Effects of long-term treatment on brain volume in patients with obstructive sleep apnea syndrome

Abstract

We assessed structural brain damage in obstructive sleep apnea syndrome (OSA) patients (21 males) and the effects of long-term continuous positive airway pressure (CPAP) treatment (18.2 ± 12.4 months; 8-44 months) on brain structures and investigated the relationship between severity of OSA and effects of treatment. Using deformation-based morphometry to measure local volume changes, we identified widespread neocortical and cerebellar atrophy in untreated patients compared to controls (59 males; Cohen's D = 0.6; FDR < 0.05). Analysis of longitudinally scanned magnetic resonance imaging (MRI) scans both before and after treatment showed increased brain volume following treatment (FDR < 0.05). Volume increase was correlated with longer treatment in the cortical areas that largely overlapped with the initial atrophy. The areas overlying the hippocampal dentate gyrus and the cerebellar dentate nucleus displayed a volume increase after treatment. Patients with very severe OSA (AHI > 64) presented with prefrontal atrophy and displayed an additional volume increase in this area following treatment. Higher impairment of working memory in patients prior to treatment correlated with prefrontal volume increase after treatment. The large overlap between the initial brain damage and the extent of recovery after treatment suggests partial recovery of nonpermanent structural damage. Volume increases in the dentate gyrus and the dentate nucleus possibly likely indicate compensatory neurogenesis in response to diminishing oxidative stress. Such changes in other brain structures may explain gliosis, dendritic volume increase, or inflammation. This study provides neuroimaging evidence that revealed the positive effects of long-term CPAP treatment in patients with OSA.

Keywords: anatomical MRI; continuous positive airway pressure; deformation-based morphometry; intermittent hypoxemia; obstructive sleep apnea syndrome.

© 2015 Wiley Periodicals, Inc.

Figures

Figure 1

Comparison of brain volumes between pre‐CPAP OSA patients and controls. Decreases in overall brain volume (A); in local cortical volume (B); in the left thalamus and bilateral cerebelli (C). Significance values are thresholded at FDR < 0.05. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 2

Effects of CPAP treatment on brain structural volume in OSA patients. A significant volume increase after treatment (no changes in thalamic or cerebellar volume) (A); Volume increase in relation to a longer duration of treatment (B). Arrows indicate locations with the most significant volume increase: the bilateral thalamic lateroposterior nuclei and deep left cerebellar structures. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 3

Qualitative assessment of the pattern of cortical volume changes in patients with OSA. Regions of volume recovery after overall treatment (white), after long‐term treatment (red), and their overlap (shaded red) (A). Regions of atrophy in OSA before treatment (blue), regions of volume recovery after treatment (white), and their overlap (shaded blue) (B). [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 4

Various CPAP effects on brain volume in relation to clinical and neuropsychological conditions prior to treatment. (A). Bilateral medial prefrontal cortices display larger volume recovery in patients with severe OSA (AHI ≥ 64) after CPAP treatment compared to those with a less severe type (AHI ≤ 64). (B). More severe impairment in working memory before treatment induced larger volume increases in bilateral prefrontal and left posterior cingulate cortices after treatment. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 5

Aging effect on brain volume in healthy controls. Top: Cortical volume decrease in relation to Aging; Bottom: Plots showing volume change over ages (%/year) in whole cortical areas as well as other areas than the cortex. There were no volume increases found in cortical or subcortical GM (FDR ≥ 0.1). [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]