title: Striatal and Cortical β-Amyloidopathy and Cognition in Parkinson's Disease.
abstract: BACKGROUND
  Although most previous cognitive studies of β-amyloidopathy in PD focused on cortical plaque deposition, recent postmortem studies point to an important role of striatal β-amyloid plaque deposition. The aim of this study was to investigate the relative contributions of striatal and cortical β-amyloidopathy to cognitive impairment in PD.
  
  
  METHODS
  Patients with PD (n = 62; age, 68.9 ± 6.4 years; H & Y stage: 2.7 ± 0.5; MoCA score: 25.2 ± 3.0) underwent [(11) C]Pittsburgh compound B β-amyloid, [(11) C]dihydrotetrabenazine monoaminergic, and [(11) C]methyl-4-piperidinyl propionate acetylcholinesterase brain PET imaging and neuropsychological assessment. [(11) C]Pittsburgh compound B β-amyloid data from young to middle-aged healthy subjects were used to define elevated [(11) C]Pittsburgh compound B binding in patients.
  
  
  RESULTS
  Elevated cortical and striatal β-amyloid deposition were present in 37% and 16%, respectively, of this predominantly nondemented cohort of patients with PD. Increased striatal β-amyloid deposition occurred in half of all subjects with increased cortical β-amyloid deposition. In contrast, increased striatal β-amyloid deposition did not occur in the absence of increased cortical β-amyloid deposition. Analysis of covariance using global composite cognitive z scores as the outcome parameter showed significant regressor effects for combined striatal and cortical β-amyloidopathy (F = 4.18; P = 0.02) after adjusting for covariate effects of cortical cholinergic activity (F = 5.67; P = 0.02), caudate nucleus monoaminergic binding, duration of disease, and age (total model: F = 3.55; P = 0.0048). Post-hoc analysis showed significantly lower cognitive z score for combined striatal and cortical β-amyloidopathy, compared to cortical-only β-amyloidopathy and non-β-amyloidopathy subgroups.
  
  
  CONCLUSIONS
  The combined presence of striatal and cortical β-amyloidopathy is associated with greater cognitive impairment than cortical β-amyloidopathy alone in PD.
authors.affiliation: Department of Radiology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Neha
authors.initials: N
authors.lastname: Shah
authors.affiliation: Department of Radiology, University of Michigan, Ann Arbor, Michigan, USA.|Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Kirk A
authors.initials: KA
authors.lastname: Frey
authors.affiliation: Department of Radiology, University of Michigan, Ann Arbor, Michigan, USA.|University of Michigan Morris K. Udall Center, Ann Arbor, Michigan, USA.
authors.forename: Martijn L T M
authors.initials: ML
authors.lastname: Müller
authors.affiliation: Department of Radiology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Myria
authors.initials: M
authors.lastname: Petrou
authors.affiliation: Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Vikas
authors.initials: V
authors.lastname: Kotagal
authors.affiliation: Department of Radiology, University of Michigan, Ann Arbor, Michigan, USA.|University of Michigan Morris K. Udall Center, Ann Arbor, Michigan, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Koeppe
authors.affiliation: Department of Radiology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Peter J H
authors.initials: PJ
authors.lastname: Scott
authors.affiliation: Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.|Neurology Service and GRECC, VAAAHS, Ann Arbor, Michigan, USA.|University of Michigan Morris K. Udall Center, Ann Arbor, Michigan, USA.
authors.forename: Roger L
authors.initials: RL
authors.lastname: Albin
authors.affiliation: Department of Radiology, University of Michigan, Ann Arbor, Michigan, USA.|Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.|Neurology Service and GRECC, VAAAHS, Ann Arbor, Michigan, USA.|University of Michigan Morris K. Udall Center, Ann Arbor, Michigan, USA.
authors.forename: Nicolaas I
authors.initials: NI
authors.lastname: Bohnen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000704:Analysis of Variance; D000814:Aniline Compounds / Q000493:pharmacokinetics; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D002540:Cerebral Cortex / Q000378:metabolism*; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology*; D003342:Corpus Striatum / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications* / Q000000981:diagnostic imaging; D049268:Positron-Emission Tomography; D013747:Tetrabenazine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D013844:Thiazoles / Q000493:pharmacokinetics
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D002247:Carbon Isotopes; D013844:Thiazoles; C032811:dihydrotetrabenazine; D013747:Tetrabenazine
keywords: PET; Parkinson's disease; acetylcholinesterase; cognitive impairment; cortex; dopamine; striatum; β-amyloid