Sleep disorders and disturbances in older adults are common, yet frequently undiagnosed and untreated. The prevalence of most sleep problems increases with advancing age and may be attributable to underlying medical or psychiatric conditions, medication use, or sleep abnormalities such as upper airway obstruction referred to as sleep-disordered breathing (SDB). Compelling epidemiological data implicate SDB, particularly intermittent hypoxia (IH), in increasing rates of cardiovascular disease (CVD), cancers and cognitive impairment, including Alzheimer's disease (AD) and related dementias. Although other studies have examined the association of SDB on CVD risk in men and younger women, most are cross-sectional in nature or largely exclude elderly women who are characteristically at high risk of significant vascular disease. No large clinical study has prospectively examined the role of SDB on cancer incidence and aggressiveness, despite strong evidence from animal studies indicating that hypoxemia promotes tumor growth via multiple mechanisms, and on cognitive trajectory and incident mild cognitive impairment (MCI) and AD in older adults. To date, no prior sufficiently powered study has examined the predictive value of SDB for these poor health outcomes in elderly women. We propose to capitalize on the unique and rich, but time-limited resources of the Women's Health Initiative (WHI) that provide a solid infrastructure and an extensive data repository to address key questions regarding the role of SDB and other measures of disturbed sleep on poor health and cognitive outcomes in a large, well-characterized cohort of elderly women. We will leverage resources provided by the WHI Southeast Regional Center at Wake Forest for the conduct of the study and expertise in CVD, cancer, cognitive assessment and MCI/AD; and by Brigham and Women's Hospital/Harvard and California Pacific Medical Center for expertise in sleep, CVD, and cancer. We will use a validated, low burden strategy for data collection that ensures diverse geographical representation at a fraction of the cost associated with clinic-based assessments, including: 1) wrist-worn devices to provide continuous sleep measurements of oxygen desaturation, heart rate, and activity at baseline; 2) mail and telephone assessments; and 3) data sharing with WHI and its ancillary studies. Sleep studies will be conducted using pulse oximetry and actigraphy in 5000 women who are already being followed for CVD and cancer outcomes through other WHI efforts. Adjudicated cancer and CVD outcomes will be collected for 3 years of follow-up, and cognitive function will be assessed via telephone for 3 years of follow-up using well-established validated protocols developed for the WHI Memory Studies. These data may provide the scientific impetus to support the use of new emerging ubiquitously accessible and affordable devices that could provide cost-effective assessments of hypoxemia as part of routine clinical care in patients at highest risk for the negative effects of SDB on CVD and other critical health outcomes.
The proposed study provides an unprecedented opportunity to test the clinical relevance of a simple, home-based approach for identifying modifiable sleep characteristics with potentially powerful prognostic value regarding incident cardiovascular events and cancers, and cognitive decline and impairment ? including Alzheimer's disease and related dementias. Although compelling epidemiological data link disturbed sleep, particularly sleep-disordered breathing characterized by intermittent hypoxia, to increased rates of these poor health outcomes in men and younger cohorts, no sufficiently powered prospective study has examined these relationships in elderly women. The results of this study have the potential to transform routine clinical care to include a cost-efficient sleep assessment for patients at highest risk for CVD, cancers, and cognitive impairment.
