title: Cognitive correlates of cortical cholinergic denervation in Parkinson's disease and parkinsonian dementia.
abstract: We recently reported findings that loss of cortical acetylcholinesterase (AChE) activity is greater in parkinsonian dementia than in Alzheimer's disease (AD). In this study we determined cognitive correlates of in vivo cortical AChE activity in patients with parkinsonian dementia (PDem, n = 11), Parkinson's disease without dementia (PD, n = 13), and in normal controls (NC, n = 14) using N-[(11)C]methyl-piperidin-4-yl propionate ([(11)C]PMP) AChE positron emission tomography (PET). Cortical AChE activity was significantly reduced in the PDem (-20.9%) and PD (-12.7 %) subjects (P < 0.001) when compared with the control subjects. Analysis of the cognitive data within the patient groups demonstrated that scores on the WAIS-III Digit Span, a test of working memory and attention, had most robust correlation with cortical AChE activity (R = 0.61, p < 0.005). There were also significant correlations between cortical AChE activity and other tests of attentional and executive functions, such as the Trail Making and Stroop Color Word tests. There was no significant correlation between cortical AChE activity and duration of motor disease (R = -0.01, ns) or severity of parkinsonian motor symptoms (R = 0.14, ns). We conclude that cortical cholinergic denervation in PD and parkinsonian dementia is associated with decreased performance on tests of attentional and executive functioning.
authors.affiliation: Department of Radiology, University of Pittsburgh Medical School, PA 15213, USA. nbohnen@pitt.edu
authors.forename: N I
authors.initials: NI
authors.lastname: Bohnen
authors.forename: D I
authors.initials: DI
authors.lastname: Kaufer
authors.forename: R
authors.initials: R
authors.lastname: Hendrickson
authors.forename: L S
authors.initials: LS
authors.lastname: Ivanco
authors.forename: B J
authors.initials: BJ
authors.lastname: Lopresti
authors.forename: G M
authors.initials: GM
authors.lastname: Constantine
authors.forename: Ch A
authors.initials: ChA
authors.lastname: Mathis
authors.forename: J G
authors.initials: JG
authors.lastname: Davis
authors.forename: R Y
authors.initials: RY
authors.lastname: Moore
authors.forename: S T
authors.initials: ST
authors.lastname: Dekosky
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D003071:Cognition / Q000502:physiology*; D003704:Dementia / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D003714:Denervation; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008570:Memory, Short-Term / Q000502:physiology; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D010300:Parkinson Disease / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D049268:Positron-Emission Tomography / Q000379:methods; D011422:Propionates / Q000493:pharmacokinetics
chemical_list: D002250:Carbon Radioisotopes; D011422:Propionates; D000110:Acetylcholinesterase