DISRUPTION OF SLEEP AND CIRCADIAN RHYTHM ORGANIZATION AS RISK FACTORS FOR DIAGNOSIS OF ALZHEIMER’S DISEASE

Abstract

Individuals commonly report disrupted nighttime sleep and daytime sleepiness in the early, preclinical, stages of Alzheimer’s disease (AD), as well as other dementias. Furthermore, there is accumulating evidence of a bidirectional relationship between sleep disturbance and AD-related neuropathology (i.e., amyloid-β plaques and neurofibrillary tangles). Despite this, increasing age remains the strongest predictor of late-onset sporadic AD. It is unclear how early in the course of AD sleep-related disturbance manifests and what role these changes have in the etiology of the disease. Moreover, the interplay between sleep and age-related changes to health status, as measured by a frailty index, has not been previously explored. The present dissertation examined the relationship between sleep disturbance and overall health status, including more traditional risk factors for AD, in predicting risk of negative health outcomes, (i.e., cognitive impairment, dementia, and mortality) in cognitively healthy people. Analyses were based on epidemiological data from two large multi-national cohorts, namely the Survey of Health, Ageing, and Retirement in Europe, and the Honolulu-Asia Aging Study. The combination of sleep-related items (i.e., a ‘sleep disturbance index’) was compared to a measure of overall health status (i.e., a ‘frailty index’). Results demonstrate that problems with sleep maintenance, as indicated by disrupted nighttime sleep continuity and daytime sleepiness, are risk factors for cognitive impairment and AD/dementia, up to an average of ~6 years before reported diagnosis, even when risks associated with overall health status are taken into account. By contrast, sleep disturbance was unexpectedly found to decrease risk of mortality when controlling for overall health status. Taken together, sleep disturbance is an important symptom early in the course of cognitive decline and dementia. Further work is required to understand the complex interaction between sleep as a restorative function, and frailty, as a measure of physiological vulnerability to adverse outcomes. Continued exploration of the connections between sleep disturbance, frailty, and dementia, could ultimately identify novel biomarkers leading to the earlier and more accurate diagnosis of AD, as well as guide interventions that could delay institutionalization and/or provide better quality care for those with dementia.