Journal Article

Beta amyloid deposition and cognitive decline in Parkinson’s disease: a study of the PPMI cohort

Mihaescu, Alexander S., Valli, Mikaeel, Masellis, Mario, Diez-Cirarda, Maria, Strafella, Antonio P., Uribe, Carme, Graff-Guerrero, Ariel

2022

Overview

The accumulation of beta amyloid in the brain has a complex and poorly understood impact on the progression of Parkinson’s disease pathology and much controversy remains regarding its role, specifically in cognitive decline symptoms. Some studies have found increased beta amyloid burden is associated with worsening cognitive impairment in Parkinson’s disease, especially in cases where dementia occurs, while other studies failed to replicate this finding. To better understand this relationship, we examined a cohort of 25 idiopathic Parkinson’s disease patients and 30 healthy controls from the Parkinson’s Progression Marker Initiative database. These participants underwent [ 18 F]Florbetaben positron emission tomography scans to quantify beta amyloid deposition in 20 cortical regions. We then analyzed this beta amyloid data alongside the longitudinal Montreal Cognitive Assessment scores across 3 years to see how participant’s baseline beta amyloid levels affected their cognitive scores prospectively. The first analysis we performed with these data was a hierarchical cluster analysis to help identify brain regions that shared similarity. We found that beta amyloid clusters differently in Parkinson’s disease patients compared to healthy controls. In the Parkinson’s disease group, increased beta amyloid burden in cluster 2 was associated with worse cognitive ability, compared to deposition in clusters 1 or 3. We also performed a stepwise linear regression where we found an adjusted R 2 of 0.495 (49.5%) in a model explaining the Parkinson’s disease group’s Montreal Cognitive Assessment score 1-year post-scan, encompassing the left gyrus rectus, the left anterior cingulate cortex, and the right parietal cortex. Taken together, these results suggest regional beta amyloid deposition alone has a moderate effect on predicting future cognitive decline in Parkinson’s disease patients. The patchwork effect of beta amyloid deposition on cognitive ability may be part of what separates cognitive impairment from cognitive sparing in Parkinson’s disease. Thus, we suggest it would be more useful to measure beta amyloid burden in specific brain regions rather than using a whole-brain global beta amyloid composite score and use this information as a tool for determining which Parkinson’s disease patients are most at risk for future cognitive decline.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: [18F]Florbetaben / Alzheimer's disease / Beta amyloid / Biomedical and Life Sciences / Biomedicine / Brain / Cognitive ability / Cognitive decline / Cortex (cingulate) / Cortex (parietal) / Dementia / Dementia disorders / Development and progression / Disease susceptibility / Kinases / Medical research / Medicine, Experimental / Movement disorders / Neurodegenerative diseases / Neurology / Neuropsychology / Neurosciences / Neurotoxicity / Parkinson's disease / PET imaging / Positron emission tomography / PPMI / Psychopharmacology / β-Amyloid