The Association of Upper Airway Anatomy with Cognitive Test Performance and Brain Structure: The Multi-Ethnic Study of Atherosclerosis

Sleep apnea, affecting an estimated 1 in 4 American adults, has been reported to be associated with both impaired cognitive function and brain structural abnormality. It is important to explore upper airway anatomy as a risk factor for brain structural abnormality and poor cognitive function both overall and above and beyond its effect on sleep. Nearly 600 participants in the Multi-Ethnic Study of Atherosclerosis underwent upper airway and brain magnetic resonance imaging (MRI), polysomnography to assess sleep measures including the apnea-hypopnea index (AHI) and completed the Cognitive Abilities Screening Instrument (CASI). We used two model selection techniques to select from among over 60 upper airway measures those that are most strongly associated with the CASI, selected regional brain volumes and white matter hyperintensity volume. Linear regression assessed associations between selected upper airway measures, sleep measures, and brain structure or CASI score. Greater soft palate volume, maxillary divergence (reflecting the width of the maxilla), and upper facial height were significantly positively associated with higher CASI score, indicating better cognition. The coefficients were small, with a 1 standard deviation (SD) increase in these variables being associated with a 0.83, 0.75, and 0.70 point higher CASI score, respectively. Additional adjustment for AHI very slightly attenuated these associations. Larger soft palate volume was significantly associated with higher AHI. Higher AHI was marginally associated with higher CASI score. Regarding the brain MRI findings, maxillary divergence was positively associated with hippocampus volume, and mandible length was negatively associated with total white and grey matter volume. Both coefficients were small (coefficient per standard deviation 0.063mL and -7.0mL respectively), and not affected by adjustment for sleep study measures. Self-reported snoring >2 times per week was associated with larger hippocampus volume, and higher percentage of time in the N3 sleep stage (deep sleep) was associated with larger total white and grey matter volume. Not everything was in the hypothesized direction, but maxillary divergence was associated with both outcomes in the hypothesized direction. The magnitudes of the associations were very small and may not be clinically significant. Sleep apnea did not appear to be the mechanism through which these upper airway and cognition or upper airway and brain structure associations were acting. Further research on the selected upper airway measures is recommended.