Abstract Details

Title Gait Speed Is Preserved in Oligosystem Compared to Multisystem Neurodegeneration in Parkinson Disease

Topic Movement Disorders

Presentation(s) P04 - (-)

Poster/Presentation
Number 165

Objective

Background BACKGROUND: PD is a multisystem neurodegeneration and differences in the degree of degeneration of different CNS systems may account for differences in phenotypic features. While there is uniform and severe dopaminergic denervation in early PD, neocortical cholinergic denervation is more heterogeneous and marked cholinergic denervation present in only about one third of non-demented PD subjects.

Design/Methods DESIGN/METHODS: PD subjects without dementia (n=119, F31/M88, age 65.1±7.4, HY stage 2.4±0.5) and 32 control subjects (F14/M18, mean age 66.0±10.6) underwent [C-11]PMP acetylcholinesterase (AChE) and [C-11]DTBZ dopaminergic PET imaging, and clinical assessment, including a timed 8.5 meter walk in the dopaminergic "off" state. The 5th percentile of neocortical AChE activity in the non-PD elderly was used to define below normal range activity levels.

Results RESULTS: Cholinergic denervation was heterogeneous with 34 PD subjects (28.6%) exhibiting neocortical AChE activity below normal range. ANCOVA comparing walking time between the three groups showed a significant overall model (F=5.40, P=0.0004) with a significant neocortical AChE effect (F=4.71, P=0.01) and significant slower walking time in the low cholinergic PD sub-group (n=34, 9.34±2.75) compared to the normal range cholinergic PD sub-group (n=95, 7.92±1.72) and non-PD control subjects (n=32, 7.46±1.30s). There were no significant striatal dopaminergic (F=1.03, P=0.31) or duration of disease (F=1.85, P=0.17) covariate effects. There was no significant difference in walking times between normal cholinergic range PD and non-PD control groups. Walking time was inversely related to global cognition in the PD subjects (R=-0.28, P=0.0007).

Conclusions CONCLUSIONS: Comorbid neocortical cholinergic denervation is a more robust marker of slowing of gait in PD than nigrostriatal denervation alone and may reflect failing cognitive processing abilities during ambulation. Gait speed is not significantly slower than normal in subjects with PD with relatively isolated nigrostriatal dopaminergic denervation.

Authors/Disclosures
Nicolaas I. Bohnen, MD, PhD, FAAN (University of Michigan) PRESENTER	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.
Vikas Kotagal, MD, FAAN (University of Michigan)	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.
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.
	No disclosure on file
Kirk A. Frey, MD, PhD (Univ of Michigan/Univ Hosp BIG 412 0028)	No disclosure on file
Burk Jubelt, MD (SUNY Upstate Medical University)	No disclosure on file
Martijn Muller, PhD (Critical Path Institute)	No disclosure on file

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