Grey matter hypometabolism and atrophy in Parkinson's disease with cognitive impairment: a two-step process

Abstract

The pathophysiological process underlying cognitive decline in Parkinson's disease is not well understood. Cerebral atrophy and hypometabolism have been described in patients with Parkinson's disease and dementia or mild cognitive impairment with respect to control subjects. However, the exact relationships between atrophy and hypometabolism are still unclear. To determine the extension and topographical distribution of hypometabolism and atrophy in the different cognitive states of Parkinson's disease, we examined 46 patients with Parkinson's disease (19 female, 27 male; 71.7 ± 5.9 years old; 14.6 ± 4.2 years of disease evolution; modified Hoehn and Yahr mean stage 3.1 ± 0.7). Cognitive status was diagnosed as normal in 14 patients, as mild cognitive impairment in 17 and as dementia in 15 patients. Nineteen normal subjects (eight female, 11 male; 68.1 ± 3.2 years old) were included as controls. (18)F-fluorodeoxyglucose positron emission tomography and magnetic resonance imaging scans were obtained, co-registered, corrected for partial volume effect and spatially normalized to the Montreal Neurological Institute space in each subject. Smoothing was applied to the positron emission tomography and magnetic resonance imaging scans to equalize their effective smoothness and resolution (10 mm and 12 mm full-width at half-maximum and Gaussian kernel, respectively). Z-score maps for atrophy and for hypometabolism were obtained by comparing individual images to the data set of control subjects. For each group of patients, a paired Student's t-test was performed to statistically compare the two Z-map modalities (P < 0.05 false discovery rate corrected) using the direct voxel-based comparison technique. In patients with mild cognitive impairment, hypometabolism exceeded atrophy in the angular gyrus, occipital, orbital and anterior frontal lobes. In patients with dementia, the hypometabolic areas observed in the group with mild cognitive impairment were replaced by areas of atrophy, which were surrounded by extensive zones of hypometabolism. Areas where atrophy was more extended than hypometabolism were found in the precentral and supplementary motor areas in both patients with mild cognitive impairment and with dementia, and in the hippocampus and temporal lobe in patients with dementia. These findings suggest that there is a gradient of severity in cortical changes associated with the development of cognitive impairment in Parkinson's disease in which hypometabolism and atrophy represent consecutive stages of the same process in most of the cortical regions affected.

Keywords: FDG-PET; MRI; Parkinson’s disease; dementia; mild cognitive impairment.

Figure 1

Schematic representation of the procedures for MRI and PET data handling and transformation steps. GM = grey matter.

Figure 2

Regions with reduced FDG-uptake (A) and grey matter volume (B) in patients with Parkinson’s disease with mild cognitive impairment in comparison with control subjects using the MRI and PET Z-score maps, respectively. Cortical areas where hypometabolism exceeded atrophy (C) and where atrophy exceeded hypometabolism (D) in the comparison between MRI and PET Z-score maps.

Figure 3

Regions with reduced FDG-uptake (A) and grey matter volume (B) in patients with Parkinson’s disease with dementia in comparison with control subjects using MRI and PET Z-score maps, respectively. Cortical areas where hypometabolism exceeded atrophy (C) and where atrophy exceeded hypometabolism (D) in the comparison between MRI and PET Z-score maps.

Figure 4

Representation of the extracted mean regional MRI and PET Z-scores in cerebral regions where atrophy exceeded hypometabolism in patients with Parkinson’s disease with mild cognitive impairment (PD-MCI) and patients with Parkinson’s disease with dementia (PDD). On the y- axis, negative values corresponds to higher FDG uptake (white) in patients than in controls and positive values denote reduced FDG uptake. For grey matter volume (grey), positive values indicate reduced grey matter volume and negative values indicate increased grey matter volume. Error bars represent 95% confidence intervals.

Figure 5

Overlapping areas of hypometabolism and atrophy in patients with Parkinson’s disease with MCI (left, PD-MCI) and dementia (right, PDD).