Objective: to investigate if a reduction in cortical and subcortical synaptic density measured in vivo with the synaptic vesicle protein 2A (SV2A) binding [11C] UCB-J PET tracer correlates with MPS in healthy older adults, and to investigate the influence of co-occurring white matter lesions (WML) as a marker of brain aging.

Background: Introduction: normal aging is associated with a decline in the quality and quantity of movement, often considered as “mild parkinsonian signs” (MPS) [1]. Although not pathological per se, MPS increase a person’s risk for Parkinson’s disease, dementia and early mortality. How MPS can be distinguished from parkinsonism in the early stages of neurodegenerative movement disorders, and whether MPS are a consequence of global brain aging or a specific dysfunction in brain motor circuitry is unresolved.

Method: we included 59 healthy adults aged 50 years or older, from 2 case-control cohort studies at the University Hospitals Leuven [2, 3]. Both brain MRI (3D T1, FLAIR) and [11C] UCB-J PET data were available in 53 participants. Partial volume correction using the region-based-voxel-wise method was applied to the PET data. We conducted a region of interest (ROI) based analysis that included the frontal, parietal, temporal and occipital lobes as cortical ROI, the caudate nuclei, putamen, accumbens nuclei and thalami as subcortical ROI, and the cerebellum. Multiple linear regression analysis was performed with the MDS-UPDRS III score as the dependent variable measuring parkinsonian signs and mean [11C] UCB-J PET in each ROI (unilateral), with age, Fazekas score (global WML burden) and cohort as covariates (Bonferroni correction p<0.005).

Results: Participants (mean age 68 ±7.5 yrs.; 49% female) had an average MDS-UPDRS III score of 3.4 ± 2.8 Lower synaptic density in cortical regions (frontal, parietal, occipital, temporal lobes), subcortical gray matter regions (caudate nuclei and thalami) and in the cerebellum was associated with MDS-UPDRS III score. Cohen’s f2 showed large effect sizes for regression models with subcortical (range 0.49-0.60), cortical structures (range 0.51-0.71) and the cerebellum (0.59). Fazekas score was not associated with MPS.

Conclusion: mild parkinsonian signs in healthy aging are associated with lower synaptic density throughout the brain, independent of white matter lesion load.

References: 1. Buchanan SM, Richards M, Schott JM, Schrag A. Mild Parkinsonian Signs: A Systematic Review of Clinical, Imaging, and Pathological Associations. Mov Disord. 2021 Nov;36(11):2481-2493.
2. Delva A, Van Weehaeghe D, Koole M, Van Laere K, Vandenberghe W. Loss of Presynaptic Terminal Integrity in the Substantia Nigra in Early Parkinson’s Disease. Mov Disord. 2020 Nov;35(11):1977-1986.
3. Emsell L, Laroy M, Van Cauwenberge M, Vande Casteele T, Vansteelandt K, Van Laere K, Sunaert S, Van den Stock J, Bouckaert F, Vandenbulcke M. The Leuven late life depression (L3D) study: PET-MRI biomarkers of pathological brain ageing in late-life depression: study protocol. BMC Psychiatry. 2021 Jan 28;21(1):64.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/synaptic-density-in-cortical-and-subcortical-gray-matter-is-associated-with-mild-parkinsonian-signs-mps-in-healthy-older-adults-a-11c-ucb-j-pet-study/