APOE ε4 and REM Sleep Behavior Disorder as Risk Factors for Sundown Syndrome in Alzheimer's Disease

Background: Sundown syndrome (SS) in patients with Alzheimer's disease (AD) is characterized by aggravation of behavioral problems at sunset. Disturbance of the circadian rhythm, a possible cause of SS, also facilitates amyloidopathy and reduces sleep quality. However, the associations of SS with amyloidopathy and sleep quality remain unclear. Objective: To investigate the prevalence of SS in patients with AD, the association between SS and APOE epsilon 4 carrier, representing an enhanced amyloid pathology, and the relationship between SS and sleep quality in AD. Methods: We included 104 patients with late-onset AD and known APOE genotype. All participants underwent a structured interview via informant-based questionnaires to assess sleep quality and the presence of SS. Binary logistic regression analysis was performed to determine odds ratios (ORs) of APOE epsilon 4 carrier and parameters of sleep quality for SS. Results: The prevalence of SS in AD was 27.8% (n= 29). Patients with SS were significantly more likely to be APOE epsilon 4 carriers and to have rapid eye movement sleep behavior disorder (RBD) and a higher Clinical Dementia Rating (CDR) score compared to those without SS. In the multivariate regression analysis, APOE epsilon 4 carrier (OR 3.158, CI 1.022-9.758), RBD (OR 2.166, CI 1.073-4.371), and higher CDR score (OR 2.453, CI 1.084-5.550) were associated with an increased risk of SS. Conclusion: The prevalence of SS in patients with AD was 27.8%. The presence of the APOE epsilon 4 allele, RBD, and more severe dementia are associated with an increased risk of SS in AD.