| Title: |
Cortical α4β2-nicotinic acetylcholine receptors and cognitive decline in Parkinson's disease |
| Authors: |
Mills, Kelly A; Kuwabara, Hiroto; Du, Yong; Gomez, Gabriela; Motley, Chelsie S; Skorobogatova, Yana; Spiro, Ergi; Coughlin, Jennifer M; Lesniak, Wojciech; Brandt, Jason; Kamath, Vidya; Pomper, Martin G; Smith, Gwenn S |
| Contributors: |
National Institute of Neurological Disorders and Stroke; National Center for Advancing Translational Sciences; School of Medicine, Johns Hopkins University |
| Source: |
Journal of Parkinson’s Disease ; volume 15, issue 2, page 374-386 ; ISSN 1877-7171 1877-718X |
| Publisher Information: |
SAGE Publications |
| Publication Year: |
2025 |
| Description: |
Background Autopsy and in vivo molecular imaging studies suggest altered binding of the α4β2-nicotinic cholinergic receptor (α4β2-nAChR) with cognitive dysfunction in Parkinson's disease (PD). Objective To determine the relationship between cortical and hippocampal binding of the α4β2-nAChR with [ 18 F]XTRA PET, a high-affinity radiotracer that enables quantification of α4β2-nAChR in these regions, and cognitive function in individuals with PD. Methods Individuals with PD (N = 32) and age-similar, controls without PD or dementia (N = 10) completed a cognitive assessment and one 90-min, [ 18 F]XTRA PET scan. Metabolite-corrected arterial input function radioactivity time-activity curves were generated to obtain total distribution volume (V T ) across 12 regions of interest (ROIs). [ 18 F]XTRA binding was compared 1) between controls and people with PD and 2) between controls, persons with PD with normal cognition (PD-NC), and persons with PD with MCI (PD-MCI). Results [ 18 F]XTRA binding was higher in the occipital cortex of the combined group of PD participants compared to age-similar controls. No regions showed lower binding in PD. V T with, but not without, partial volume correction was different between controls, PD-NC, and PD-MCI groups, and this was driven by higher binding in PD-MCI compared to controls. Regression of regional V T on cognitive domain T-scores, adjusting for age, showed that worse performance in visual-spatial memory tasks was associated with higher V T in the precuneus and the entire parietal cortex. Conclusions Higher α4β2-nAChR binding in posterior cortical regions is found in PD and associated with worse visual perception and memory, possibly due to lower receptor occupancy by endogenous acetylcholine. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1177/1877718x241313373 |
| DOI: |
10.1177/1877718X241313373 |
| Availability: |
https://doi.org/10.1177/1877718x241313373; https://journals.sagepub.com/doi/pdf/10.1177/1877718X241313373; https://journals.sagepub.com/doi/full-xml/10.1177/1877718X241313373 |
| Rights: |
https://creativecommons.org/licenses/by-nc/4.0/ ; https://journals.sagepub.com/page/policies/text-and-data-mining-license |
| Accession Number: |
edsbas.DBF7C295 |
| Database: |
BASE |