Sleep, 24-Hour Activity Rhythms, and Subsequent Amyloid-β Pathology

Area of Science:

• Neuroscience
• Gerontology
• Sleep Medicine

Background:

• Sleep disturbances are prevalent in older adults and linked to Alzheimer disease (AD) pathology, specifically amyloid-beta (Aβ) deposition.
• Identifying specific sleep and 24-hour activity rhythm disruptions is crucial for effective AD prevention strategies.
• The role of the apolipoprotein E ε4 (APOE4) genotype in this relationship requires further investigation.

Purpose of the Study:

• To investigate the association between 24-hour activity rhythms and sleep patterns with Aβ deposition in non-demented adults.
• To determine if disrupted activity and sleep precede Aβ deposition.
• To assess the influence of the APOE4 genotype on these associations.

Main Methods:

• An observational cohort study utilizing data from the Rotterdam Study.
• Included 319 participants without dementia who underwent Aβ positron emission tomography (PET) and APOE genotyping.
• Assessed objective sleep and 24-hour activity rhythms via actigraphy, alongside self-reported sleep, plasma biomarkers, and Aβ PET burden over a mean follow-up of 7.8 years.

Main Results:

• Higher intradaily variability, indicating fragmented 24-hour activity rhythms, was associated with increased Aβ PET burden at follow-up.
• This association was significantly stronger in APOE4 carriers compared to non-carriers.
• No significant association was found between objective or self-reported sleep measures and Aβ deposition.

Conclusions:

• Fragmentation of 24-hour activity rhythms is linked to greater subsequent Aβ burden in community-dwelling adults, particularly APOE4 carriers.
• Rest-activity fragmentation may represent a modifiable risk factor for Alzheimer disease.
• Further research is warranted to explore interventions targeting activity rhythm regularity for AD prevention.