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

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.

Posterior parietooccipital hypometabolism may differentiate mild cognitive impairment from dementia in Parkinson's disease.

PURPOSE: Patients with Parkinson's disease (PD) may have normal cognition, mild cognitive impairment (MCI) or dementia. We investigated differences in cerebral metabolism associated with these three cognitive states and the relationship between metabolism and cognitive dysfunction. METHODS: FDG PET and a battery of neuropsychological tests were used to study PD patients with dementia (n = 19), MCI (n = 28) and normal cognition (n = 21), and control subjects (n = 20). Regional glucose metabolism in patients and controls was analysed using statistical parametric mapping (SPM8) corrected for age, motor severity and depression. Correlations between the mini-mental state examination score and Z-score values of the different cognitive domains with respect to cerebral FDG uptake were assessed using SPM8. RESULTS: PD patients with MCI (PD-MCI patients) exhibited decreased FDG uptake in the frontal lobe, and to a lesser extent in parietal areas compared with cognitively normal patients. Patients with dementia showed reduced metabolism in the parietal, occipital and temporal areas and a less extensive reduction in the frontal lobe compared with PD-MCI patients, while widespread hypometabolism was seen in comparison with patients with normal cognition. PD-MCI patients exhibited reduced FDG uptake in the parietal and occipital lobes and in localized areas of the frontal and temporal lobes compared with controls, whereas patients with dementia showed a widespread reduction of cortical metabolism. Mini-mental state examination score correlated positively with metabolism in several lobes, executive function with metabolism in the parietooccipitotemporal junction and frontal lobe, memory with temporoparietal metabolism, visuospatial function with occipitoparietal and temporal metabolism, and language with frontal metabolism. CONCLUSION: PD patients with MCI exhibited hypometabolism in several cortical regions compared with controls, and in the frontal and parietal regions compared with cognitively normal patients. Hypometabolism was higher in patients with dementia than in those with MCI, mainly in the posterior cortical areas where it was correlated with visuospatial, memory and executive functions.

Longitudinal assessment of the pattern of cognitive decline in non-demented patients with advanced Parkinson's disease.

BACKGROUND: Dementia and mild cognitive impairment (MCI) are frequent in Parkinson's disease (PD). Deficits in some cognitive tests are considered risk factors for dementia in PD. However, how cognitive deficits progress in aged and long-lasting non-demented PD is not known. OBJECTIVE: To study the rate and pattern of progression of cognitive deficits in aged and long-lasting non-demented PD. METHODS: Forty-nine non-demented patients (23 cognitively normal (PD-CN) and 26 with MCI (PD-MCI)) were studied over 31 months using individual tests and z-scores covering five cognitive domains. All patients were at least 60 year old and have had PD ≥ 10 years. RESULTS: Attention, executive function and memory worsened in 5 PD-CN patients who progressed to MCI (21.7% of the sample) and in 1 patient who became demented (4.3% of the sample). Eleven PD-MCI patients who developed dementia (42.3% of the sample) showed aggravation of visuospatial, executive and attention domains. Multidomain-MCI and poor execution of Stroop-Words, copy of intersecting pentagons and Raven Progressive Matrices tests were associated with conversion to dementia. CONCLUSIONS: This pilot study shows that in long-lasting PD 21.7% of PD-CN patients progress to MCI and 42.3% of PD-MCI progress to dementia over a 31 months observation period. The transition from cognitively normal to MCI is featured by attention, executive and memory dysfunction and the evolution from MCI to dementia is marked by the appearance of visuospatial deficits and worsening of attention and executive function. These data are compatible with the concept that cognitive decline in PD follows a distinct dysfunction pattern with progressive anterior to posterior cortical involvement.

Effect of deep brain stimulation of the subthalamic nucleus on non-motor fluctuations in Parkinson's disease: two-years' follow-up.

BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN-DBS) reduces motor fluctuations in Parkinson's disease (PD) but its effect on non-motor fluctuations (NMF) is not well known. In this study we assess the efficacy of STN-DBS on NMF two years after surgery. METHODS: Autonomic, cognitive, psychiatric and sensory NMF in 20 patients were evaluated using a questionnaire designed to assess the frequency and severity of the NMF preoperatively and after two years of follow-up. The UPDRS scale was used for assessing the motor state. RESULTS: Compared with the preoperative situation, STN-DBS at 2 years of follow-up was associated with a significant reduction in the number and severity of autonomic and psychiatric NMF in the "off" state (without medication), and in the severity of sensory NMF, which were not observed in the "on" state (with medication). A cross-sectional analysis at the two-year time-point of the four possible motor conditions (combining medication and stimulation) showed a reduction in the total number of NMF and in the severity of autonomic and sensory NMF after switching on the stimulation in the "on" state. Improvement of the UPDRS-motor score was correlated with a reduction in the severity but not in the frequency of NMF. A worsening of motor function after suppressing stimulation in the "off" state was not paralleled by a worsening of NMF. CONCLUSION: After two years of follow-up, STN-DBS in the "off" medication was associated with a reduction in the frequency and severity of NMF. These results will need to be confirmed in controlled studies.