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

Abstract

Regional cerebral phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) was performed in 10 non- demented Parkinson's disease patients and nine age-matched control subjects. Five of the patients undergoing (31)P-MRS and four additional Parkinson's disease patients had cerebral 2-[(18)F]fluoro-2-deoxy-D-glucose PET ((18)FDG-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. (31)P MR spectra from right and left temporo-parietal cortex, occipital cortex and a central voxel incorporating basal ganglia and brainstem were obtained. (31)P MR peak area ratios of signals from phosphomonoesters (PMEs), inorganic phosphate (P(i)), phosphodiesters (PDEs), alpha-ATP, gamma-ATP and phosphocreatine (PCr) relative to beta-ATP were measured. Relative percentage peak areas of PMEs, P(i), PDEs, PCr, and alpha-, beta- and gamma-ATP signals were also measured with respect to the total (31)P-MRS signal. Significant bilateral increases in the P(i)/beta-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). (18)FDG-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)/beta-ATP ratios and estimated reductions in performance IQ (r = 0.96, P < 0.001). Left temporoparietal P(i)/beta-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 (31)P-MRS and (18)FDG-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. (31)P-MRS and (18)FDG-PET may both provide useful predictors of future cognitive impairment in a subset of Parkinson's disease patients who go on to develop dementia.

Regional Gray Matter Atrophy in Patients with Parkinson Disease and Freezing of Gait

“…Nevertheless, our results are consistent with several imaging studies reporting an association between reduced cerebral glucose uptake in extensive posterior cortical areas and cognitive impairment in patients with PD. [38][39][40] Taken together, our imaging and neuropsychological findings highlight the role of cognitive neural networks in the pathophysiology of FOG in PD. It has been demonstrated that patients with FOG have a pathologic gait pattern, 41 even between FOG episodes.…”

Imaging Approaches to Parkinson Disease

“…This pattern of reduced glucose metabolism is similar to that reported in Alzheimer disease (95), suggesting that Lewy body and Alzheimer pathology are associated with overlapping patterns of cortical neuronal dysfunction. Temporoparietal cortical hypometabolism can also be observed in a minority of nondemented PD patients with established disease, suggesting that subclinical cortical Lewy body involvement may already be present (96). It remains to be determined whether the observed glucose hypometabolism in these subjects is a predictor of late-onset dementia.…”

The basal ganglia and semantic engagement: Potential insights from semantic priming in individuals with subcortical vascular lesions, Parkinson's disease, and cortical lesions

“…Consequently, Parkinson's disease has been used extensively as a model for exploring cognitive functions of the basal ganglia (e.g., Brown & Marsden, 1998;Taylor et al, 1986;Ullman et al, 1997). Any assumption that cognitive deficits in PD reflect striatal dysfunction should be made cautiously, however, given that (1) various frontal regions may be affected by the degeneration of mesolimbic and mesocortical dopaminergic pathways also, which have been implicated in cognitive changes (Javoy-Agid & Agid, 1980;Scatton et al, 1982), and (2) certain cognitive deficits in PD may relate to other cortical dysfunction (Hu et al, 2000), or neurochemical alterations including cholinergic systems with cortical and subcortical projections (e.g., Bedard et al, 1999). In addition, differences may be expected in the language processing of PD and NS lesion groups, given the different effects of dopaminergic deafferentation of the striatum versus structural lesions of striatal tissue on striatal output and function (Crosson, 1992b).…”