Brain morphology and functional connectivity alterations in patients with severe obstructive sleep apnea

It has been demonstrated that widespread structural and functional brain alterations influence the development of cognitive impairment in patients with obstructive sleep apnea (OSA). However, the literature has limited evidence regarding the neuropathophysiological mechanisms behind these impairments. This research aimed to investigate brain morphologic and functional connectivity (FC) abnormalities related to neurocognitive function in OSA.Fifty treatment-naïve males, newly diagnosed patients with severe OSA, and 50 well-matched healthy controls (HCs) were enrolled prospectively. All subjects underwent an MRI scan, cognitive psychological and sleep scale assessment. The differences of brain morphological and seed-based FC between the two groups were compared. The correlation analysis and receiver operating characteristic curve were performed for further analysis.Compared with HCs, the right brainstem, left dorsal-lateral superior frontal gyrus (SFGdor), and superior temporal gyrus (STG) exhibited atrophy in the OSA group. In addition, FC between the left SFGdor and the right postcentral gyrus (PoCG) was increased, which was positively correlated with disease duration (r = 0.312, FDR-corrected P = 0.027). The Jacobian values of the brainstem were negatively correlated with MoCA and recall scores (r = -0.449, FDR-corrected P = 0.0025; r = -0.416, FDR-corrected P = 0.005). Furthermore, the Jacobian values of the left SFGdor demonstrated a relatively high diagnostic performance (sensitivity: 86%, specificity: 56%, AUC: 0.740, 95% CI: 0.643-0.836, P < 0.0001).Structural atrophy in brainstem and frontotemporal lobe and altered FC may be the neurobiological hallmark of brain impairment in OSA. Notably, brainstem atrophy has been associated with cognitive impairment, which may provide new insights into understanding the neuropathophysiological mechanisms of cognitive impairment in OSA patients.