Study Finds Significant Link Between Obstructive Sleep Apnea, White Matter Hyperintensities

Patients with obstuctive sleep apnea were found to be significantly more likely to have brain white matter hyperintensities, lesions known to signal brain aging and potential risk of Alzheimer disease.

Incidence of obstructive sleep apnea (OSA) may contribute to the development of brain white matter hyperintensities (WMHs), a known marker of brain aging that has been associated with neurodegenerative disease pathology. Findings were published today in JAMA Network Open.

Commonly found in MRIs of older adults, individuals with dementia, and patients with stroke history, brain WMHs have been linked with vascular and neurodegenerative risk factors. Although the pathophysiology of WMHs remains unclear, researchers of this new study noted previous research that suggested ischemia or hypoxia and hypoperfusion, main characteristics of OSA, as possible pathogenic mechanisms.

“OSA has been identified as a significant risk factor for cardiovascular, metabolic, and psychiatric disorders,” they added. “So far, however, the association between OSA and white matter disease, both highly prevalent in older individuals, has been investigated by only a few human studies, with contradictory findings.”

Leveraging data from Study of Health in Pomerania–Trend baseline (SHIP-Trend-0), a population-based, cross-sectional, observational study, they sought to analyze the potential 2-way interactions between OSA and metabolic, vascular, and lifestyle WMH risk factors, as well as specific OSA associations in individual brain WMH regions.

Eligible participants from Western Pomerania, Germany, provided complete WMH, OSA, and other important clinical data between September 1, 2008 and December 31, 2012 (N = 529; mean [SD] age, 52.15 [13.58] years; 282 women [53%]).

Assessed metabolic, vascular, and lifestyle WMH risk factors included hypertension, waist circumference, triglyceride, total cholesterol, low- and high-density lipoprotein cholesterol levels, diabetes, lifetime depression, subjective mental health, smoking, daily alcohol consumption, educational level, and physical activity.

In evaluating the primary outcome of WMH data automatically segmented from 1.5-T MRIs, OSA parameters of apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) were investigated and collected during a single-night, laboratory-based polysomnography (PSG) measurement.

Of the study cohort, 209 individuals (40%) received an OSA diagnosis, according to AHI criteria (mean [SD] AHI, 7.98 [12.55] events per hour), and 102 (19%) individuals received an OSA diagnosis according to ODI criteria (mean [SD] ODI, 3.75 [8.43] events per hour). Participants with OSA were older, had higher blood pressure, and higher glycated hemoglobin values than those who did not have OSA.

Notably, WMH volumes were significantly positively associated with 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) in multivariable linear regression models adjusted for sex, age, intracranial volume, and body height. These associations remained significant even in the presence of additional vascular, metabolic, and lifestyle WMH risk factors, noted the study authors.

As for region-specific WMH associations, analyses indicated that the strongest link was found 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), and periventricular dorsal WMH volumes with AHI (β = 0.0165; 95% CI, 0.004-0.029; P = .008).

No significant interactions were observed between the assessed WMH risk factors and AHI, whereas 1 significant interaction was found for ODI, with current smoking, on WMH counts (β = 0.030; 95% CI, 0.0039-0.056; P = .03).

As the search for preventive and therapeutic strategies to reduce WMH burden remains ongoing, the researchers concluded that future studies could investigate the effect of OSA on WMH burden in specific OSA populations and the effect of OSA treatments on WMH burden.


Zacharias HU, Weihs A, Habes M, et al. Association between obstructive sleep apnea and brain white matter hyperintensities in a population-based cohort in Germany. JAMA Netw Open. Published online October 5, 2021. doi:10.1001/jamanetworkopen.2021.28225