Gait Speed Is Preserved in Oligosystem Compared to Multisystem Neurodegeneration in Parkinson Disease (P04.165)

OBJECTIVE: To investigate neural correlates of walking speed in Parkinson disease (PD). 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: 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: 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: 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. Supported by: NIH grants PO1 NS015655, RO1 NS070856, Department of Veterans Affairs and the Michael J. Fox Foundation. Disclosure: Dr. Bohnen has nothing to disclose. Dr. Kotagal has received research support from National Institutes of Health T32 training grant (NS007222) and the American Academy of Neurology Clinical Research Training Fellowship. Dr. Albin has received personal compensation for activities with Garan, Lucow, Miller PC as expert witness consulting in medical malpractice litigation. Dr. Albin has received research support from CHDI Foundation and National Institutes of Health. Dr. Koeppe has nothing to disclose. Dr. Frey has received personal compensation for activities with Bayer-Schering Pharmaceuticals, Avid Radiopharmaceuticals, MIMVista, Inc, and GE Healthcare as a consultant. Dr. Frey holds stock and/or stock options in General Electric, Bristol-Myers Squibb, Merck, and Novo Nordisk. Dr. Muller has nothing to disclose.