Aberrant cerebral iron deposition mediates cognitive dysfunction in obstructive sleep Apnea: evidence from a...

Excessive cerebral iron deposition has been implicated in cognitive dysfunction across several neurological disorders. We evaluated severity-dependent patterns of cerebral iron accumulation in obstructive sleep apnea (OSA) using quantitative susceptibility mapping (QSM) and assessed their potential role in mediating cognitive impairment.

The cohort comprised 139 OSA patients, stratified by severity (68 mild-moderate [OSA-M: apnea-hypopnea index (AHI) 5-30 events/hour] and 71 severe [OSA-S: AHI > 30 events/hour]), and 48 healthy controls. All underwent polysomnography, Montreal Cognitive Assessment and 3 T MRI with multi-echo gradient echo sequences for QSM analysis. Whole-brain voxel-wise comparisons characterized iron deposition patterns. Correlation analysis and mediation models evaluated associations between OSA severity, regional iron content, and cognition.

With increasing OSA severity, iron content increased in the bilateral precentral gyri, bilateral medial superior frontal gyri, right putamen and middle cingulate gyrus. Notably, higher QSM values in the left precentral gyrus and right putamen were negatively correlated with cognitive impairment, particularly visuospatial function (p < .05). Mediation analysis demonstrated iron deposition in the right putamen partially mediated associations between AHI, N3 sleep stage proportion, percentage of total sleep time with oxygen saturation < 90%, and cognitive function, particularly visuospatial and executive abilities.

Cerebral iron overload may contribute to cognitive dysfunction across OSA severity levels. The partial mediating effect of putaminal iron supports chronic intermittent hypoxia-induced iron dysregulation as a potential neuropathological mechanism. These findings, predominantly from a male cohort, identify cerebral iron deposition as a potential therapeutic target for mitigating cognitive decline in OSA.