Association of Rest Activity Rhythm and Risk of Developing Dementia or Mild Cognitive Impairment in the middle-aged and older population (Preprint)

BACKGROUND The relationship between 24-h rest-activity rhythms (RAR) and risk for dementia or mild cognitive impairment (MCI) remains an area of growing interest. Previous studies, often limited by small sample sizes, short follow-ups, and older participants, has yet to fully explore the link between disrupted RAR and dementia/MCI in middle-aged and older adults. OBJECTIVE We leveraged the UK Biobank data to examine how RAR disturbances correlate with the risk of developing dementia and MCI in middle-aged and older adults. METHODS We analyzed data of 94,145 UK Biobank participants between 43-79 years old. Wrist actigraphy recordings were used to derive nonparametric RAR metrics, including the activity level of the most active 10-hour period (M10) and its midpoint, the activity level of the least active 5-hour period (L5) and its midpoint, relative amplitude of the 24-hour cycle [RA=(M10-L5)/(M10+L5)], interdaily stability (IS), and intradaily variability (IV), as well as the amplitude and acrophase of 24-h rhythms (cosinor analysis). We conducted Cox proportional hazards models to examine the associations between baseline RAR and subsequent incidence of dementia/MCI, adjusting for demographic characteristics, comorbidities, lifestyle factors, shiftwork status, and genetic risk for Alzheimer’s disease. RESULTS During the follow-up of up to 7.5 years, 575 participants developed MCI/dementia. The dementia/MCI risk increased for lower M10 activity (HR=1.29 [1.15-1.45] for 1-SD decrease), higher L5 activity (HR=1.15 [1.09-1.21] for 1-SD increase), lower RA (HR[95%CI]=1.23 [1.17-1.30] for 1-SD decrease), lower amplitude (HR=1.31 [1.16-1.48] for 1-SD decrease), and higher IV (HR=1.13 [1.04-1.23] for 1-SD increase) as well as advanced L5 midpoint (HR=0.91 [0.84-0.98] for 1-SD advance). These associations were similar in people <70 and >70 years old, in non-shift workers, and were independent of genetic and cardiovascular risk factors. No significant associations were observed for M10 midpoint, IS, or acrophase. CONCLUSIONS : Utilizing a large sample of middle-to-older adults, with objective RAR assessment and almost 8-years of follow-up, our findings suggest that suppressed and fragmented daily activity rhythms preceded the onset of dementia/MCI and may serve as risk biomarkers for preclinical dementia in the middle-aged and older adults.