Quantification of Brain β-Amyloid Load in Parkinson's Disease With Mild Cognitive Impairment: A PET/MRI Study

Background: Mild cognitive impairment in Parkinson's disease (PD-MCI) is associated with faster cognitive decline and conversion to dementia. There is uncertainty about the role of beta-amyloid (A beta) co-pathology and its contribution to the variability in PD-MCI profile and cognitive progression. Objective: To study how presence of A beta affects clinical and cognitive manifestations as well as regional brain volumes in PD-MCI. Methods: Twenty-five PD-MCI patients underwent simultaneous PET/3T-MRI with [F-18]flutemetamol and a clinical and neuropsychological examination allowing level II diagnosis. We tested pairwise differences in motor, clinical, and cognitive features with Mann-Whitney U test. We calculated [F-18]flutemetamol (FMM) standardized uptake value ratios (SUVR) in striatal and cortical ROIs, and we performed a univariate linear regression analysis between the affected cognitive domains and the mean SUVR. Finally, we investigated differences in cortical and subcortical brain regional volumes with magnetic resonance imaging (MRI). Results: There were 8 A beta+ and 17 A beta- PD-MCI. They did not differ for age, disease duration, clinical, motor, behavioral, and global cognition scores. PD-MCI-A beta+ showed worse performance in the overall executive domain (p = 0.037). Subcortical ROIs analysis showed significant A beta deposition in PD-MCI-A beta+ patients in the right caudal and rostral middle frontal cortex, in precuneus, in left paracentral and pars triangularis (p < 0.0001), and bilaterally in the putamen (p = 0.038). Cortical regions with higher amyloid load correlated with worse executive performances (p < 0.05). Voxel-based morphometry (VBM) analyses showed no between groups differences. Conclusions: Presence of cerebral A beta worsens executive functions, but not motor and global cognitive abilities in PD-MCI, and it is not associated with middle-temporal cortex atrophy. These findings, together with the observation of significant proportion of PD-MCI-A beta-, suggest that A beta may not be the main pathogenetic determinant of cognitive deterioration in PD-MCI, but it would rather aggravate deficits in domains vulnerable to Parkinson primary pathology.

Automated summary

This study investigated the impact of beta-amyloid (Aβ) on the clinical and cognitive manifestations as well as regional brain volumes in Parkinson's disease with mild cognitive impairment (PD-MCI). The results showed that the presence of Aβ worsened executive functions in PD-MCI patients, but did not affect motor and global cognitive abilities. Aβ deposition was found in specific brain regions, and higher amyloid load correlated with worse executive performances. However, Aβ may not be the main cause of cognitive deterioration in PD-MCI.