Sex-Specific Association Identified Between Obstructive Sleep Apnea and Dementia

Tiffany Braley, MD

Findings from a cohort of nearly 19,000 people from the Health and Retirement Study (HRS) revealed that obstructive sleep apnea (OSA), a common midlife sleep disorder, may be a significant risk factor for dementia onset, with disproportionate impact on women. Further research is warranted to examine the role of OSA therapy and potential mediators that lie in the pathways between OSA and dementia.

Led by Tiffany Braley, MD, an associate professor of neurology at the Michigan Neuroscience Institute, the analysis included 18,815 women and men aged 50+ years old, of which 9% of women and 8% of men met criteria for incident dementia. The primary exposure of interest was known or suspected OSA, identified through either a self-reported diagnosis or a positive screen on a modified STOP-Bang questionnaire. This questionnaire used medical history, demographic data, and new sleep-related questions added in the 2016-2020 HRS waves.

Within the patient population, the prevalence of known or suspected OSA was more than twice as high in men as in women (68% vs 31%). In unadjusted analyses, results showed that sex influenced the relationship between known or suspected OSA and dementia cumulative incidence (CI). Stratified analyses revealed that, compared to those without OSA, individuals with known or suspected OSA had higher dementia CI between ages 60-84 for both women and men. Notably, differences in dementia CI by OSA status varied with age and sex: as age increased, the gap in dementia CI widened for women but leveled off for men.

OSA was associated with a higher increase of dementia CI for women vs men at every age level observed. For example, at age 80 years, women with versus without known or suspected OSA had a 4.7% higher cumulative dementia incidence (95% CI, 2.8%-6.7%) whereas men versus without known or suspected OSA had only a 2.5% higher cumulative dementia incidence (95% CI, 0.5%-4.5%). At age 80, the population attributable risk percent (PAR%) of dementia linked to OSA was 10.3% for women and 13.2% for men. The lower PAR% in women reflects the lower prevalence of OSA among women (31%) compared to men (68%).

After adjusting for race/ethnicity, education, and cohabitation status, the effect of known or suspected OSA on age-specific dementia risk decreased but remained significant for both sexes. At age 80, women with OSA had a 3.7% higher dementia risk (95% CI: 1.8%, 5.6%), while men with OSA had a 2.1% higher risk (95% CI: 0.1%, 4.1%) compared to those without OSA.

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The connection between poor sleep status and late-life cognitive issues have been documented before in various settings. A first-of-its-kind study presented at the 2022 SLEEP Annual Meeting showed that 3-night withdrawal of continuous airway pressure (CPAP), a treatment for OSA, has an effect on neurodegenerative and amyloid plasma biomarkers. In the study, those off the CPAP treatment showed significant differences in several measures, including percentage of N3 sleep (off: 6.1% [95% CI, 3.7-8.5]; on: 15.1% [95% CI, 10.6-19.6]; P <.001) and percentage of rapid eye movement (REM; off: 11.8% [95% CI, 8.8-14.7]; on: 20.6% [95% CI, 18.3-22.9]; P <.001) compared with those on.²

A community-based prospective study presented earlier this year also showed that OSA severely inversely correlates with the glymphatic system function and that changes in OSA status over time were associated with cognitive performance changes. In this analysis, patients were categorized based on changes in OSA severity over 4 years, and the authors measured glymphatic system function using DTI along the perivascular space (DTI-ALPS) index.³

At baseline, the non-OSA group of patients showed a higher DTI-ALPS index compared with the remaining groups (both, P <.001) and revealed that the apnea-hypopnea index (AHI) was inversely correlated with DTI-ALPS index (R = -.169; P <.001). At follow-up of 4 years, the change in the DTI-ALPS index (ΔDTI-ALPS) was reported the highest in the improved OSA group, followed by the OSA free, stationary OSA, and progressed OSA groups. Notably, the ΔDTI-ALPS over 4-years inversely correlated with ΔAHI (R = -.171; P <.001 for the entire study population and R = -.218; P <.001 for the population which excluded the OSA-free subgroup). Additional findings showed that ΔDTI-ALPS over 4-years correlated with the changes in the visual reproduction–immediate recall (R = .233), delayed recall (R = .178), and recognition (R = .188) scores (all, P <.001).

REFERENCES
1. Braley T, Lyu X, Dunietz L, et al. Sex-specific dementia risk in known or suspected obstructive sleep apnea: a 10-year longitudinal population-based study. Sleep Advances. 2024;5(1). doi:10.1093/sleepadvances/zpae077
2. Kam K, Jun J, Bubu O, et al. Effect of acutely induced severe OSA AD plasma biomarkers. Presented at: SLEEP Annual Meeting, 2022; Charlotte, NC. Abstract 0275
3. Park HJ, Paik SM, Kim JR, et al. Effect of Obstructive Sleep Apnea on the Longitudinal Change in the Glymphatic System Function. Presented at: 2024 SLEEP Annual Meeting; June 1-5; Houston, Texas. Abstract 1006.