Association between Obstructive Sleep Apnea and Brain White Matter Hyperintensities in a Population-Based Cohort in Germany

Helena U. Zacharias, Antoine Weihs, Mohamad Habes, Katharina Wittfeld, Stefan Frenzel, Tanweer Rashid, Beate Stubbe, Anne Obst, András Szentkirályi, Robin Bülow, Klaus Berger, Ingo Fietze, Thomas Penzel, Norbert Hosten, Ralf Ewert, Henry Völzke, Hans J. Grabe

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Importance: Underlying pathomechanisms of brain white matter hyperintensities (WMHs), commonly observed in older individuals and significantly associated with Alzheimer disease and brain aging, have not yet been fully elucidated. One potential contributing factor to WMH burden is chronic obstructive sleep apnea (OSA), a disorder highly prevalent in the general population with readily available treatment options. Objective: To investigate potential associations between OSA and WMH burden. Design, Setting, and Participants: Analyses were conducted in 529 study participants of the Study of Health in Pomerania-Trend baseline (SHIP-Trend-0) study with complete WMH, OSA, and important clinical data available. SHIP-Trend-0 is a general population-based, cross-sectional, observational study to facilitate the investigation of a large spectrum of common risk factors, subclinical disorders, and clinical diseases and their relationships among each other with patient recruitment from Western Pomerania, Germany, starting on September 1, 2008, with data collected until December 31, 2012. Data analysis was performed from February 1, 2019, to January 31, 2021. Exposures: The apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) were assessed during a single-night, laboratory-based polysomnography measurement. Main Outcomes and Measures: The primary outcome was WMH data automatically segmented from 1.5-T magnetic resonance images. Results: Of 529 study participants (mean [SD] age, 52.15 [13.58] years; 282 female [53%]), a total of 209 (40%) or 102 (19%) individuals were diagnosed with OSA according to AHI or ODI criteria (mean [SD] AHI, 7.98 [12.55] events per hour; mean [SD] ODI, 3.75 [8.43] events per hour). Both AHI (β = 0.024; 95% CI, 0.011-0.037; P <.001) and ODI (β = 0.033; 95% CI, 0.014-0.051; P <. 001) were significantly associated with brain WMH volumes. These associations remained even in the presence of additional vascular, metabolic, and lifestyle WMH risk factors. Region-specific WMH analyses found the strongest associations between periventricular frontal WMH volumes and both AHI (β = 0.0275; 95% CI, 0.013-0.042, P <.001) and ODI (β = 0.0381; 95% CI, 0.016-0.060, P <.001) as well as periventricular dorsal WMH volumes and AHI (β = 0.0165; 95% CI, 0.004-0.029, P =.008). Conclusions and Relevance: This study found significant associations between OSA and brain WMHs, indicating a novel, potentially treatable WMH pathomechanism..

Original languageEnglish (US)
JournalJAMA network open
StateAccepted/In press - 2021

ASJC Scopus subject areas

  • General Medicine


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