Alzheimer disease

Alzheimer Disease May Be Foreshadowed by Circadian Dysfunction

Circadian dysfunction is associated with the presence of preclinical Alzheimer disease (AD) and may serve as a biomarker of preclinical disease, a new study found.

For their study, the researchers evaluated 205 cognitively normal participants at a single center from 2010 to 2012. During the study, participants underwent at-home actigraphy for 7 to 14 days, as well as clinical assessment, amyloid imaging with Pittsburgh Compound B (PiB), and cerebrospinal fluid biomarker collection.

Data from 3 years before to 6 months after actigraphy were evaluated in a circadian rhythm analysis via cosinor, nonparametric, and empirical mode decomposition methods.

Ultimately, the analysis included 189 participants (mean age 66.6 years) with complete available data. Study results revealed that, in the absence of amyloid pathology, older age and male sex were associated with a significant increase in intradaily variability and a decrease in amplitude by several measures.

Additionally, following adjustment for several factors, the presence of preclinical amyloid plaque pathology or increasing cerebrospinal fluid phosphorylated-tau to amyloid β 42 ratio was also found to be associated with increased intradaily variability.

“Preclinical AD is associated with rest-activity rhythm fragmentation, independent of age or sex,” the researchers concluded. “Aging was also associated with circadian dysfunction independently of preclinical AD pathology, particularly in men. The presence of circadian rhythm abnormalities in the preclinical phase of AD suggests that circadian dysfunction could contribute to early disease pathogenesis or serve as a biomarker of preclinical disease.”

—Christina Vogt


Musiek ES, Bhimasani M, Zangrilli MA, Morris JC, Holtzman DM, Ju YES. Circadian rest-activity pattern changes in aging and preclinical Alzheimer disease [Published online January 29, 2018]. JAMA Neurol. doi:10.1001/jamaneurol.2017.4719.