Obstructive sleep apnea syndrome (OSAS) is associated with intermittent hypoxia and sleep loss. In children, impairments of cognitive function are important manifestations, but 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=11) and control subjects (n=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=0.002; FDR corrected; adjusting for sex, age, and BMI) showing a large effect size (partial η2=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=-0.50, P=0.008) and a greater arousal index (r=-0.44, P=0.017). OSAS did not significantly affect neuropsychological measures (P's>0.5); however, a lower verbal learning score correlated with lower dentate gyrus mean diffusivity (r=0.54, P=0.004). Path analysis demonstrated that dentate gyrus mean diffusivity mediates the impact of OSAS on the verbal learning capacity. Finally, a 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.
In this study we investigate the relationships between dentate gyrus structure, hippocampus-dependent cognition, and obstructive sleep apnea syndrome (OSAS). We demonstrate lower mean diffusivity of the dentate gyrus in children with OSAS, which correlates with a lower verbal learning and memory score. This study provides new evidence of disrupted microstructure of the dentate gyrus in children with OSAS that may help explain some of the neurocognitive deficits described in these children.
The authors declare no competing financial interests. This study is funded by National Center for Advancing Translational Sciences (NCATS), components of the National Institutes of Health (NIH), through CTSA grant numbers UL1TR001073, L2TR001071 and TL1TR001072; by National Institute of Mental Health (NIMH) through K01-MH109836; and by Brain and Behavior Research Foundation (formally NARSAD) Young Investigator Award.