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Lazar, A. S., Michalak, A., Shabana, Z., Mann, A., Vite, T. G., Conway, T., Grove, V., Tsigarides, J. 
ORCID: https://orcid.org/0000-0001-9893-8002, Gill, N., Tang, J. ORCID: https://orcid.org/0000-0001-6305-6333, Mioshi, E., Wagner, A. ORCID: https://orcid.org/0000-0002-9101-3477, Renoult, L. ORCID: https://orcid.org/0000-0001-7861-0552, Lazar, Z. I., Clark, I., Minihane, A. -M. ORCID: https://orcid.org/0000-0001-9042-4226 and Hornberger, M. ORCID: https://orcid.org/0000-0002-2214-3788
(2022)
Early sleep and circadian markers of alzheimer's disease:the impact of apoe- epsilon 4 on sleep-wake regulation, brain activity and cognition in humans.
Journal of Sleep Research, 31 (S1).
ISSN 0962-1105
Abstract
Introduction: Sleep deficits have been linked to dementia including Alzheimer's disease (AD). TheAPOE-ε4 allele, the genetic risk factor of AD, has been shown to modulate some of these associations albeit with a considerable discrepancy between studies. Objectives: We set out to investigate the effects of theAPOE-ε4status on sleep-wake regulation using observational and experimental study designs in healthy elderly adults. Methods: In total 161 participants (117 female) between 42 and 90 years old have taken part in extensive screening sessions (51 APOE-ε4+, 110 APOE-ε4-) of which 58 (28APOE-ε4+, 30APOE-ε4-) participated in a 14-days-long actigraphy session. Thirty-five individuals (18APOE-ε4+, 17APOE-ε4-) underwent a 2.5-days-long laboratory session in dim light conditions (<10lx). After a baseline night, participants were randomly assigned to either a 40-h sleep deprivation (SD) or a multi-nap(MN) experimental condition followed by a recovery night. Nine 80-min-long naps were scheduled every 4 h in the MN condition. Vigilance, cognition, EEG activity, and postural control (i.e., measured by posturography) were measured on a 4-hourly basis in both experimental conditions. Results: There were no significant genotype differences in either self-reported or polysomnography measured sleep. There was a significant decrease in the actigraphy-measured circadian rest-activity relative amplitude (RA) in the APOE-ɛ4+ subgroup. The genotype did not significantly modulate the effect of sleep loss and circadian phase on cognition. Interestingly the negative effect of sleep loss on balance control was modulated by both sex and APOE status. Men and APOE-ε4 carriers were more affected after sleep loss when both visual and haptic sensorial feedback was provided. Lower self-reported sleep quality was the strongest predictor of worse mental health, independent of age, sex, APOE-ε4 carriership, and other confounding factors. However, this association was stronger in men and APOE-ε4 carriers compared to non-carriers. The known association between increased eveningness and lower subjective sleep quality was present in non-carriers only. Conclusion: APOE is not linked to individual vulnerability to sleep loss but modulates the amplitude of the circadian rest-activity rhythmicity, the effect of sleep deprivation on postural control, and the associations between sleep, brain activity, and mental well-being and cognition in healthy older adults. Disclosure: No
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