Findings from a new study presented at MDS 2024 suggest that variations in cholinergic denervation patterns may hold promise for differentiating Parkinson disease and progressive supranuclear palsy with parkinsonism.
Prabesh Kanel, MS, PhD
(Credit: University of Michigan)
In a new study, findings demonstrated a decreased cholinergic transporter binding, especially in the regions of midbrain, pons, and occipital lobes, among patients with Parkinson disease (PD) compared with patients with progressive supranuclear palsy with parkinsonism (PSP-P). These results suggest that these differing cholinergic denervation patterns could pave way for earlier diagnoses, improved treatment strategies, and enhanced patient outcomes for both diseases although larger cohorts may be needed to further understand these differences.1
A voxel-based analysis using a 2-sample t-test among 107 patients with PD (men, n = 83; women, n = 24; age, 68.05 [±7.65]; disease duration, 6.50 [±4.31]; HY, 2.60 [±0.74]) and 5 patients with PSP-P (men, n = 3; women, n = 2; age, 66.00 [±8.22]; disease duration, 5.680 [±6.50]; HY, 2.70 [±1.20]) displayed distinct patterns of vesicular acetylcholine transporter (VAChT) binding in both groups. In comparison with participants who had PSP-P, patients with PD showed reduced VAChT binding in several brain regions, such as the midbrain, pons, bilateral superior temporal lobes, bilateral occipital lobes, ventral anterior nucleus of the thalamus, and the left mid cingulate cortex.
Presented at the 2024 International Congress of Parkinson’s Disease and Movement Disorders, held September 27 to October 1, in Philadelphia, Pennsylvania, by lead author Prabesh Kanel, MS, PhD, a research assistant professor of radiology at University of Michigan, investigators used a highly selective radiotracer in patients with PD and patients with PSP-P to assess VAChT [18F]- fluoroethoxybenzovesamicol (18F-FEOBV) PET and MRI. Researchers then performed whole brain voxel-based 2-sample t-test analysis to identify clusters of spatially contiguous voxels that are statistically significant (P <.01).
Previous research has demonstrated that PSP-P and PD pose challenges for providers in early distinction, where these diseases often fall into the realm of differential diagnosis. Further studies have revealed that biomarkers have aided clinicians to distinguish between these 2 related but also distinct neurodegenerative diseases at the onset. In a prior study, findings showed impairment of the cholinergic system in both patients with PSP and individuals with PD,2 albeit impacting distinct regions; however, before the presented study at MDS 2024, there was limited focus on the PSP-P subtype compared with PD.
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In the previous study, published in the Journal of Neural Transmission, researchers assessed the differential cholinergic systems changes in PSP (n = 8) compared with PD (n = 107) and older controls (n = 19) utilizing a vesicular acetylcholine transporter [18F]-FEOBV PET. Conducted by lead author Kanel and colleagues, the study also used a Statistical Parametric Mapping software for inter-group comparisons with parametric [18F]-FEOBV DVR images in a whole-brain voxel-based PET analysis.
Findings in the prior study voxel-based analyses displayed a reduced FEOBV binding in the tectum, metathalamus, epithalamus, pulvinar, bilateral frontal opercula, anterior insulae, superior temporal pole, anterior cingulum, some striatal subregions, lower brainstem, and cerebellum in PSP compared with PD (P <.05; false discovery rate-corrected). Results also showed more severe and diffuse reductions present in PSP versus the controls.
Additional results showed higher frequency of midbrain cholinergic losses observed by researchers in PSP compared with the participants who had PD using 5th percentile normative cut-off values (χ2 = 4.12; P <.05). In the comparison with PD, authors noted that these findings suggested disease-specific cholinergic vulnerability in the tectum, striatal cholinergic interneurons, and projections from the pedunculopontine nucleus, medial vestibular nucleus, and the cholinergic forebrain in PSP.2
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