APOE ɛ4 and REM Sleep Behavior Disorder as Risk Factors for Sundown Syndrome in Alzheimer's Disease

J Alzheimers Dis. 2019;69(2):521-528. doi: 10.3233/JAD-190032.

Abstract

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 APOEɛ4 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 APOEɛ4 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 APOEɛ4 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, APOEɛ4 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 APOEɛ4 allele, RBD, and more severe dementia are associated with an increased risk of SS in AD.

Keywords: APOE; Alzheimer’s disease; REM sleep behavior disorder; circadian rhythm; sundown syndrome.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / epidemiology
  • Alzheimer Disease / etiology*
  • Apolipoprotein E4 / genetics*
  • Chronobiology Disorders / diagnosis
  • Chronobiology Disorders / epidemiology
  • Chronobiology Disorders / genetics*
  • Circadian Rhythm / genetics*
  • Cross-Sectional Studies
  • Female
  • Humans
  • Male
  • REM Sleep Behavior Disorder / diagnosis
  • REM Sleep Behavior Disorder / epidemiology
  • REM Sleep Behavior Disorder / genetics*
  • Risk Factors

Substances

  • Apolipoprotein E4