Sleep apnea physiological burdens and markers of white matter injury: the Multi-Ethnic Study of Atherosclerosis.

Abstract

Study objectives: Obstructive sleep apnea is associated with cognitive impairment; however, the underlying mechanisms remain incompletely understood. Obstructive sleep apnea is characterized by periods of interrupted ventilation (ventilatory burden), leading to hypoxemia (hypoxic burden) and/or arousal (arousal burden) from sleep. Although hypoxemia is considered a key mechanism underlying white matter injury, its measurement has been limited. In our primary analysis, we assessed the association of hypoxic burden, a quantitative measure of hypoxemia, with white matter hyperintensity volume, a marker of small vessel disease, and compared it with that of ventilatory burden and arousal burden (quantitative measures of ventilatory deficit and arousals).

Methods: Data from participants in the Multi-Ethnic Study of Atherosclerosis with full polysomnograms and brain magnetic resonance imaging were analyzed. Hypoxic burden was defined as the total area under the oxygen desaturation curve per hour of sleep, ventilatory burden was defined as the event-specific area under the ventilation signal, and arousal burden was defined as the normalized cumulative duration of all arousals. The primary outcome was white matter hyperintensity volume, with other magnetic resonance imaging measures considered secondary outcomes.

Results: The analysis included polysomnograms from 587 participants (age: 65.5 ± 8.2 years). In the fully adjusted model, each 1 standard deviation increase in hypoxic burden was associated with a 0.09 standard deviation increase in white matter hyperintensity volume (P = .023), after adjusting for demographics, study site, and comorbidities. In contrast, ventilatory burden, arousal burden, and conventional obstructive sleep apnea measures were not associated with outcomes.

Conclusions: Hypoxic burden was associated with white matter hyperintensity volume in a racially/ethnically diverse cohort of older individuals with a high prevalence of obstructive sleep apnea .

Citation: Hajipour M, Hu W-H, Esmaeili N, et al. Sleep apnea physiological burdens and markers of white matter injury: the Multi-Ethnic Study of Atherosclerosis. J Clin Sleep Med. 2025;21(3):457-466.