerate the development of amyloid plaques in the brain. That study is set to be published Jan. 30 in The Journal of Experimental Medicine, according to a Washington University School of Medicine in St. Louis press release.

"At the very least, these disruptions in circadian rhythms may serve as a biomarker for preclinical disease," said Ju in the same release. "We want to bring back these subjects in the future to learn more about whether their sleep and circadian rhythm problems lead to increased Alzheimer's risk or whether the Alzheimer's disease brain changes cause sleep/wake cycle and circadian problems."