Striatal and Cortical -Amyloidopathy and Cognition in Parkinson's Disease

IntroductionAlthough most previous cognitive studies of -amyloidopathy in PD focused on cortical plaque deposition, recent postmortem studies point to an important role of striatal -amyloid plaque deposition. The aim of this study was to investigate the relative contributions of striatal and cortical -amyloidopathy to cognitive impairment in PD. MethodsPatients with PD (n = 62; age, 68.9 6.4 years; H & Y stage: 2.7 0.5; MoCA score: 25.2 +/- 3.0) underwent [C-11]Pittsburgh compound B -amyloid, [C-11]dihydrotetrabenazine monoaminergic, and [C-11]methyl-4-piperidinyl propionate acetylcholinesterase brain PET imaging and neuropsychological assessment. [C-11]Pittsburgh compound B -amyloid data from young to middle-aged healthy subjects were used to define elevated [C-11]Pittsburgh compound B binding in patients. ResultsElevated cortical and striatal -amyloid deposition were present in 37% and 16%, respectively, of this predominantly nondemented cohort of patients with PD. Increased striatal -amyloid deposition occurred in half of all subjects with increased cortical -amyloid deposition. In contrast, increased striatal -amyloid deposition did not occur in the absence of increased cortical -amyloid deposition. Analysis of covariance using global composite cognitive z scores as the outcome parameter showed significant regressor effects for combined striatal and cortical -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 -amyloidopathy, compared to cortical-only -amyloidopathy and non--amyloidopathy subgroups. ConclusionsThe combined presence of striatal and cortical -amyloidopathy is associated with greater cognitive impairment than cortical -amyloidopathy alone in PD. (c) 2015 International Parkinson and Movement Disorder Society