Self-Reported Sleep Apnea and Dementia Risk: Findings from the Prevention of Alzheimer's Disease with Vitamin E and Selenium Trial

Objectives: To investigate the association between baseline sleep apnea and risk of incident dementia in the Prevention of Alzheimer's Disease with Vitamin E and Selenium (PREADViSE) study and to explore whether the association depends on apolipoprotein E (APOE) ɛ4 allele status. Design: Secondary analysis based on data collected during PREADViSE. Setting: Participants were assessed at 128 local clinical study sites during the clinical trial phase and later were followed by telephone from a centralized location. Participants: Men enrolled in PREADViSE (without dementia or other active neurological conditions that affect cognition such as major psychiatric disorders, including depression; N = 7,547). Measurements: Participants were interviewed at baseline for sleep apnea. The Memory Impairment Screen (MIS) was administered to each participant annually. Subjects who failed this initial screen were tested with secondary screening tests. Medical history and medication use were determined, and the AD8 dementia screening instrument was used. Results: The effect of self-reported sleep apnea on dementia risk depended on APOE ɛ4 status. When the allele was absent, baseline self-reported sleep apnea was associated with a 66% higher risk of developing dementia (95% confidence interval = 2–170%), whereas self-reported sleep apnea conferred no additional risk for participants with an ɛ4 allele. Conclusion: Sleep apnea may increase risk of dementia in the absence of APOE ɛ4. This may help inform prevention strategies for dementia or AD in older men with sleep apnea. Registration: PREADViSE is registered at ClinicalTrials.gov: NCT00040378.