Disturbed sleep is commonly observed in patients with poor cognition. Based on existing cross sectional studies, it is unclear whether impaired cognitive function leads to sleep disturbance, or vice versa. Furthermore, most studies have relied on subjective assessment of sleep, which is particularly inaccurate in elderly subjects. We and others have also found that poor sleep quality is associated with increased risk of mortality. However, existing studies are unable to test whether this association is due to poor sleep efficiency independent of intermittent hypoxia. The underlying mechanisms remain unclear. During an eighth examination in the multi-center Study of Osteoporotic Fractures (SOF), we used wrist actigraphy to objectively measure sleep in >3000 older women (mean age 84). SOF, a multi-center observational study supported by NIAMS/NIA, was designed to determine risk factors for osteoporotic fractures in >10,000 older women. Since baseline (1986-88), clinic visits were repeated about every 2 years. All participants are contacted tri-annually to assess incident falls, fractures and deaths. We propose to repeat actigraphy, and perform overnight oximetry and an extended battery of cognitive function tests in 700 older women at two clinic sites during Exam 9. These additional measures in this unique, well-characterized cohort of older women will enable us to address the following specific aims: 1) to explore the longitudinal associations between sleep and cognitive function;2) to determine the independent relationships of actigraphic sleep quality and intermittent hypoxia (using oximetry) with specific domains of cognitive function;3) to test the independent associations of actigraphic sleep quality and intermittent hypoxia on risk of subsequent mortality;4) To determine whether biochemical markers of inflammation (serum IL-6 and CRP), measures of glycemic control (fructosamine), or oxidative burden (myeloperoxidase) mediate the relationships between sleep, cognition and death.
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