Abstract
BackgroundMild 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.ObjectiveTo study how presence of Aβ affects clinical and cognitive manifestations as well as regional brain volumes in PD-MCI.MethodsTwenty-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).ResultsThere 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.ConclusionsPresence 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.
Highlights
Cognitive alterations in Parkinson’s disease (PD) are among the most disabling non-motor symptoms, and they impact negatively on patient’s and caregiver’s quality of life and can be present already in early stages of disease
In a recent PET/Magnetic resonance imaging (MRI) study [18] in cognitively wellcharacterized Lewy Body disease (LBD) patients, we observed an integral role of brain amyloidosis in cognitive profile and progression, affecting mainly global cognition (MoCA, MMSE), attentive/executive, and semantic recall abilities
Regarding genetic variability as a possible confounding factor, we excluded from this study subjects carrying known PD genetic mutations and variants, but we did not screen for apolipoprotein E (APOE) ε4
Summary
Cognitive alterations in Parkinson’s disease (PD) are among the most disabling non-motor symptoms, and they impact negatively on patient’s and caregiver’s quality of life and can be present already in early stages of disease. Some studies have suggested contribution of Aβ cortical and subcortical depositions to cognitive decline in PD in association with attentive and executive deficits, while others indicated an increased risk of dementia in the late disease stages [8–13]. These differences may be related to the heterogeneous methodology adopted including variability in age and sex as well as poorly characterized cognitive diagnosis in relatively small cohorts [11, 14–17]. In a recent PET/MRI study [18] in cognitively wellcharacterized Lewy Body disease (LBD) patients, we observed an integral role of brain amyloidosis in cognitive profile and progression, affecting mainly global cognition (MoCA, MMSE), attentive/executive, and semantic recall abilities. 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
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
