Gray Matter Hypertrophy and Thickening with Obstructive Sleep Apnea in Middle-aged and Older Adults

Abstract

Rationale: Obstructive sleep apnea causes intermittent hypoxemia, hemodynamic fluctuations, and sleep fragmentation, all of which could damage cerebral gray matter that can be indirectly assessed by neuroimaging.

Objectives: To investigate whether markers of obstructive sleep apnea severity are associated with gray matter changes among middle-aged and older individuals.

Methods: Seventy-one subjects (ages, 55-76 yr; apnea-hypopnea index, 0.2-96.6 events/h) were evaluated by magnetic resonance imaging. Two techniques were used: (1) voxel-based morphometry, which measures gray matter volume and concentration; and (2) FreeSurfer (an open source software suite) automated segmentation, which estimates the volume of predefined cortical/subcortical regions and cortical thickness. Regression analyses were performed between gray matter characteristics and markers of obstructive sleep apnea severity (hypoxemia, respiratory disturbances, and sleep fragmentation).

Measurements and main results: Subjects had few symptoms, that is, sleepiness, depression, anxiety, and cognitive deficits. Although no association was found with voxel-based morphometry, FreeSurfer revealed increased gray matter with obstructive sleep apnea. Higher levels of hypoxemia correlated with increased volume and thickness of the left lateral prefrontal cortex as well as increased thickness of the right frontal pole, the right lateral parietal lobules, and the left posterior cingulate cortex. Respiratory disturbances positively correlated with right amygdala volume, and more severe sleep fragmentation was associated with increased thickness of the right inferior frontal gyrus.

Conclusions: Gray matter hypertrophy and thickening were associated with hypoxemia, respiratory disturbances, and sleep fragmentation. These structural changes in a group of middle-aged and older individuals may represent adaptive/reactive brain mechanisms attributed to a presymptomatic stage of obstructive sleep apnea.

Keywords: aging; cerebral cortex; hypoxemia; neuroimaging; sleep-disordered breathing.