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

Obstructive sleep apnea (OSA) is commonly associated with memory impairments. Although MRI studies have found volumetric differences in the hippocampus of people with OSA compared with 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 people with OSA (17 females and 15 males) 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 (r(2) = 0.136, p = 0.038), the CA1 (overall, r(2) = 0.135, p = 0.039; layer 1, r(2) = 0.157, p = 0.025; layer 2, r(2) = 0.255, p = 0.003; and layer 3, r(2) = 0.185, p = 0.014) and in some layers of the EC (layer 1, r(2) = 0.186, p = 0.028; trend in layer 3, r(2) = 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, r(2) = 0.282, p = 0.006; deep white matter, r(2) = 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 people with OSA. Statement of Significance Memory deficits are common in people with obstructive sleep apnea (OSA), and although MRI studies have reported hippocampal shrinkage in OSA, they lacked the resolution to investigate individual cell layers that process specific types of memory. The present study used autopsy brain tissue from people with OSA to investigate the thickness and myelination of cell layers in the hippocampus and associated cortex. As OSA severity increased, so did hippocampal atrophy and demyelination. Since the specific cell layers affected are involved in memory processing, they likely underpin the memory impairments. People with OSA that adhered to continuous positive airway pressure therapy showed less hippocampal atrophy but similar demyelination. This irreversibility of white matter damage implies that some memory deficits might be permanent.