title: Heterogeneity of cholinergic denervation in Parkinson's disease without dementia.
abstract: Parkinson's disease (PD) is a multisystem neurodegenerative disorder. Heterogeneous clinical features may reflect heterogeneous changes in different brain regions. In contrast to the pronounced nigrostriatal denervation characteristic of PD, cholinergic changes are less marked. We investigated cholinergic innervation activity in PD subjects relative to normal subjects. Nondemented PD subjects (n=101, age 65.3±7.2 years) and normal subjects (n=29, age 66.8±10.9 years) underwent clinical assessment and [(11)C]methyl-4-piperidinyl propionate acetylcholinesterase and [(11)C]dihydrotetrabenazine monoaminergic positron emission tomography (PET) imaging. Cholinergic projection changes were heterogeneous for 65 out of 101 PD subjects who had neocortical and thalamic acetylcholinesterase activity within the normal range. The remainder had combined neocortical and thalamic (13/101), isolated neocortical (18/101), or isolated thalamic (5/101) acetylcholinesterase activity below the normal range. The low neocortical acetylcholinesterase activity subgroup had significantly lower global cognitive performance compared with the normal range subgroup (F=7.64, P=0.0069) with an independent effect for nigrostriatal denervation (F=7.60, P=0.0074). The low thalamic acetylcholinesterase activity subgroup did not differ from the normal thalamic acetylcholinesterase activity subgroup in cognitive performance or motor impairments except for a history of falls (P=0.0023). Cholinergic denervation is heterogeneous with reduced neocortical and/or thalamic acetylcholinesterase activity in 36% of nondemented PD subjects with corresponding clinical phenotypic variation. Results also show independent cognitive effects for both cholinergic and dopaminergic system changes in nondemented PD subjects.
authors.affiliation: Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, Michigan 48105-9755, USA. nbohnen@umich.edu
authors.forename: Nicolaas I
authors.initials: NI
authors.lastname: Bohnen
authors.forename: Martijn L T M
authors.initials: ML
authors.lastname: Müller
authors.forename: Vikas
authors.initials: V
authors.lastname: Kotagal
authors.forename: Robert A
authors.initials: RA
authors.lastname: Koeppe
authors.forename: Michael R
authors.initials: MR
authors.lastname: Kilbourn
authors.forename: Sid
authors.initials: S
authors.lastname: Gilman
authors.forename: Roger L
authors.initials: RL
authors.lastname: Albin
authors.forename: Kirk A
authors.initials: KA
authors.lastname: Frey
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D002250:Carbon Radioisotopes; D003071:Cognition / Q000502:physiology*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000201:enzymology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000502:physiology; D019579:Neocortex / Q000000981:diagnostic imaging / Q000201:enzymology*; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000523:psychology; D049268:Positron-Emission Tomography; D011422:Propionates / Q000378:metabolism; D013747:Tetrabenazine / Q000031:analogs & derivatives / Q000378:metabolism; D013788:Thalamus / Q000000981:diagnostic imaging / Q000201:enzymology*
chemical_list: D002250:Carbon Radioisotopes; D011422:Propionates; C032811:dihydrotetrabenazine; C099183:N-methylpiperidin-4-yl propionate; D000110:Acetylcholinesterase; D013747:Tetrabenazine