Nocturnal hypoxemia mediates age-related sleep fragmentation in amyotrophic lateral sclerosis: a polysomnographic case-control study

OBJECTIVE: To evaluate sleep architecture disruptions in amyotrophic lateral sclerosis (ALS) using polysomnography (PSG) and identify clinical/demographic correlates for targeted interventions. METHODS: Forty definite/probable ALS patients (revised El Escorial criteria) without primary sleep disorders and 40 age/sex/BMI-matched controls underwent full polysomnography (PSG). Sleep parameters (total sleep time [TST], sleep efficiency [SE], wake after sleep onset [WASO], N1-N3, rapid eye movement [REM] sleep), respiratory indices (AHI, minimum peripheral oxygen saturation (min SpO₂), SpO₂ range/coefficient of variation [CV]), and clinical metrics (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised [ALSFRS-R], Hospital Anxiety and Depression Scale [HADS]) were compared. Multivariate regression identified independent sleep predictors, and mediation analysis quantified min SpO₂'s role in age-sleep fragmentation relationships. RESULTS: ALS patients showed significantly reduced TST (371.54 ± 67.62 vs. 495.13 ± 45.69 min, p = 0.004), SE (69.95 ± 13.79 vs. 85.10 ± 7.03%, p = 0.009), N2 sleep (127.33 ± 56.75 vs. 204.28 ± 67.16 min, p = 0.013), N3 sleep (61.70 ± 33.67 vs. 91.90 ± 44.06 min, p = 0.021), and REM sleep (66.09 ± 35.85 vs. 84.66 ± 37.65 min, p = 0.012) alongside elevated WASO (131.70 ± 78.82 vs. 64.26 ± 44.18 min, p = 0.015). Nocturnal oxygenation was impaired (min SpO₂: 89.3 ± 3.1% vs. 93.7 ± 2.4%, p < 0.001; SpO₂ CV: 3.7 ± 1.5% vs. 1.8 ± 0.9%, p < 0.001), though AHI and REM AHI were comparable (AHI: p = 0.087; REM AHI: p = 0.134). Age (β = -0.28, p = 0.02) and min SpO₂ (β = 0.31, p = 0.01) independently predicted TST. Mediation analysis confirmed min SpO₂ partially explains age-related TST reduction (indirect effect: -0.14, 95% CI: -0.28 to - 0.03; accounting for 43.8% of the total effect). CONCLUSION: Our data confirm profound sleep architecture disruption and nocturnal hypoxemia in ALS independent of primary sleep disorders. Critically, we establish min SpO₂ as a partial mediator of age-related sleep fragmentation, suggesting that early management of hypoxemia may improve sleep quality. Larger prospective studies validating these mechanisms and their impact on disease progression are warranted.