PROJECT SUMMARY / ABSTRACT Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that leads to cognitive and functional impairment, and is a leading cause of death and disability in aging populations. As there is no cure for AD, current research is focused on understanding early cognitive and behavioral changes to aid in earlier diagnosis and treatment implementation. Older adults are prone to experiencing cognitive changes and changes in sleep function and circadian rhythms, which regulate timing of physiology and behavior across the 24-hour day. Sleep and circadian rhythm disturbances negatively impact cognitive functioning, and are associated with increased risk of cognitive decline and AD dementia. Subjective cognitive decline (SCD) is one of the earliest observable changes preceding objective mild cognitive impairment (MCI), and often signals the need for a cognitive evaluation. There is a paucity of research examining circadian rhythm disturbances in adults experiencing SCD, and it is not well understood how circadian rhythm disturbances may relate to changes in cognitive functioning in this population. Associations with other factors known to relate to sleep and cognitive functions, such as stress, are also understudied in this group. Examining circadian rhythm timing, their associations with cognitive functions, and the influence of stress on these relations in SCD may reveal predictive factors or treatments of cognitive decline targeted to the circadian timing system. The proposed study will examine circadian rhythm timing and cognitive functioning in adults over 50 who (a) are experiencing SCD, (b) have MCI, and (c) are cognitively intact. Dim light melatonin onset (DLMO) testing, actigraphy, and neuropsychological measures will be used to compare circadian rhythm timing and cognitive functioning across these groups (N=90; 30 in each group). This study aims to examine: (1) differences in circadian rhythm timing between study groups; (2) associations between circadian rhythm timing and cognitive functioning in these three groups; and (3) whether perceived stress moderates these associations. It is hypothesized that adults with SCD and MCI will exhibit advanced circadian phase, increased fragmentation, and increased sleep irregularity compared to age-matched cognitively intact adults; that these circadian disruptions will be associated with worse cognitive performance on objective neuropsychological tests; and these associations will be moderated by stress ratings. Through this fellowship, the applicant will gain valuable experience and hands-on training in sleep and neuropsychological research methods and analyses, enabling her to comprehensively examine sleep-related risks of cognitive decline and AD. Furthermore, she will build a network through training and research engagement at Boston University, Brigham and Women’s Hospital, and Massachusetts General Hospital. Together, these experiences will provide her with a deeper understanding of the relations between cognition and sleep in aging populations, and will prepare her for a career as a clinical investigator of predictors and outcomes of age-related cognitive decline.

PROJECT NARRATIVE Older adults are prone to changes in sleep and cognition as they get older, and it has been proposed that sleep and circadian disturbances increase the risk of cognitive decline and dementia. Understanding subtle alterations in circadian rhythm timing in adults at risk of dementia and how such disturbances relate to cognitive functioning will identify potential predictive or treatment targets in the circadian timing system to mitigate age-related cognitive decline. I will investigate: 1) differences in circadian timing among older adults with intact cognition, older adults with subjective cognitive decline, and older adults with mild cognitive impairment; 2) associations between circadian rhythm timing and cognitive functioning in these groups; and 3) whether stress, a modifiable lifestyle factor associated with sleep disturbances and risk of cognitive impairment, moderates the associations between circadian rhythm timing and cognition.