More extensive white matter disruptions present in untreated obstructive sleep apnea than we thought: A large sample diffusion imaging study

Abstract

Obstructive sleep apnea (OSA) may lead to white mater (WM) disruptions and cognitive deficits. However, no studies have investigated the full extent of the brain WM, and its associations with cognitive deficits in OSA remain unclear. We thus applied diffusion tensor imaging (DTI) tractography with multi‐fiber models and used atlas‐based bundle‐specific approach to investigate the WM abnormalities for various tracts of the cerebral cortex, thalamus, brainstem, and cerebellum in patients with untreated OSA. We enrolled 100 OSA patients and 63 healthy controls. Fractional anisotropy (FA) and mean diffusivity (MD) values mapped on 33 regions of interest including WM tracts of cortex, thalamus, brainstem, and cerebellum were obtained from tractography‐based reconstructions. We compared FA/MD values between groups and correlated FA/MD with clinical data in the OSA group after controlling for age and body mass index. OSA patients showed significantly lower FA values in multiple WM fibers including corpus callosum, inferior fronto‐occipital fasciculus, middle/superior longitudinal fasciculi, thalamic radiations, and uncinate (FDR <0.05). Higher FA values were found in medial lemniscus of patients compared to controls (FDR <0.05). Lower FA values of rostrum of corpus callosum correlated with lower visual memory performance in OSA group ( p < .005). Our quantitative DTI analysis demonstrated that untreated OSA could negatively impact the integrity of pathways more broadly, including brainstem structures such as medial lemniscus, in comparison to previous findings. Fiber tract abnormalities of the rostral corpus callosum were associated with impaired visual memory in untreated OSA may provide insights into the related pathomechanism.

Cerebrovascular pathology mediates associations between hypoxemia during rapid eye movement sleep and medial temporal lobe structure and function in older adults

“…Though there was no significant difference between minimum SpO 2 in REM versus NREM in this sample, differences in physiological environment (ventilatory drive, lung O 2 reserve, metabolic demand) between NREM and REM sleep may confer differential impacts of nocturnal hypoxemia to the brain in a stage-dependent manner. Taken together, these data support the hypothesis that respiratory events in REM sleep may play a larger role in triggering gradual loss of adaptive physiology underlying cerebrovascular architecture to cope with ischemic events over time compared to events in NREM sleep 8 .…”

Positive airway pressure improves amnestic mild cognitive impairment in patients diagnosed with obstructive sleep apnoea hypopnoea syndrome. A review of the evidence

“…There is a proposed bidirectional relationship between OSAHS and AD relating to protein accumulation of Aβ and tau and reduced slow wave sleep (Figure 1a) [5]. It has been established with suggested that a lack of slow wave sleep contributes to the formation of Aβ plaques [6,10,11], the accumulation of Aβ in turn hinders slow wave sleep, generating a vicious cycle of events [64]. The mechanisms behind this two-way relationship remain unclear however, it has been proposed to be influenced by inflammation [5,6,64] as described in section 4.1.…”

“…Reduction in brain clearance promote an increase in accumulated metabolites in the brain (such as amyloid beta and tau proteins) [6,56]. An increase in these proteins in the brain have been proposed to form a bidirectional relationship with sleep and therefore contributing to further slow wave sleep disruption due to inflammation interfering with sleep generating pathways [5,64]. This causes a repetitive cycle of events and hence further reductions in the glymphatic system activity [64].…”

“…An increase in these proteins in the brain have been proposed to form a bidirectional relationship with sleep and therefore contributing to further slow wave sleep disruption due to inflammation interfering with sleep generating pathways [5,64]. This causes a repetitive cycle of events and hence further reductions in the glymphatic system activity [64]. Protein accumulation activates astrocytes and microglia as they clear these metabolites from the interstitial space.…”

“…It has been established with suggested that a lack of slow wave sleep contributes to the formation of Aβ plaques [6,10,11], the accumulation of Aβ in turn hinders slow wave sleep, generating a vicious cycle of events [64]. The mechanisms behind this two-way relationship remain unclear however, it has been proposed to be influenced by inflammation [5,6,64] as described in section 4.1. This proposed relationship further supports the amyloid cascade theory (Section 4.1) [6] which leads to neurodegeneration and AD pathology.…”