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Abstract Details

Limbic Posterior, Peri-Central, and Paralimbic Cortical Cholinergic Losses Predict Cognitive Changes in Parkinson Disease: A Two-Year Longitudinal [18F]-FEOBV PET Study
Aging, Dementia, Cognitive, and Behavioral Neurology
ES1 - Emerging Science 1 (11:39 AM-11:45 AM)
005

Dementia is a debilitating non-motor complication of PD affecting most patients with advancing disease. Post-mortem studies revealed prominent cholinergic neuron loss in the basal forebrain in PD patients with dementia. Cross-sectional brain imaging studies showed evidence of prominent cholinergic terminal deficits in posterior cortical brain regions in non-demented patients. Longitudinal studies are sparse, small in sample size, and use less specific proxy cholinergic markers not directly targeting nerve terminals. VAChT PET ligands are spatially resolute and allow reliable quantification in high-binding areas of the brain compared to prior generation PET ligands.

To apply statistical parametric mapping (SPM) whole brain voxel-based analysis of [18F]-fluoroethoxybenzovesamicol (FEOBV) vesicular acetylcholine transporter (VAChT) brain PET to predict 2-year cognitive changes in Parkinson disease (PD).

77 PD participants underwent baseline brain VAChT [18F]-FEOBV PET, MRI imaging and completed a comprehensive neuropsychological test battery at baseline and at two-year follow up. Percent differences between baseline and follow-up global composite cognitive Z-scores were used to identify longitudinal cognitive changes, with negative scores indicating decline and positive scores indicating no evidence of decline. SPM12 whole brain voxel-regression analysis was performed to identify statistically significant clusters of spatially contiguous voxels correlating with global cognitive decline.

Our analysis showed baseline reduced VAChT binding of the mid to posterior cingulum, precuneus, parietal-lateral occipital, right more the left superior temporal, insula, opercular, right more than left precentral and postcentral gyrus, and insulae (cluster-FDR adjusted significant at p <0.05) predicting cognitive decline.

This is the first longitudinal, large scale cholinergic PET study showing that limbic posterior brain (cingulum), peri-central cortices, and paralimbic cortices are an early predictor of cognitive decline in PD. These findings may augur novel studies targeting specific posterior limbic, primary sensorimotor and paralimbic circuitry to treat cognitive decline in PD.

Authors/Disclosures
Taylor Brown
PRESENTER
Miss Brown has nothing to disclose.
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
Roger Albin (University of Michigan) Dr. Albin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda. Dr. Albin has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Albin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Albin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Vaccinex. The institution of Dr. Albin has received research support from NIH-NINDS. The institution of Dr. Albin has received research support from Parkinson's Foundation. The institution of Dr. Albin has received research support from Michael J. Fox Foundation. Dr. Albin has received personal compensation in the range of $5,000-$9,999 for serving as a Grant Application Reivewer with Michael J. Fox Foundation.
No disclosure on file
No disclosure on file
Nicolaas Bohnen (University of Michigan) Dr. Bohnen has stock in Delta. The institution of Dr. Bohnen has received research support from NIH. The institution of Dr. Bohnen has received research support from VA. Dr. Bohnen has received research support from NIH. The institution of Dr. Bohnen has received research support from Parkinson fnd.