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Research Article: Distinct sleep-disordered breathing phenotypes in elderly patients with depressive disorder: links to hypoxemia severity and inflammatory burden

Date Published: 2026-05-04

Abstract:
To identify sleep-disordered breathing phenotypes in older adults with depressive disorder and obstructive sleep apnea-hypopnea syndrome (OSAHS) and to evaluate their associations with systemic inflammation. Elderly patients with depressive disorder and OSAHS were consecutively enrolled from January to December 2025. A Gower distance matrix was constructed and phenotypes were derived using partitioning around medoids (PAM; k-medoids), with k selected based on silhouette, elbow criteria, and clinical interpretability. Blood samples were collected the morning after PSG to measure serum high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-1? (IL-1?), and tumor necrosis factor-? (TNF-?). Among 198 participants, k = 2 was selected based on internal validity metrics (silhouette and elbow) and clinical interpretability. Compared with the lower-hypoxia/less-severe OSAHS phenotype (Cluster 1, n = 92), the high-hypoxia/severe OSAHS phenotype (Cluster 2, n = 106) had higher BMI, HAMD-17, and ESS, and more severe AHI/ODI/TS90 with a lower LSaO 2 . The high-hypoxia/severe OSAHS phenotype also showed higher hs-CRP, IL-6, IL-1?, TNF-?, WBC, neutrophils, and NLR. The inflammatory burden score was higher in the high-hypoxia/severe OSAHS phenotype (? = 1.10 SD unadjusted; ? = 1.67 SD adjusted for age, sex, BMI, comorbidity, smoking, drinking, education, and MoCA; ? = 1.45 SD further adjusted for HAMD-17 and ESS; all P < 0.001). In men (n = 135), PAM clustering similarly identified two phenotypes differentiated mainly by AHI/ODI, with selective elevations in IL-1? and neutrophil counts. The high-hypoxia/severe OSAHS phenotype in older adults with depressive disorder is independently associated with a higher systemic inflammatory burden.

Introduction:
Obstructive sleep apnea/hypopnea syndrome (OSAHS) is characterized by recurrent episodes of partial or complete upper-airway obstruction during sleep, leading to intermittent reductions in airflow and gas exchange ( 1 ). These events contribute to oxygen deprivation and impaired carbon dioxide elimination, and are commonly accompanied by snoring, sleep fragmentation, and daytime symptoms such as excessive sleepiness and impaired concentration ( 2 ). The global prevalence of OSAHS has been estimated to range from…

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