The Relationship Between Disrupted Circadian Rhythms and Alzheimer’s Biomarker Changes

Recent research has shown a potential link between disrupted circadian rhythms in cognitively normal adults and higher subsequent amyloid-beta levels. This relationship has been reported to be even stronger in APOE4 carriers. The findings from a prospective study indicated that higher daily variability at baseline, which is an indicator of fragmented 24-hour activity rhythms, was associated with higher PET amyloid burden 8 years later. These findings are significant as they shed light on a potential risk factor for Alzheimer’s disease pathology.

The study conducted by Julia Neitzel, PhD, of Erasmus University Medical Center and her colleagues, found that the relationship between disrupted circadian rhythms and higher amyloid-beta levels remained consistent even after excluding participants with baseline Alzheimer’s pathology. This suggests that fragmented 24-hour activity rhythms may indeed be a risk factor for Alzheimer’s disease rather than a result of the pathology itself. The study’s findings challenge existing literature on Alzheimer’s disease and sleep, highlighting the importance of controlling for Alzheimer’s disease pathology at baseline when investigating this relationship.

According to the Lancet Commission, modifying key risk factors could prevent or delay up to 40% of dementia cases. However, sleep is not currently included as one of these factors. The role of sleep dysfunction in the development of Alzheimer’s disease and dementia remains unclear. Researchers like Matthew Pase from Monash University suggest that improving sleep symptomatology could be a strategy to lower dementia risk. The study’s findings support the idea that circadian disruption may indeed increase dementia risk, especially when looking at Alzheimer’s biomarker changes that occur years before dementia onset.

The analysis conducted by Neitzel and her team involved evaluating sleep and 24-hour activity rhythms from 319 participants in the Rotterdam study. All participants were cognitively normal and had no dementia diagnosis at baseline. Objective sleep and 24-hour activity rhythms were assessed using actigraphy for 7 days and nights, along with self-reported sleep patterns. Plasma assays were used to measure baseline amyloid-beta levels and phosphorylated tau levels.

While higher fragmentation of 24-hour activity rhythms was associated with more severe amyloid pathology at follow-up, other objective or self-reported measures of sleep did not show the same association. Surprisingly, there was no strong relationship between sleep duration and amyloid pathology, contradicting some earlier research findings. The study’s emphasis on objective measures of sleep and activity rhythms provides valuable insights into the potential risk factors for Alzheimer’s disease.

As with any study, there are limitations to consider. The researchers noted that the study’s sample size was relatively small, which could impact the generalizability of the findings. Additionally, because participants only had one PET scan, longitudinal analyses were limited. Moving forward, research in this area could benefit from larger sample sizes, as well as the inclusion of more objective measures of sleep, such as polysomnography. Future studies could also explore the impact of factors like sleep apnea on Alzheimer’s biomarker changes.

The relationship between disrupted circadian rhythms and Alzheimer’s biomarker changes appears to be a significant area of interest in dementia research. By understanding how sleep and circadian rhythms influence disease pathology, researchers and clinicians may be able to develop innovative strategies for preventing or delaying the onset of dementia. More work is needed to fully elucidate the complex interplay between sleep, circadian rhythms, and Alzheimer’s disease.