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

Abstract

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.

Keywords: APOE; dementia; self-reported sleep apnea.

Conflict of interest statement

The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper.

© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

Figures

Figure 1

Participant flow diagram for PREADViSE *PREADViSE was an ancillary study to SELECT; enrollment was from May 2002 through November 2009 (N=7,547). PREADViSE participants were invited to participate in centralized follow-up (PREADViSE CFU) following the closure of SELECT due to a futility analysis. Some SELECT sites decided not to offer their participants the opportunity to participate in CFU; these participants are listed above as being ineligible. PREADViSE CFU continued to follow participants from August 2010 – August 2015.

Figure 2

Probability of dementia by history of sleep apnea (SDB) at baseline. Solid line indicates sleep apnea, dashed line indicates no sleep apnea. Time axis ends at 10 years for consistency among figures.

Figure 3

Figure 3a & 3b. Probability of dementia at baseline by history of sleep apnea (SDB) status after adjusting other covariates in APOE ε4 non-carriers (a) and carriers (b). These hypothetical participants are white, age 68 at baseline, smoke, have 15 years of education and baseline BMI 28.5 kg/m2, and comorbidities including presence of hypertension and diabetes. Solid line indicates sleep apnea, dashed line indicates no sleep apnea. Time axis ends at 10 years for consistency among figures.

Figure 3

Figure 3a & 3b. Probability of dementia at baseline by history of sleep apnea (SDB) status after adjusting other covariates in APOE ε4 non-carriers (a) and carriers (b). These hypothetical participants are white, age 68 at baseline, smoke, have 15 years of education and baseline BMI 28.5 kg/m2, and comorbidities including presence of hypertension and diabetes. Solid line indicates sleep apnea, dashed line indicates no sleep apnea. Time axis ends at 10 years for consistency among figures.