Background: Sleep and circadian rhythm disorders are well recognised in both AD (Alzheimer's Disease) dementia and MCI-AD (Mild Cognitive Impairment due to Alzheimer's Disease). Such abnormalities include insomnia, excessive daytime sleepiness, decreased sleep efficiency, increased sleep fragmentation and sundowning. Enhancing understanding of sleep abnormalities may unveil targets for intervention in sleep, a promising approach given hypotheses that sleep disorders may exacerbate AD pathological progression and represent a contributory factor toward impaired cognitive performance and worse quality of life. This may also permit early diagnosis of AD pathology, widely acknowledged as a pre-requisite for future disease-modifying therapies. This study aims to bridge the divide between in-laboratory polysomnographic studies which allow for rich characterisation of sleep but in an unnatural setting, and naturalistic studies typically approximating sleep through use of non-EEG wearable devices. It is also designed to record sleep patterns over a 2 month duration sufficient to capture both infradian rhythm and compensatory responses following suboptimal sleep. Finally, it harnesses an extensively phenotyped population including with AD blood biomarkers. Its principal aims are to improve characterisation of sleep and biological rhythms in individuals with AD, particularly focusing on micro-architectural measures of sleep, compensatory responses to suboptimal sleep and the relationship between sleep parameters, biological rhythms and cognitive performance.
Methods/design: This observational cohort study has two arms (AD-MCI / mild AD dementia and aged-matched healthy adults). Each participant undergoes a baseline visit for collection of demographic, physiological and neuropsychological information utilising validated questionnaires. The main study period involves 7 nights of home-based multi-channel EEG sleep recording nested within an 8-week study period involving continuous wrist-worn actigraphy, sleep diaries and regular brief cognitive tests. Measurement of sleep parameters will be at home thereby obtaining a real-world, naturalistic dataset. Cognitive testing will be repeated at 6 months to stratify participants by longitudinal disease progression.
Discussion: This study will generate new insights particularly in micro-architectural measures of sleep, circadian patterns and compensatory sleep responses in a population with and without AD neurodegenerative change. It aims to enhance standards of remotely based sleep research through use of a well-phenotyped population and advanced sleep measurement technology.
Keywords: AD; Alzheimer’s disease; Circadian; Dementia; EEG; Infradian; MCI; Mild cognitive impairment; Sleep.
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