Brain structural changes in obstructive sleep apnea

Abstract

Study objectives: Determine whether obstructive sleep apnea (OSA) subjects show indications of axonal injury.

Design: We assessed fiber integrity in OSA and control subjects with diffusion tensor imaging (DTI). We acquired four whole-brain DTI series from each subject. The four series were realigned, and the diffusion tensor calculated at each voxel. Fractional anisotropy (FA), a measure of fiber integrity, was derived from the diffusion tensor, resulting in a whole brain FA "map." The FA maps were spatially normalized, smoothed, and compared using voxel-based statistics to determine differences between OSA and control groups, with age as a covariate (P < 0.05, corrected for multiple comparisons).

Setting: University medical center.

Subjects: We studied 41 patients with untreated OSA (mean age +/- SD: 46.3 +/- 8.9 years; female/male: 7/34) with apnea-hypopnea index 15 to 101 (mean +/- SD: 35.7 +/- 18.1 events/hour), and 69 control subjects (mean age +/- SD: 47.5 +/- 8.79 years; female/male: 25/44).

Measurements and results: Multiple regions of lower FA appeared within white matter in the OSA group, and included fibers of the anterior corpus callosum, anterior and posterior cingulate cortex and cingulum bundle, right column of the fornix, portions of the frontal, ventral prefrontal, parietal and insular cortices, bilateral internal capsule, left cerebral peduncle, middle cerebellar peduncle and corticospinal tract, and deep cerebellar nuclei.

Conclusions: White matter is extensively affected in OSA patients; the alterations include axons linking major structures within the limbic system, pons, frontal, temporal and parietal cortices, and projections to and from the cerebellum.

Figure 1

Lower FA in 41 OSA vs 69 control subjects. Top: regions overlaid on single subject's anatomical background in sagittal (left) and axial (right) views, color coded according to significance (key at right), with close-up of caudal pons below. Bottom: same regions outlined on background indicating fiber tract direction (average of 110 subjects; directions indicated by lower color key). Locations are in MNI space (relative to anterior commissure). CPons: caudal pons; MCP: middle cerebellar peduncle; CST: corticospinal tract.

Figure 2

Lower FA in 41 OSA vs 69 control subjects in (A) cerebellar deep nuclei, (B) ventral thalamus extending to the hippocampus and temporal cortex, and (C) column of fornix. See Figure 1 for key.

Figure 3

Lower FA in 41 OSA vs 69 control subjects in cerebral peduncle. CP: cerebral peduncle. See Figure 1 for key.

Figure 4

Lower FA in 41 OSA vs 69 control subjects in anterior cingulate area. ACC: anterior cingulate cortex; CB: superior-anterior cingulum bundle; CC: corpus callosum. See Figure 1 for key.

Figure 5

Lower FA in 41 OSA vs 69 control subjects in (A) posterior cingulate areas, (B) left temporal lobe, and (C) deep white matter and areas adjacent to the insula. AI: anterior insula; IFOF: inferior fronto-occipital fasciculus; ILF: inferior longitudinal fasciculus; MI: mid-insula; PC: posterior cingulate cortex/cingulum bundle; PCG: posterior cingulate gyrus; SLF: superior longitudinal fasciculus. See Figure 1 for key.

Figure 6

Lower FA in 41 OSA vs 69 control subjects in prefrontal regions and pre- and postcentral gyri. LFC: later frontal cortex; PFC: prefrontal cortex; PostGyrus: postcentral gyrus; PreGyrus: precentral gyrus; VMFC: ventral medial frontal cortex. See Figure 1 for key.