In the Journals

Circadian rhythm abnormalities present in preclinical Alzheimer’s disease

Erik S. Musiek

Research published in JAMA Neurology demonstrated that preclinical Alzheimer’s disease and aging were independently associated with circadian rhythm abnormalities.

“Circadian dysfunction in [Alzheimer’s disease] is a serious but poorly understood phenomenon. Ultimately, circadian dysfunction is a major source of morbidity for patients with [Alzheimer’s disease] and their caretakers and [one] of the major causes of institutionalization,” Erik S. Musiek, MD, PhD, assistant professor of neurology, Washington University School of Medicine, and from the Knight Alzheimer’s Disease Research Center, and colleagues wrote. “To our knowledge, only a single study has examined patients with mild cognitive impairment, and no previous studies have described circadian function in preclinical [Alzheimer’s disease].”

In a cross-sectional study, researchers examined the relationship between circadian function, aging and preclinical Alzheimer’s disease pathology in 189 cognitively normal older adults. Participants underwent 1 to 2 weeks of actigraphy between 2010 and 2012, after which the investigators conducted circadian rhythm analysis on actigraphy data collected 3 years before to 6 months after using cosinor, nonparametric and empirical mode decomposition. Musiek and colleagues also conducted longitudinal clinical assessment, amyloid imaging with Pittsburgh Compound B (PiB) and cerebrospinal fluid biomarker collection to examine preclinical Alzheimer’s.

Alzheimer’s disease and aging were independently associated with circadian rhythm abnormalities, according to research findings.
Source: Shutterstock.com

The researchers found that instabilities in circadian rhythm were present in preclinical Alzheimer’s disease, even after adjusting for effects of aging and sex. The results showed that in the absence of amyloid pathology, older age (P = .003) and male sex (P = .04), were linked with a significant increase in circadian rhythm fragmentation. Increasing age was also associated with decreased circadian amplitude by all measures (P = .003) and increased fragmentation by IV (P = .003). After adjusting for age, female sex was associated with higher amplitude, less fragmentation and more robustness, demonstrating that age and sex effect circadian function in the absence of preclinical amyloid pathology. In addition, PiB+ participants experienced significantly more circadian fragmentation as measured by IV (P = .05) after adjusting for age and sex. Notably, the researchers found that there was no relationship between sleep efficiency and any circadian variables.

“Circadian rhythm dysfunction is happening early in the course of Alzheimer’s disease, not just in people with advanced [Alzheimer’s disease],” Musiek told Healio Psychiatry. “Promoting good ‘circadian hygiene,’ such as avoiding excessive light at night, keeping consistent bed times, and getting plenty of outdoor light exposure and physical activity during the day may be generally good for the brain by supporting strong circadian function.” – by Savannah Demko

Disclosures: Musiek reports consulting for Eisai Pharmaceuticals. Please see the study for all other authors’ relevant financial disclosures.

Erik S. Musiek

Research published in JAMA Neurology demonstrated that preclinical Alzheimer’s disease and aging were independently associated with circadian rhythm abnormalities.

“Circadian dysfunction in [Alzheimer’s disease] is a serious but poorly understood phenomenon. Ultimately, circadian dysfunction is a major source of morbidity for patients with [Alzheimer’s disease] and their caretakers and [one] of the major causes of institutionalization,” Erik S. Musiek, MD, PhD, assistant professor of neurology, Washington University School of Medicine, and from the Knight Alzheimer’s Disease Research Center, and colleagues wrote. “To our knowledge, only a single study has examined patients with mild cognitive impairment, and no previous studies have described circadian function in preclinical [Alzheimer’s disease].”

In a cross-sectional study, researchers examined the relationship between circadian function, aging and preclinical Alzheimer’s disease pathology in 189 cognitively normal older adults. Participants underwent 1 to 2 weeks of actigraphy between 2010 and 2012, after which the investigators conducted circadian rhythm analysis on actigraphy data collected 3 years before to 6 months after using cosinor, nonparametric and empirical mode decomposition. Musiek and colleagues also conducted longitudinal clinical assessment, amyloid imaging with Pittsburgh Compound B (PiB) and cerebrospinal fluid biomarker collection to examine preclinical Alzheimer’s.

Alzheimer’s disease and aging were independently associated with circadian rhythm abnormalities, according to research findings.
Source: Shutterstock.com

The researchers found that instabilities in circadian rhythm were present in preclinical Alzheimer’s disease, even after adjusting for effects of aging and sex. The results showed that in the absence of amyloid pathology, older age (P = .003) and male sex (P = .04), were linked with a significant increase in circadian rhythm fragmentation. Increasing age was also associated with decreased circadian amplitude by all measures (P = .003) and increased fragmentation by IV (P = .003). After adjusting for age, female sex was associated with higher amplitude, less fragmentation and more robustness, demonstrating that age and sex effect circadian function in the absence of preclinical amyloid pathology. In addition, PiB+ participants experienced significantly more circadian fragmentation as measured by IV (P = .05) after adjusting for age and sex. Notably, the researchers found that there was no relationship between sleep efficiency and any circadian variables.

“Circadian rhythm dysfunction is happening early in the course of Alzheimer’s disease, not just in people with advanced [Alzheimer’s disease],” Musiek told Healio Psychiatry. “Promoting good ‘circadian hygiene,’ such as avoiding excessive light at night, keeping consistent bed times, and getting plenty of outdoor light exposure and physical activity during the day may be generally good for the brain by supporting strong circadian function.” – by Savannah Demko

Disclosures: Musiek reports consulting for Eisai Pharmaceuticals. Please see the study for all other authors’ relevant financial disclosures.