Differential impact of obstructive sleep apnea on hippocampal structure in late middle‐aged and older women and men

Abstract

AbstractBackgroundRecent studies have suggested that obstructive sleep apnea (OSA) could be a modifiable risk factor for dementia. Consequently, efforts have been made to better understand the role of OSA on brain structure integrity, but results between studies are inconsistent. Discrepancies could be partly due to moderating factors (e.g., sex) or complex physiological mechanisms (e.g., oedema) that blur the association between OSA and brain structure. Here, we investigated the association between OSA severity and hippocampal grey matter volume in women and men. We also performed free‐water fraction analyses to understand how oedema could impact hippocampal volumes.MethodSeventy‐three men (age: 65.47±7.22 years; apnea‐hypopnea index [AHI]: 15.52±16.14 events/h; 31 with mild cognitive impairments [MCI]) and 47 women (age: 71.11 ± 6.65; AHI: 11.56 ± 9.92; 22 with MCI) underwent an overnight polysomnography, a neuropsychological evaluation and a magnetic resonance imaging session. Using the hippocampal subfield module in Freesurfer 7.1, total bilateral hippocampal volumes were extracted and normalised to the total intracranial volume. Diffusion data was preprocessed using TractoFlow‐ABS, and Freewater‐Flow and the Sherbrooke Connectivity Imaging Lab scripts were used to extract bilateral hippocampal free‐water fraction. Controlling for age and cognitive status, sex‐stratified linear regressions were performed between (i) the bilateral hippocampal volume or (ii) Free‐water‐corrected bilateral hippocampal volume and log‐transformed AHI.ResultIn women, we observed a positive association between the AHI and bilateral hippocampal volumes (r=0.414; p=0.005), where more severe OSA was associated with higher volumes. This association was not observed in men (p=0.427). When using the free‐water corrected volumes, this association was no longer significant in women (p=0.481), suggesting that the increased hippocampal volume could be due to OSA‐related cytotoxic (intracellular) oedema.ConclusionIn this cohort, while men’s hippocampal volume was unaffected by OSA, women with OSA presented hippocampal hypertrophy likely due to intracellular oedema. Cytotoxic oedema is a known precursor to vasogenic (extracellular) oedema and cell death, suggesting that women might be more vulnerable to the cerebral consequences of OSA than men. Since women have a higher lifetime risk of developing Alzheimer's disease, future studies on OSA should pay a particular attention to women.