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

Introduction: 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 [¹¹C]Pittsburgh compound B β-amyloid, [¹¹C]dihydrotetrabenazine monoaminergic, and [¹¹C]methyl-4-piperidinyl propionate acetylcholinesterase brain PET imaging and neuropsychological assessment. [¹¹C]Pittsburgh compound B β-amyloid data from young to middle-aged healthy subjects were used to define elevated [¹¹C]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.