Neuropathological investigation of cell layer thickness and myelination in the hippocampus of people with obstructive sleep apnea

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Abstract
Obstructive sleep apnea (OSA) is commonly associated with memory impairments. Although MRI studies have found volumetric differences in the hippocampus of OSA patients compared to controls, MRI lacks the spatial resolution to detect changes in the specific regions of the hippocampus that process different types of memory. The present study performed histopathological investigations on autopsy brain tissue from 32 OSA patients (17 female, 15 male) to examine whether the thickness and myelination of the hippocampus and entorhinal cortex (EC) vary as a function of OSA severity. Increasing OSA severity was found to be related to cortical thinning in the molecular layer of the dentate gyrus (r2=0.136, p=0.038), the CA1 (overall, r2=0.135, p=0.039; layer 1, r2=0.157, p=0.025; layer 2, r2=0.255, p=0.003; and layer 3, r2=0.185, p=0.014) and in some layers of the EC (layer 1, r2=0.186, p=0.028; trend in layer 3, r2=0.124, p=0.078). OSA severity was also related to decreased myelin in the deep layers but not the superficial layers of the EC (layer 6, r2=0.282, p=0.006; deep white matter, r2=0.390, p=0.001). Patients known to have used continuous positive airway pressure (CPAP) treatment showed no significant reductions in cortical thickness when compared with controls, suggesting that CPAP had a protective effect. However, CPAP did not protect against myelin loss. The regions of decreased cortical thickness and demyelination are locations of synaptic connections in both the polysynaptic (episodic and spatial) and direct (semantic) memory pathways, and may underpin the impairments observed in episodic, semantic and spatial memory in OSA patients.

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