Sex Differences in White Matter Alterations Accompanying Obstructive Sleep Apnea

Abstract
Females with obstructive sleep apnea (OSA) show different psychological and physiological symptoms from males, which may be associated with sex-related variations in neural injury occurring with the disorder. To determine whether male- or female-specific brain injury is present in OSA, we assessed influences of sex on white matter changes in the condition. Two-group factorial. University medical center. 80 subjects total, with newly diagnosed, untreated OSA groups of 10 female (age mean ± SE: 52.6 ± 2.4 years, AHI 22.5 ± 4.1 events/h) and 20 male (age 48.9 ± 1.7, AHI 25.5 ± 2.9) patients, and 20 female (age 50.3 ± 1.7) and 30 male (age 49.2 ± 1.4) healthy control subjects. None. Brain fiber integrity was assessed with fractional anisotropy (FA), a diffusion tensor imaging-derived measure. Sleep quality, daytime sleepiness, depression, and anxiety were assessed with questionnaires. We identified regions of differing injury in male versus female OSA patients by assessing brain regions with significant interaction effects of OSA and sex on FA. Areas of sex-specific, OSA-related FA reductions appeared in females relative to males, including in the bilateral cingulum bundle adjacent to the mid hippocampus, right stria terminalis near the amygdala, prefrontal and posterior-parietal white matter, corpus callosum, and left superior cerebellar peduncle. Females with OSA showed higher daytime sleepiness, anxiety and depression levels, and reduced sleep quality. Sex differences in white matter structural integrity appeared in OSA patients, with females more affected than males. These female-specific structural changes may contribute to or derive from neuropsychological and physiological symptom differences between sexes.