title: 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.
authors.affiliation: 1 Department of Neurology, Clinica Universidad de Navarra Medical School, Pamplona, Spain2 Neuroscience Centre, CIMA, Pamplona, Spain3 Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: González-Redondo
authors.affiliation: 2 Neuroscience Centre, CIMA, Pamplona, Spain3 Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.
authors.forename: David
authors.initials: D
authors.lastname: García-García
authors.affiliation: 1 Department of Neurology, Clinica Universidad de Navarra Medical School, Pamplona, Spain2 Neuroscience Centre, CIMA, Pamplona, Spain3 Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Clavero
authors.affiliation: 1 Department of Neurology, Clinica Universidad de Navarra Medical School, Pamplona, Spain2 Neuroscience Centre, CIMA, Pamplona, Spain3 Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Gasca-Salas
authors.affiliation: 4 Department of Radiology, Clinica Universidad de Navarra Medical School, Pamplona, Spain.
authors.forename: Reyes
authors.initials: R
authors.lastname: García-Eulate
authors.affiliation: 4 Department of Radiology, Clinica Universidad de Navarra Medical School, Pamplona, Spain.
authors.forename: José L
authors.initials: JL
authors.lastname: Zubieta
authors.affiliation: 5 Department of Nuclear Medicine, Clinica Universidad de Navarra Medical School, Pamplona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Arbizu
authors.affiliation: 1 Department of Neurology, Clinica Universidad de Navarra Medical School, Pamplona, Spain2 Neuroscience Centre, CIMA, Pamplona, Spain3 Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Obeso
authors.affiliation: 1 Department of Neurology, Clinica Universidad de Navarra Medical School, Pamplona, Spain2 Neuroscience Centre, CIMA, Pamplona, Spain3 Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain maria.rodriguezoroz@biodonostia.org.
authors.forename: María C
authors.initials: MC
authors.lastname: Rodríguez-Oroz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001284:Atrophy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D060825:Cognitive Dysfunction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003430:Cross-Sectional Studies; D003704:Dementia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D059906:Neuroimaging / Q000295:instrumentation / Q000379:methods*; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D012720:Severity of Illness Index
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
keywords: FDG-PET; MRI; Parkinson’s disease; dementia; mild cognitive impairment