Neurometabolic Response to Apneic Stimuli Tracks Global Grey Matter Volume Deficits in Patients With Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) has been linked to cortical atrophy and increased risk of neurodegeneration, a process potentially mediated by neurometabolic dysregulation. Recent work using high temporal-resolution metabolic MRI found greater changes in the cerebral metabolic rate of oxygen consumption (CMRO₂) during cued breath-hold stimuli simulating spontaneous apneas in OSA patients than in healthy people. Here, we conducted a secondary analysis on this work to assess whether the observed neurometabolic responses were associated with grey matter volume fraction. We examined previously collected data from OSA patients matched to non-OSA participants by age and sex to evaluate associations between MRI-based measures of neurometabolism and grey matter volume. Grey matter volume fraction (GMVF) was computed by segmenting T1-weighted structural images and regressing out age effects in OSA patients relative to the age-matched non-OSA participants. We then examined the relationship between GMVF, apnea-hypopnea index (AHI), and neurometabolic responses of cerebral blood flow (CBF), venous oxygen saturation (SvO₂), and CMRO₂ in response to breath-hold stimuli. OSA severity, expressed in terms of AHI, was negatively associated with GMVF in both OSA and non-OSA reference subjects after controlling for age. Incorporating the quantitative measures of brain oxygen metabolism showed breath-hold responses in CBF and SvO₂ to be positively associated with GMVF. However, changes in CMRO₂ were not significantly associated with age-normalized GMVF. The findings suggest that noninvasive global measures of brain oxygen metabolism may serve as quantitative markers of neural health. Further research is warranted to explore these measures and neurodegenerative risk in OSA.