Magnetic resonance spectroscopy and neurocognitive dysfunction in obstructive sleep apnea before and after CPAP treatment

Abstract

Study objectives: To determine whether cerebral metabolite changes may underlie abnormalities of neurocognitive function and respiratory control in OSA.

Design: Observational, before and after CPAP treatment.

Setting: Two tertiary hospital research institutes.

Participants: 30 untreated severe OSA patients, and 25 age-matched healthy controls, all males free of comorbidities, and all having had detailed structural brain analysis using voxel-based morphometry (VBM).

Measurements and results: Single voxel bilateral hippocampal and brainstem, and multivoxel frontal metabolite concentrations were measured using magnetic resonance spectroscopy (MRS) in a high resolution (3T) scanner. Subjects also completed a battery of neurocognitive tests. Patients had repeat testing after 6 months of CPAP. There were significant differences at baseline in frontal N-acetylaspartate/choline (NAA/Cho) ratios (patients [mean (SD)] 4.56 [0.41], controls 4.92 [0.44], P = 0.001), and in hippocampal choline/creatine (Cho/Cr) ratios (0.38 [0.04] vs 0.41 [0.04], P = 0.006), (both ANCOVA, with age and premorbid IQ as covariates). No longitudinal changes were seen with treatment (n = 27, paired t tests), however the hippocampal differences were no longer significant at 6 months, and frontal NAA/Cr ratios were now also significantly different (patients 1.55 [0.13] vs control 1.65 [0.18] P = 0.01). No significant correlations were found between spectroscopy results and neurocognitive test results, but significant negative correlations were seen between arousal index and frontal NAA/Cho (r = -0.39, corrected P = 0.033) and between % total sleep time at SpO(2) < 90% and hippocampal Cho/Cr (r = -0.40, corrected P = 0.01).

Conclusions: OSA patients have brain metabolite changes detected by MRS, suggestive of decreased frontal lobe neuronal viability and integrity, and decreased hippocampal membrane turnover. These regions have previously been shown to have no gross structural lesions using VBM. Little change was seen with treatment with CPAP for 6 months. No correlation of metabolite concentrations was seen with results on neurocognitive tests, but there were significant negative correlations with OSA severity as measured by severity of nocturnal hypoxemia.

Keywords: Neuroimaging; hypoxia; neuropsychological; sleep disordered breathing.

Figure 1

Magnetic resonance spectrum from the hippocampus of a normal subject. The spectrum is a Fourier transformation of resonance frequencies in the voxel of interest. Peaks correspond to concentrations of known metabolites. Cr, total creatine (creatine plus phosphocreatine); mI, myoinositol; Cho, choline containing compounds; Glx, glutamate plus glutamine; Lac, lactate; NAA, N-acetylaspartate plus N-acetylaspartylglutamate.

Figure 2

Position of acquired voxels, superimposed on T1-weighted images. Top row, coronal (left) and sagittal (right) images showing placement of hippocampal voxels. Middle row, left panel: coronal image showing position of brainstem voxel. Middle row, right panel: sagittal image showing brainstem voxel and frontal CSI voxel array. Bottom panel, axial image showing voxel array analyzed from acquired CSI region, (a further outer rim of voxels were discarded to avoid edge artifact).