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

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.

Machine learning can predict mild cognitive impairment in Parkinson's disease

“…While comparing β-amyloid load in the subgroup of PD-MCI vs. noPD-MCI, we failed to find any significant difference in all examined cortical and subcortical areas. Indeed, our findings are consistent with recent research that equally did not support an association between increased Aβ deposition and cognitive decline in PD ( 17 , 18 , 44 ). It is worth noting that we compared the two groups on averaged SUVs evaluating β-amyloid load as continuous variables, being the main aim of the present study to use amyloid PET measures as continuous features implementing machine learning models.…”

“…Besides mental symptoms, a growing body of evidence indicates the association between cognitive decline and several gait and balance dysfunction, including the postural instability gait difficulty (PIGD) phenotype ( 7 , 8 ), freezing of gait (FOG) ( 9 – 11 ), and specific walking alterations, especially in dual-task conditions, on quantitative gait evaluations ( 12 – 16 ). In addition, although the evidence consistently suggests that low cerebrospinal fluid levels of amyloid-β42, a marker of Alzheimer's disease (AD), may predict future cognitive decline and PDD ( 5 ), to date, amyloid-β (Aβ) Positron Emission Tomography (PET) imaging studies have reported conflicting results ( 17 – 21 ), thus failing to consistently demonstrate an association between Aβ plaques deposition and cognitive dysfunction in PD. Of note, many cross-sectional studies showed a relationship between Aβ pathology and the PIGD subtype in PD ( 22 – 25 ).…”

Research Evidence of the Role of the Glymphatic System and Its Potential Pharmacological Modulation in Neurodegenerative Diseases

“…Aβ retention can also be present in a minority of PD patients [ 70 ]. A recent 3-year longitudinal study [ 71 ] found that PD patients with enlarged Basal Ganglia PVS (BG-PVS) at baseline had reduced CSF Aβ 42 and had lower Montreal cognitive assessment (MoCA) scores at follow-up compared to PD patients without enlarged BG-PVS.…”

“…A recent 3-year longitudinal study [ 71 ] found that PD patients with enlarged Basal Ganglia PVS (BG-PVS) at baseline had reduced CSF Aβ 42 and had lower Montreal cognitive assessment (MoCA) scores at follow-up compared to PD patients without enlarged BG-PVS. However, several studies have shown a low prevalence of Aβ with PD without dementia [ 72 ] and those with MCI [ 70 ]. In a study utilising Positron Emission Tomography (PET) imaging with [ 18 F]Florbetaben in a large cohort of PD subjects (ranging from PD patients with normal cognition to subjects with MCI to Parkinson’s Disease Dementia), increasing age was associated with increased cortical [ 18 F]Florbetaben retention in the PD group.…”

“…However, after adjusting for age, no correlation was found between cortical [ 18 F]Florbetaben uptake and global cognitive ability within the PD cohort [ 73 ]. Results from these studies suggest that Aβ accumulation is not the primary cause of cognitive impairment in PD, rather the presence of Aβ synergises with the other pathological processes, which can accelerate primary cognitive impairment seen in PD [ 70 , 73 ]. At the time of this review, no specific studies have explored Aβ changes specifically within the glymphatic system of PD patients.…”