Magnetic resonance spectroscopy and neurocognitive dysfunction in obstructive sleep apnea before and after CPAP treatment.
OBJECTIVE
To determine whether cerebral metabolite changes may underlie abnormalities of neurocognitive function and respiratory control in OSA.


METHODS
Observational, before and after CPAP treatment.


METHODS
Two tertiary hospital research institutes.


METHODS
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).


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.
Institute for Breathing and Sleep, Austin Health, Heidelberg, Australia. Fergal.ODonoghue@austin.org.au
Fergal J
FJ
O'Donoghue
R Mark
RM
Wellard
Peter D
PD
Rochford
Andrew
A
Dawson
Maree
M
Barnes
Warren R
WR
Ruehland
Melinda L
ML
Jackson
Mark E
ME
Howard
Robert J
RJ
Pierce
Graeme D
GD
Jackson
D000328:Adult; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D045422:Continuous Positive Airway Pressure; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D059906:Neuroimaging / Q000379:methods; D009483:Neuropsychological Tests; D020181:Sleep Apnea, Obstructive / Q000378:metabolism / Q000628:therapy*