Abstract
Sleep apnea, affecting an estimated 1 in 4 American adults, has been reported to be associated with both brain structural abnormality and impaired cognitive function. Obstructive sleep apnea is known to be affected by upper airway anatomy. To better understand the contribution of upper airway anatomy to pathways linking sleep apnea with impaired cognitive function, we investigated the association of upper airway anatomy with structural brain abnormalities. Based in the Multi-Ethnic Study of Atherosclerosis, a longitudinal cohort study of community-dwelling adults, a comprehensive sleep study and an MRI of the upper airway and brain were performed on 578 participants. Machine learning models were used to select from 74 upper airway measures those measures most associated with selected regional brain volumes and white matter hyperintensity volume. Linear regression assessed associations between the selected upper airway measures, sleep measures, and brain structure. Maxillary divergence was positively associated with hippocampus volume, and mandible length was negatively associated with total white and gray matter volume. Both coefficients were small (coefficients per standard deviation 0.063 mL, p = 0.04, and − 7.0 mL, p < 0.001 respectively), and not affected by adjustment for sleep study measures. Self-reported snoring >2 times per week was associated with larger hippocampus volume (coefficient 0.164 mL, p = 0.007), and higher percentage of time in the N3 sleep stage was associated with larger total white and gray matter volume (4.8 mL, p = 0.004). Despite associations of two upper airway anatomy measures with brain volume, the evidence did not suggest that these upper airway and brain structure associations were acting primarily through the pathway of sleep disturbance.
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Data availability
The data that support the findings of this study are available from the MESA Coordinating Center, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. MESA data are however available from the MESA Coordinating Center upon reasonable request and approval.
Abbreviations
- AHI:
-
apnea hypopnea index
- CASI :
-
Cognitive Abilities Screening Instrument
- SD:
-
standard deviation
- MRI:
-
magnetic resonance imaging
- MESA:
-
Multi-Ethnic Study of Atherosclerosis
- DS:
-
digit span
- Lasso:
-
Least Absolute Shrinkage and Selection Operator
- BMA:
-
Bayesian Model Averaging
- BMI:
-
body mass index
- OSA:
-
obstructive sleep apnea
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Acknowledgements
The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org.
Funding
This research was supported by contracts 75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160,75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168 and N01-HC-95169 and grant R01 HL127659 from the National Heart, Lung, and Blood Institute, and by grants UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420 from the National Center for Advancing Translational Sciences (NCATS). AEF is supported by NIA K01AG071689.
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RN designed the study, performed data analysis, and drafted the work. SH designed the study, obtained funding, and acquired data. RM obtained funding. NB, LD, MH, RS, AW, and SR acquired data. All authors substantially revised the work and approved the submitted version and agreed to be accountable for the integrity and accuracy of all aspects of the work.
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All methods in this study were carried out in accordance with relevant ethical guidelines and regulations. Written informed consent was obtained from all MESA participants. The study was approved by the Institutional Review Board at each field center and the data coordinating center. Each Institutional Review Board is certified by the U.S. Office of Human Research Protections:
Wake Forest University (IRB number IRB00008492 under Federal-wide Assurance- FWA00001435), Columbia University (IRB number IRB00002973 under Federal-wide Assurance- FWA00002636), Johns Hopkins University (IRB number 00001656 under Federal-wide Assurance- FWA00005752), University of Minnesota (IRB number IRB00000438 under Federal-wide Assurance- FWA00000312), Northwestern University (IRB number IRB00005003 under Federal-wide Assurance- FWA00001549), University of California Los Angeles (IRB number 00000172 under Federal-wide Assurance- FWA00004642), University of Washington (IRB number STUDY00009029 under Federal-wide Assurance- FWA00006878).
Competing interests
SR reports consulting fees from Jazz Pharma, Apnimed Inc, and Eli Lilly. RJS reports research grants from ResMed, Inspire, CryOSA, and royalties from UpToDate and Merck Manual. RJS is a research consultant for Eli Lilly and is on the medical advisory board for eXciteOSA. RN, AF, RM, NB, LD, MH, WL, AW, and SH declare that they have no competing interests.
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Nance, R.M., Fohner, A.E., McClelland, R.L. et al. The Association of Upper Airway Anatomy with Brain Structure: The Multi-Ethnic Study of Atherosclerosis. Brain Imaging and Behavior (2024). https://doi.org/10.1007/s11682-023-00843-w
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DOI: https://doi.org/10.1007/s11682-023-00843-w