title: Cerebral cortical and subcortical cholinergic deficits in parkinsonian syndromes.
abstract: OBJECTIVE
  Cholinergic projections to cerebral cortical and subcortical regions are decreased in Parkinson disease (PD), but not evaluated in the parkinsonian syndromes of multiple system atrophy (MSA-P) and progressive supranuclear palsy (PSP). We studied cholinergic innervation in these disorders as compared to age-appropriate normal control subjects.
  
  
  METHODS
  We used PET with [(11)C]PMP to measure acetylcholinesterase (AChE) activity in multiple cerebral cortical and subcortical regions. We studied 22 normal controls, 12 patients with PD, 13 patients with MSA-P, and 4 patients with PSP.
  
  
  RESULTS
  We found significantly decreased AChE activity in most cerebral cortical regions in PD and MSA-P, and a similar but nonsignificant decrease in PSP. No differences were found between PD and MSA-P. Significantly decreased AChE activity was found in PD in striatum, cerebellum, and thalamus, with a marginally significant decrease in mesencephalon and no change in pons. Significantly greater declines in AChE activity in all subcortical regions were seen in MSA-P and PSP vs in PD. Decreased AChE activity in brainstem and cerebellum of all 3 disorders correlated with disturbances of balance and gait.
  
  
  CONCLUSIONS
  Cerebral cortical cholinergic activity is decreased to a similar level in Parkinson disease (PD), parkinsonian syndromes of multiple system atrophy (MSA-P), and progressive supranuclear palsy (PSP) as compared to normal controls. Subcortical cholinergic activity is significantly more decreased in MSA-P and PSP than in PD. The more substantial decrease reflects greater impairment in the pontine cholinergic group, which is important in motor activity, particularly gait. These differences may account for the greater gait disturbances in the early stages of MSA-P and PSP than in PD.
authors.affiliation: Department of Neurology, University of Michigan Health System, Ann Arbor, USA. sgilman@med.umich.edu
authors.forename: S
authors.initials: S
authors.lastname: Gilman
authors.forename: R A
authors.initials: RA
authors.lastname: Koeppe
authors.forename: B
authors.initials: B
authors.lastname: Nan
authors.forename: C-N
authors.initials: CN
authors.lastname: Wang
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: L
authors.initials: L
authors.lastname: Junck
authors.forename: R D
authors.initials: RD
authors.lastname: Chervin
authors.forename: F
authors.initials: F
authors.lastname: Consens
authors.forename: A
authors.initials: A
authors.lastname: Bhaumik
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000033:anatomy & histology / Q000201:enzymology / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology*; D009434:Neural Pathways / Q000033:anatomy & histology / Q000473:pathology / Q000502:physiology / Q000503:physiopathology; D020734:Parkinsonian Disorders / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology*; D049268:Positron-Emission Tomography; D011849:Radioactive Tracers; D013494:Supranuclear Palsy, Progressive / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology*
chemical_list: D011849:Radioactive Tracers; D000110:Acetylcholinesterase; D000109:Acetylcholine