The Effects of Obstructive Sleep Apnea Syndrome on the Dentate Gyrus and Learning and Memory in Children

Abstract

Obstructive sleep apnea syndrome (OSAS) is associated with intermittent hypoxia and sleep loss. In children, impairments of cognitive function are important manifestations, but the underlying pathology is unknown. We hypothesized that OSAS would affect the dentate gyrus, a hippocampal subdivision essential to neurogenesis and cognition, and that this impact would further affect cognitive function in children. In children with OSAS (n ϭ 11) and control subjects (n ϭ 12; age and sex matched), we performed diffusion tensor imaging and structural MRI, polysomnography, and neuropsychological assessments. We found that OSAS was associated with decreased mean diffusivity of the left dentate gyrus (p ϭ 0.002; false discovery rate corrected; adjusting for sex, age, and body mass index), showing a large effect size (partial 2 ϭ 0.491), but not with any other structural measures across the brain. Decreased dentate gyrus mean diffusivity correlated with a higher apnea hypopnea index (Spearman's r ϭ Ϫ0.50, p ϭ 0.008) and a greater arousal index (r ϭ Ϫ0.44, p ϭ 0.017). OSAS did not significantly affect neuropsychological measures (p values Ͼ0.5); however, a lower verbal learning score correlated with lower dentate gyrus mean diffusivity (r ϭ 0.54, p ϭ 0.004). Path analysis demonstrated that dentate gyrus mean diffusivity mediates the impact of OSAS on verbal learning capacity. Finally, the diagnostic accuracy of a regression model based on dentate gyrus mean diffusivity reached 85.8% (cross validated). This study demonstrates a likely pathway of effects of OSAS on neurocognitive function in children, as well as potential utility of the dentate gyrus mean diffusivity as an early marker of brain pathology in children with OSAS.

Altered Regional Brain Cortical Thickness in Pediatric Obstructive Sleep Apnea

“…Since OSA can go for years undetected, it is unclear how long the participants in our study had the disorder, or how long they neuropsychological performance may have been affected. For example, within the hippocampus, changes in structure measured by water diffusivity are correlated with neuropsychological function ( 37 ). Whether such subtle structural changes extend to the cortex is unclear, but assessment of water diffusion specifically within the cortex is warranted for future studies.…”

Prevalence of childhood obstructive sleep apnea syndrome and its role in daytime sleepiness

“…From a clinical standpoint, the effect of OSAS on cognitive function in children should not be overlooked. Diffusion tensor images from children with OSAS have revealed low mean diffusivity in the dentate gyrus, the part of the hippocampus essential for neurogenesis and cognition, and lower mean diffusivity was associated with lower verbal learning [ 47 ]. Furthermore, childhood OSAS is reported to be associated with behavioral dysregulation (e.g., aggressiveness, impulsivity, and hyperactivity) [ 24 ], [ 48 ] and cognitive dysfunction (particularly attention, executive function, motor function, learning, and memory) [ 49 ].…”

Effect of continuous positive airway pressure therapy on inflammatory cytokines and atherosclerosis in patients with obstructive sleep apnea syndrome

“…Obstructive sleep apnea syndrome (OSAS), which affects 2-4% of the population worldwide, is a common sleep disorder and potential clinical risk factor. OSAS has been widely considered as a severe problem associated with a range of pathological consequences, including hypoxia (1), hypercapnia (2), imbalance of nerve regulation function (3), activation of the rennin angiotensin aldosterone system, catecholamine and endothelin secretion, endocrine dysfunction and hemodynamic changes (4). Of all the problems reported in patients with OSAS, the most important consequence is the risk of cardiovascular and cerebrovascular disease (5).…”