Sex-specific hippocampus volume changes in obstructive sleep apnea

Abstract

IntroductionObstructive sleep apnea (OSA) patients show hippocampal-related autonomic and neurological symptoms, including impaired memory and depression, which differ by sex, and are mediated in distinct hippocampal subfields. Determining sites and extent of hippocampal sub-regional injury in OSA could reveal localized structural damage linked with OSA symptoms.MethodsHigh-resolution T1-weighted images were collected from 66 newly-diagnosed, untreated OSA (mean age ± SD: 46.3 ± 8.8 years; mean AHI ± SD: 34.1 ± 21.5 events/h;50 male) and 59 healthy age-matched control (46.8 ± 9.0 years;38 male) participants. We added age-matched controls with T1-weighted scans from two datasets (IXI, OASIS-MRI), for 979 controls total (426 male/46.5 ± 9.9 years). We segmented the hippocampus and analyzed surface structure with “FSL FIRST” software, scaling volumes for brain size, and evaluated group differences with ANCOVA (covariates: total-intracranial-volume, sex; P < .05, corrected).ResultsIn OSA relative to controls, the hippocampus showed small areas larger volume bilaterally in CA1 (surface displacement ≤0.56 mm), subiculum, and uncus, and smaller volume in right posterior CA3/dentate (≥ − 0.23 mm). OSA vs. control males showed higher bilateral volume (≤0.61 mm) throughout CA1 and subiculum, extending to head and tail, with greater right-sided increases; lower bilateral volumes (≥ − 0.45 mm) appeared in mid- and posterior-CA3/dentate. OSA vs control females showed only right-sided effects, with increased CA1 and subiculum/uncus volumes (≤0.67 mm), and decreased posterior CA3/dentate volumes (≥ − 0.52 mm). Unlike males, OSA females showed volume decreases in the right hippocampus head and tail.ConclusionsThe hippocampus shows lateralized and sex-specific, OSA-related regional volume differences, which may contribute to sex-related expression of symptoms in the sleep disorder. Volume increases suggest inflammation and glial activation, whereas volume decreases suggest long-lasting neuronal injury; both processes may contribute to dysfunction in OSA.

Brain Structural Features of Myotonic Dystrophy Type 1 and their Relationship with CTG Repeats

“…The limited histological evidence available from previous studies suggest amygdala and hippocampus are not spared from the disease process, in that they exhibit typical hallmarks of DM1 including neurofibrillary tangles [49,57]. Interestingly, sleep disordered breathing has been linked to both regional increases and decreases in hippocampus volume in non-DM1 subjects, held to represent the acute and chronic effects of hypoxia respectively [58]. Further, emerging evidence suggests a functional link between amygdala and control of respiration, with stimulation of the amygdala seen to induce apnea [59].…”

“…Further, respiratory function was not specifically assessed as part of the present study. Sleep-disordered breathing is common in DM1 [66], and has been linked to various structural brain changes in other patient populations [58,67,68], therefore detailed phenotyping of respiratory function including sleep studies should be considered as part of future neuroimaging work. Finally, the clinical impact of the structural changes identified were not explored as part of the present study.…”

Sera of elderly obstructive sleep apnea patients alter blood–brain barrier integrity in vitro: a pilot study

“…This can lead to an interpretation bias and is explained by the fact that diagnoses in females are often under evaluated 52 and that the prevalence of OSAS is higher in males 53 . Nevertheless, studies have shown a gender influence, such as on hippocampal volume in OSAS 23 or greater cortical lesions in women with OSAS 54 . Consequently, sex ratio is a point that will have to be taken into account later on.…”

“…Indeed, the imaging data showed that brain regions near the hippocampus had a volume that could either be increased or decreased. The explanation for an increased volume would be inflammation and activation of glial cells, while a decrease would suggest cell loss leading to neurodegenerative damage 23 . In addition, other studies described a decrease in OSA patients in entropy measurement that indicates an acute change in cerebral tissue and links it to the rupture of the BBB 24,25 .…”

Sex Differences of the Brain Structural Adaptation to Hypoxic Environment

“…There is evidence that sex influences all levels of brain in the extension of brain damages, mechanisms of damages, behavioral outcomes, and treatment efficacies in the neonatal hypoxic-ischaemic models [13][14][15]. Sex-specific cerebral cortices, moleculars, densities of nerve cells, neuroplasticities, iron contents, and cerebral hemodynamic changes were also found in the hypoxic populations [16][17][18]. Clinical data and animal studies confirmed sex differences in hypoxic-ischaemic outcomes, including emotions [19][20][21], cognitions [22], and attention domains.…”