Sleep genes and Circadian rhythm in dementia prevention

Changes in sleep patterns are common among people with dementia, however why short (≤6hrs) or long sleep (≥9hrs) duration is less favorable for dementia, remains unknown. Given that approximately 46% & 44% of variability in sleep duration is explained by genetics, it is pertinent to consider genetic influences when understanding the mechanisms contributing to sleep-related risk for dementia. In addition to sleep, there is growing interest in the relationship between circadian rhythms, the 24-hour cycles of body & dementia. Links between Alzheimer’s’ dementia and the circadian system are suggested by common observations that an early symptom of Alzheimer’s’ dementia is fragmented sleep/wake patterns with increasing night\time activity and daytime naps. Even among individuals who are cognitively intact, altered circadian rhythms of motor activity have been linked to amyloid pathology; the hallmark of Alzheimer’s’ dementia. There is some evidence linking weakening circadian rhythm to dementia, yet it is not clear whether disruption of clock contributes to incidence dementia. In CLOCKED, I will use data from the Swedish Twin Registry with over 20 years of follow-up, the largest twin registry in the world to assess if sleep polygenic risk score influences the risk of incident dementia (overall, Alzheimer’s’, vascular) & examine whether differences in dementia risk are influenced by a genetically predicted sleep or sleep driven mainly by non-genetic factors, i.e., environmental lifestyle factors. Using accelerometry data on around 100,000 participants from the UK Biobank data, I will assess the relation of accelerometer-assessed circadian rhythmicity with incident dementia & quantify dementia risk stratified by sex, ethnicity, socioeconomic status, shift work, lifestyle factors, & metabolic status; and determine whether a risk score consisting of circadian factors (i.e., circadian syndrome) is a more accurate predictor for dementia than existing risk scores.