Cognitive progression among older adults with subjective cognitive decline and mild cognitive impairment: the roles of sleep and physical frailty - PROJECT SUMMARY Individuals with Subjective Cognitive Decline (SCD) and mild cognitive impairment (MCI) are significantly more likely to have increased AD biomarkers (e.g. amyloid β) and higher risks of developing Alzheimer’s Disease and Related Dementias (ADRD). Sleep disturbances have been associated with increased risks preclinical AD, ADRD, and all-cause dementia. However, most of these studies focus on sleep’s association with the incidence of SCD, MCI, or dementia individually, rather than the progression of cognitive impairment from SCD to MCI to dementia. The latter is of key clinical importance when attempting to halt or treat AD progression. In addition to sleep, recent studies have shown that physical frailty is also closely interrelated with cognitive impairment, with evidence that they predict one another, share common risk factors, and have similar potential mechanisms. The co-existence of both physical frailty and cognitive impairment (MCI/SCD), also known as cognitive frailty, is supposed to be a predictor of severe health consequences with the synergic negative effects of both. However, this synergic effect on future cognitive decline and progression to dementia is still underexamined in the literature. Moreover, given the interrelationship between physical frailty and cognitive impairment, it is possible that physical frailty moderates the associations between sleep disturbances and progression from SCD/MCI to dementia. Therefore, the overall goal of this project is to investigate the roles of sleep disturbances and physical frailty in SCD/MCI’s cognitive progression and explore whether physical frailty is a moderator of sleep’s association with the cognitive progression. In the F99 phase, the PI will use six waves of longitudinal Health and Retirement Study data from the 2010 to 2020 to examine the associations of baseline self-reported insomnia symptoms and physical frailty with 10-year cognitive trajectories and subsequent incidence of MCI/dementia in SCD. In the K00 phase, the PI will shift the population to MCI, a more advanced AD stage, with a focus on actigraphy-measured sleep and neuroimaging cognition measures. The PI will use the UK Biobank data to examine the associations of sleep (both actigraphy-derived and self- reported) and physical frailty with brain structure (magnetic resonance imaging data), subsequent cognitive function, and incident ADRD among older adults with MCI. In both phases, physical frailty will be examined as a moderator in the associations between sleep and cognitive outcomes. This research will help to pinpoint at- risk populations for ADRD, advance understanding of the roles of sleep and physical frailty in ADRD progression in SCD and MCI, and suggest strategies for delaying AD/dementia progression through the lens of sleep and physical frailty. Further, the training objectives nested in the F99 and K00 phases of this award will allow the PI to gain necessary knowledges and skills to develop into an independent investigator in aging research, with a focus on the sleep and cognitive health in older adults.
