Phenotyping of Obstructive Sleep Apnea Syndrome and Association with Cognitive Impairment, a Real-Life Study

Introduction: Obstructive sleep apnea (OSA) is highly prevalent, affecting up to 50% of individuals over 65 years. Elderly patients often present with atypical, fewer and less severe symptoms, suggesting age-specific phenotypes. However, comprehensive clinical phenotyping that incorporates cognitive outcomes remains limited. This study aimed to characterize OSA phenotypes through cluster analysis and evaluate their association with cognitive impairment, independently of age. Materials and Methods: Between 2020 and 2024, 409 adults with moderate-to-severe OSA were enrolled and stratified into three age groups (<65, 65-74, ≥75 years). All underwent home sleep apnea testing (HSAT), comprehensive symptom assessment, Epworth Sleepiness Scale (ESS), and Montreal Cognitive Assessment (MoCA, pathological ≤ 25 pts). Hierarchical cluster analysis (Ward's method) used AHI, T90, BMI, and ESS. Logistic regression identified independent predictors of cognitive impairment. Results: Older groups showed lower BMI, higher comorbidity burden, fewer symptoms, and greater cognitive impairment prevalence (4.5% vs. 9.7% vs. 45.9%; p < 0.001), despite comparable polysomnographic severity across age groups. Cluster analysis identified three phenotypes: Cluster 1 (classical OSA: high AHI, BMI, T90, ESS); Cluster 2 (geriatric phenotype: low AHI, BMI, T90, ESS, highest cognitive impairment rate: 27.7%); Cluster 3 (hypersymptomatic: low AHI and T90, high sleepiness and asthenia, prevalent depression). On multivariate regression, age (OR 1.155; p < 0.001), male sex (OR 2.223; p = 0.034), and Cluster 2 (OR 3.131; p < 0.001) were independent predictors of cognitive impairment. Conclusions: Three clinically distinct OSA phenotypes were identified regardless of age and severity. The geriatric phenotype was associated with three-fold increased risk of cognitive impairment, supporting routine cognitive screening and age-adapted diagnostic strategies in elderly OSA patients.