Abstract Details

Title Gender Differences in Dopaminergic and Cholinergic Integrity in Parkinson Disease

Topic Movement Disorders

Presentation(s) P06 - (-)

Poster/Presentation
Number 080

Objective

Background BACKGROUND: Motor and non-motor features of Parkinson disease (PD) vary between men and women though the factors that underlie these differences are not well understood. While dopaminergic denervation in the posterior putamen is thought to occur near universally in PD, loss of dopamine terminals in the caudate nucleus and loss of cholinergic terminals in the neorcortex and thalamus occur more variably. Differences in regional dopaminergic and cholinergic denervation may contribute towards clinical differences between men and women with PD.

Design/Methods DESIGN/METHODS: We performed a cross-sectional study of 170 subjects with Parkinson disease (40 women, 130 men) to explore gender differences in dopaminergic and cholinergic projection system integrity. Dopaminergic denervation was confirmed in all subjects by [11C]dihydrotetrabenazine (DTBZ) positron emission tomography (PET). All subjects underwent a clinical evaluation as well as cholinergic PET imaging with the [11C]PMP acetylcholinesterase (AChE) ligand. A smaller subset of subjects (n = 106; 30 women, 76 men) also underwent neuropsychological testing. Multivariable linear regression was used to compare the two genders.

Results RESULTS: After controlling for age, duration of motor disease, and education, men showed greater degrees of cholinergic denervation in neocortical (-6.8%, t=3.4, p =0.0008) and thalamic (-4.1%, t=2.06, p =0.041) regions of interest. Greater dopaminergic denervation was also seen amongst men in the caudate nucleus (-6.7%, t=3.16, p=0.002) but not the putamen (t=0.79, p =0.43). Subset analysis showed that men also scored lower on global cognitive Z-score (t=2.45, p =0.016) after controlling for age, education and duration of disease.

Conclusions CONCLUSIONS: Men with PD may exhibit more aggressive cholinergic denervation and dopaminergic denervation in the caudate nucleus. Absence of gender differences in putaminal dopaminergic activity may relate to a denervation 'floor' effect. Gender variations in projection system integrity may contribute towards cognitive differences between men and women with PD. Further research is needed to investigate whether relative preservation of dopaminergic and cholinergic innervation in women is related to possible neuroprotective effects of estrogens.

Authors/Disclosures
Vikas Kotagal, MD, FAAN (University of Michigan) PRESENTER	Dr. Kotagal has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Movement Disorders Society. The institution of Dr. Kotagal has received research support from NIH. The institution of Dr. Kotagal has received research support from VA Healthcare System.
Amanda S. Lindy, PhD (GeneDx, Inc.)	Dr. Lindy has received personal compensation for serving as an employee of GeneDx.
Roger L. Albin, MD (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.
Martijn Muller, PhD (Critical Path Institute)	No disclosure on file
	No disclosure on file
Sid Gilman, MD, FAAN	Dr. Gilman has nothing to disclose.
Kirk A. Frey, MD, PhD (Univ of Michigan/Univ Hosp BIG 412 0028)	No disclosure on file
Nicolaas I. Bohnen, MD, PhD, FAAN (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.
	No disclosure on file

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