Cortical dysfunction in non-demented Parkinson's disease patients. A combined ³¹P-MRS and ¹⁸FDG-PET study

Regional cerebral phosphorus-31 magnetic resonance spectroscopy (³¹P-MRS) was performed in 10 non-demented Parkinson's disease patients and nine age-matched control subjects. Five of the patients undergoing ³¹P-MRS and four additional Parkinson's disease patients had cerebral 2-[¹⁸F]fluoro-2-deoxy-D-glucose PET (¹⁸FDG-PET), the results of which were compared with those of eight age-matched control subjects. All Parkinson's disease patients underwent neuropsychological testing including performance and verbal subtests of the Wechsler Adult Intelligence Scale - Revised, Boston Naming Test, Controlled Oral Word Association test (FAS Test) and California Learning Test to exclude clinical dementia. ³¹P MR spectra from right and left temporo-parietal cortex, occipital cortex and a central voxel incorporating basal ganglia and brainstem were obtained. ³¹P MR peak area ratios of signals from phosphomonoesters (PMEs), inorganic phosphate (P(i)), phosphodiesters (PDEs), α-ATP, γ-ATP and phosphocreatine (PCr) relative to β-ATP were measured. Relative percentage peak areas of PMEs, Pi, PDEs, PCr, and α-, β- and γ-ATP signals were also measured with respect to the total ³¹P-MRS signal. Significant bilateral increases in the P(i)/β-ATP ratio were found in temporoparietal cortex (P = 0.002 right and P = 0.014 left cortex) for the non-demented Parkinson's disease patients compared with controls. In the right temporoparietal cortex, there was also a significant increase in the mean relative percentage P(i) (P = 0.001). ¹⁸FDG-PET revealed absolute bilateral reductions in glucose metabolism after partial volume effect correction in posterior parietal and temporal cortical grey matter (P < 0.01 and P < 0.05, respectively) for the Parkinson's disease group, using both volume of interest analysis and statistical parametric mapping. There were significant correlations between right temporoparietal P(i)/β-ATP ratios and estimated reductions in performance IQ (r = 0.96, P < 0.001). Left temporoparietal P(i)/β-ATP ratios correlated with full scale IQ and verbal IQ (r = -0.82, P = 0.006, r = -0.86, P = 0.003, respectively). In summary, temporoparietal cortical hypometabolism was seen in non-demented Parkinson's disease patients with both ³¹P-MRS and ¹⁸FDG-PET, suggesting that both glycolytic and oxidative pathways are impaired. This dysfunction may reflect either the presence of primary cortical pathology or deafferentation of striato-cortical projections. ³¹P-MRS and ¹⁸FDG-PET may both provide useful predictors of future cognitive impairment in a subset of Parkinson's disease patients who go on to develop dementia.