Gait speed in Parkinson disease correlates with cholinergic degeneration.
OBJECTIVE
We investigated dopaminergic and cholinergic correlates of gait speed in Parkinson disease (PD) and non-PD control subjects to test the hypothesis that gait dysfunction in PD may result from multisystem degeneration.


METHODS
This was a cross-sectional study. Subjects with PD but without dementia (n = 125, age 65.6 ± 7.3 years) and elderly subjects without PD (n = 32, age 66.0 ± 10.6 years) underwent [¹¹C]dihydrotetrabenazine dopaminergic and [(11)C]methyl-4-piperidinyl propionate acetylcholinesterase PET imaging, and cognitive and clinical testing, including an 8.5-m walk in the dopaminergic "off" state. The fifth percentile of cortical cholinergic activity in the elderly without PD was used to define normal-range activity in the subjects with PD.


RESULTS
Normal-range cortical cholinergic activity was present in 87 subjects with PD (69.6%). Analysis of covariance using gait speed as the dependent variable demonstrated a significant model (F = 6.70, p < 0.0001) with a significant group effect (F = 3.36, p = 0.037) and significant slower gait speed in the low cholinergic PD subgroup (0.97 ± 0.22 m/s) with no significant difference between the normal-range cholinergic PD subgroup (1.12 ± 0.20 m/s) and control subjects (1.17 ± 0.18 m/s). Covariate effects were significant for cognition (F = 6.58, p = 0.011), but not for striatal dopaminergic innervation, sex, or age.


CONCLUSIONS
Comorbid cortical cholinergic denervation is a more robust marker of slowing of gait in PD than nigrostriatal denervation alone. Gait speed is not significantly slower than normal in subjects with PD with relatively isolated nigrostriatal denervation.
From the Department of Radiology, Division of Nuclear Medicine (N.I.B., K.A.F., R.A.K., P.J.H.S., M.L.T.M.M.), and Department of Neurology (N.I.B., K.A.F., V.K., R.L.A.), University of Michigan; Neurology Service and GRECC (N.I.B., R.L.A.), VAAAHS, Ann Arbor, MI; and Department of Internal Medicine (S.S.), Division of Geriatrics, University of Pittsburgh, PA.
Nicolaas I
NI
Bohnen
Kirk A
KA
Frey
Stephanie
S
Studenski
Vikas
V
Kotagal
Robert A
RA
Koeppe
Peter J H
PJ
Scott
Roger L
RL
Albin
Martijn L T M
ML
Müller
D000110:Acetylcholinesterase / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002247:Carbon Isotopes; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology; D003430:Cross-Sectional Studies; D004148:Dioxolanes; D005260:Female; D020233:Gait Disorders, Neurologic / Q000000981:diagnostic imaging / Q000209:etiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000150:complications* / Q000201:enzymology*; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology*; D049268:Positron-Emission Tomography; D013747:Tetrabenazine / Q000031:analogs & derivatives; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism
D002247:Carbon Isotopes; D004148:Dioxolanes; C493452:SLC18A2 protein, human; D050493:Vesicular Monoamine Transport Proteins; C002888:methyl piperonylate; C032811:dihydrotetrabenazine; D000110:Acetylcholinesterase; D013747:Tetrabenazine