White matter microstructure differences in obstructive sleep apnea severity groups assessed by diffusion tensor metrics and biophysical modeling.

Obstructive sleep apnea (OSA) is a complex condition characterized by repeated episodes of upper airway collapse during sleep, leading to chronic intermittent hypoxia. Diffusion magnetic resonance imaging (dMRI) techniques offer sensitivity to white matter (WM) microstructure changes. 150 individuals from a community-based study underwent one-night nocturnal polysomnography (NPSG), cognitive assessments, and brain structural MRI. Gaussian and non-Gaussian diffusion signal changes in WM tracts were quantified with diffusion tensor metrics as (DTI) and Diffusion Kurtosis Imaging (DKI), respectively. While changes in WM microstructure were assessed in terms of Standard Model metrics. The genu of the corpus callosum (GCC) demonstrated negative correlations between AHI3A and FA (p < 0.01), AD (p < 0.05), f (SMI-based axonal water fraction) (p < 0.05), and p2 (p < 0.05) (SMI-based extra-axonal water), alongside positive correlations with RD (p < 0.05). The right cingulum showed negative associations with FA (p < 0.01), RK (p < 0.01), f (p < 0.01) and [Formula: see text](p < 0.01). Subjects without OSA showed higher values in FA (p = 0.001), AD (p = 0.01), f (p = 0.03), and [Formula: see text] (p = 0.0006) in the GCC and cingulum. The strongest differences between severity groups were observed between AHI3A(0–5/h) and AHI3A(> 30/h), particularly in the GCC FA (p = 0.001), RD (p = 0.008), and RK (p = 0.02), and the cingulum f (p ≤ 0.01). Decreases in AD, RK, and FA, and increased RD with increasing OSA severity suggest demyelination and axonal loss. This contrasts with f, a direct measurement for axonal density, which was lower in the OSA group, demonstrating that OSA affects the WM microstructure. Future studies should include longitudinal evaluations to assess the effects of disease duration, and the clinical significance of changes in dMRI metrics over time.