title: Cerebral glucose metabolic features of Parkinson disease and incident dementia: longitudinal study.
abstract: Longitudinal studies in nondemented Parkinson disease (PD) subjects offer an opportunity to study the earliest regional cerebral subcortical and cortical metabolic changes underlying incident dementia in this disorder.
  
  
  METHODS
  Twenty-three PD subjects without dementia (Hoehn and Yahr stages I-III; age, 61.8 ± 9.7 y; Mini-Mental State Examination, 28.0 ± 1.4) and 27 controls (age, 59.8 ± 11.5 y) underwent (18)F-FDG PET at study entry. PD subjects underwent yearly clinical assessment to determine conversion to dementia. The mean duration of follow-up was 3.9 ± 1.2 y (range, 2.0-6.8 y). Follow-up (18)F-FDG PET was available in a subset of subjects at 2 or more years. Both volume-of-interest and 3-dimensional stereotactic surface projection (3D-SSP) analyses were performed.
  
  
  RESULTS
  Six subjects became demented (PDD), with a mean time of 3.8 ± 1.7 y (range, 1.9-6.0 y) to development of dementia. Mean duration of disease before onset of dementia was 9.7 ± 4.2 y (range, 3.1-14 y). There were significant metabolic reductions in the occipital (-11.8% vs. controls, F((2,22)) = 7.0, P = 0.002) and posterior cingulate (-12.1% vs. controls, F((2,22)) = 5.2, P = 0.009) cortices in PDD subjects at baseline, before diagnosis of dementia, compared with controls. Metabolism was most diminished in the visual association cortex (Brodmann area [BA] 18; -20.0% vs. control, F((2,22)) = 8.45, P = 0.0007) of PDD subjects. There was mild hypometabolism in the caudate nucleus (-8.4% vs. control, F((2,22)) = 3.2, P < 0.05). There was no significant hypometabolism in the temporal or frontal lobes. PD subjects who did not become demented (non-PDD), compared with controls, had reduced cerebral metabolism in the primary occipital cortex (BA 17) that was revealed only by 3D-SSP analysis. Follow-up scans in 5 PDD subjects at 2 y after study entry demonstrated a significant interval within-subject change in the thalamus (-11.4%), posterior cingulate (-9%), occipital (-7%), parietal (-7%), and frontal cortices (-7%) and mild reductions in the temporal cortex (-5%) and hippocampus (-3%), compared with study entry scans.
  
  
  CONCLUSIONS
  Incident dementia in idiopathic PD is heralded by decreased metabolism in the visual association (BA 18) and posterior cingulate cortices, with mild involvement also of the caudate nucleus. Two-year follow-up data from 5 PDD converters show that progression to dementia is associated with mixed subcortical and cortical changes that involve the mesiofrontal lobes also. These findings provide insights into early metabolic features of parkinsonian dementia.
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, Michigan 48109-0028, USA. nbohnen@umich.edu
authors.forename: Nicolaas I
authors.initials: NI
authors.lastname: Bohnen
authors.forename: Robert A
authors.initials: RA
authors.lastname: Koeppe
authors.forename: Satoshi
authors.initials: S
authors.lastname: Minoshima
authors.forename: Bruno
authors.initials: B
authors.lastname: Giordani
authors.forename: Roger L
authors.initials: RL
authors.lastname: Albin
authors.forename: Kirk A
authors.initials: KA
authors.lastname: Frey
authors.forename: David E
authors.initials: DE
authors.lastname: Kuhl
mesh_terms: D000328:Adult; D000368:Aged; D001923:Brain Chemistry / Q000502:physiology*; D002540:Cerebral Cortex / Q000378:metabolism; D003071:Cognition / Q000502:physiology; D015331:Cohort Studies; D003704:Dementia / Q000209:etiology* / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000150:complications* / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D019275:Radiopharmaceuticals
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005947:Glucose