Apolipoprotein E ɛ4 (APOE ɛ4) Allele is Associated with Long Sleep Duration Among Elderly with Cognitive Impairment

Article type: Research Article

Authors: Basta, Maria^{a; b} | Zaganas, Ioannis^c | Simos, Panagiotis^{a; d} | Koutentaki, Eirini^a | Dimovasili, Christina^c | Mathioudakis, Lambros^c | Bourbouli, Mara^c | Panagiotakis, Symeon^e | Kapetanaki, Stefania^c | Vgontzas, Alexandros^{a; b; *}

Affiliations: [a] Department of Psychiatry, University Hospital of Heraklion, Crete, Greece | [b] Sleep Research and Treatment Center, Department of Psychiatry, Penn State University, Hershey, PA, USA | [c] Department of Neurology, University Hospital of Heraklion, Crete, Greece | [d] Computational Biomedicine Lab, Institute of Computer Science, Foundation for Research and Technology-Hellas, Heraklion, Greece | [e] Department of Internal Medicine, University Hospital of Heraklion, Greece

Correspondence: [*] Correspondence to: Alexandros Vgontzas, MD, Department of Psychiatry, University Hospital of Heraklion, Voutes–Her-aklion, Crete, 71110, Greece. Tel.: +30 28 1039 2402; Fax: +30 28 1039 2859; E-mail: [email protected].

Abstract: Background:Apolipoprotein E gene (APOE) ɛ4 allele increases the risk for Alzheimer’s disease (AD). Furthermore, among patients with cognitive impairment, longer sleep duration is associated with worse cognitive performance. To date, literature examining the associations between APOE ɛ4 allele and objective sleep duration is limited. Objective:Our aim was to assess the association between APOE ɛ4 and objective sleep duration, among patients with mild cognitive impairment (MCI) and AD. A sub-sample of 89 patients with AD (n = 49) and MCI (n = 40) were recruited from a large, population-based cohort of 3,140 elders (>60 years) residing on Crete, Greece. Methods:All participants underwent medical history/physical examination, extensive neuropsychiatric and neuropsychological evaluation, 3-day 24 h actigraphy and APOE ɛ4 allele genotyping. Comparisons of sleep duration variables between APOE ɛ4 allele carriers and non-carriers were assessed using ANCOVA, controlling for confounders. Results:The sample included 18 APOE ɛ4 carriers and 71 non-carriers, aged 78.6±6.6 and 78.2±6.5 years, respectively. Comparisons between the APOE ɛ4 carriers and non-carriers revealed no significant differences in terms of demographic and clinical variables. In terms of objective sleep duration across the two groups, APOE ɛ4 carriers compared to non-carriers had significantly longer nighttime Total Sleep Time (nTST) (7.7±1.4 versus 7.2±1.3  h, respectively, p = 0.011), as well as 24 h TST (8.5±1.6 versus 7.8±1.5  h, respectively, p = 0.012). Conclusion:Among patients with MCI and AD, APOE ɛ4 carriers have longer objective nighttime and 24 h sleep duration compared to non-carriers. These findings further support that objective long sleep duration is a genetically-driven pre-clinical marker associated with worse prognosis in elderly with cognitive impairment.

Keywords: Actigraphy, Alzheimer’s disease, cognitive disorders, genetic risk factors, mild cognitive impairment, sleep

DOI: 10.3233/JAD-200958

Journal: Journal of Alzheimer's Disease, vol. 79, no. 2, pp. 763-771, 2021