Objective: To identify longitudinal patterns of beta-amyloid(Ab) accumulation in Parkinson’s disease (PD) through the use of Pittsburgh Compound B (PiB) Positron Emission Tomography imaging in participants with PD and cognitively normal controls.

Background: The aggregation of Ab in neurodegenerative disease is a widely observed phenomenon, particularly well described in Alzheimer disease. Recent evidence demonstrates that Ab brain accumulation frequently occurs in PD. Despite this, relatively little is known whether the accumulation of Ab in distinct regions relates to motor and cognitive deficits in PD, and how Ab accumulates throughout disease progression. Here we hypothesized that Ab accumulation over time in PD follows a distinct, differentiable pattern from control participants.

Method: Longitudinal change in Ab distribution was assessed in 67 participants (44 PD, 23 controls) with PiB scans repeated at varying times from each participant’s initial scan (time between scans: 5.67+/-1.93 years). Each dynamic PET image was aligned, averaged over 30-60 min and paired to the most recent structural MRI. FreeSurfer5.3-based segmentation was used to generate parametrized images using a standardized uptake value ratio (SUVR) with cerebellar gray matter as the reference region. SUVR images were corrected for partial volume effects using region-based voxelwise correction and intraregional reblurred Van-Cittert. Scans were nonlinearly aligned using FNIRT (FSL5.0.1) and blurred using a 6mm full-width half max Gaussian kernel. Clusters of significant change over time were identified using permutation testing with threshold free cluster enhancement with the FSL randomise function, accounting for duration between paired scans for each participant.

Results: PD participants demonstrated substantial increases in PiB binding between initial and follow-up scans, with clusters centered in the middle cingulate cortex and anterior striatum (familywise-error rate corrected p < 0.001). Control participants did not display any significant change over time. Notably, while no participants had dementia initially, six PD participants developed dementia between initial and follow-up scans.

Conclusion: Ab deposition in the progression of PD displays a regional profile distinct from healthy controls. How or whether the regional accumulation of Ab correlates or predicts the progression of cognitive and motor deficits remains to be tested.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/parkinsons-disease-exhibits-longitudinal-increases-in-beta-amyloid-in-the-striatum-and-cingulate-gyrus/