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

Michela Garon; Luca Weis; Eleonora Fiorenzato; Francesca Pistonesi; Annachiara Cagnin; Alessandra Bertoldo; Mariagiulia Anglani; Diego Cecchin; Angelo Antonini; Roberta Biundo

doi:10.3389/fneur.2021.760518

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

Front Neurol. 2022 Mar 1:12:760518. doi: 10.3389/fneur.2021.760518. eCollection 2021.

Authors

Michela Garon¹, Luca Weis¹, Eleonora Fiorenzato², Francesca Pistonesi¹, Annachiara Cagnin^{3

4}, Alessandra Bertoldo^{4

5}, Mariagiulia Anglani⁶, Diego Cecchin^{4

7}, Angelo Antonini^{1

4

8}, Roberta Biundo^{2

8}

Affiliations

¹ Parkinson and Movement Disorders Unit, Department of Neuroscience, University of Padua, Padua, Italy.
² Department of General Psychology, University of Padua, Padua, Italy.
³ Department of Neuroscience, University of Padua, Padua, Italy.
⁴ Padova Neuroscience Center, University of Padua, Padua, Italy.
⁵ Department of Information Engineering, University of Padua, Padua, Italy.
⁶ Neuroradiology Unit, Padua University Hospital, Padua, Italy.
⁷ Nuclear Medicine Unit, Department of Medicine - DIMED, Padua University Hospital, Padua, Italy.
⁸ Study Center for Neurodegeneration, University of Padua, Padua, Italy.

Abstract

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 β-amyloid (Aβ) co-pathology and its contribution to the variability in PD-MCI profile and cognitive progression.

Objective: To study how presence of Aβ 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 [¹⁸F]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 [¹⁸F]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 Aβ+ and 17 Aβ- PD-MCI. They did not differ for age, disease duration, clinical, motor, behavioral, and global cognition scores. PD-MCI-Aβ+ showed worse performance in the overall executive domain (p = 0.037). Subcortical ROIs analysis showed significant Aβ deposition in PD-MCI-Aβ+ 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 Aβ 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-Aβ-, suggest that Aβ 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.

Keywords: PET; Parkinson's disease; amyloid-β; atrophy; cognition; dementia; executive functions; mild cognitive impairment.