Gait speed in Parkinson disease correlates with cholinergic degeneration. Neurology

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 (Impact Factor: 8.29). 09/2013; 81(18). DOI: 10.1212/WNL.0b013e3182a9f558
Source: PubMed


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.
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 [(11)C]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.
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.
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.

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Available from: Nico Bohnen, Sep 13, 2015
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    • "If these cortices were to lack cholinergic input such compensatory recruitment would remain largely ineffective. The recent finding that slow gait speed in PD patients is correlated with comorbid cholinergic cell loss, but is not affected in patients with relatively isolated dopamine loss (Bohnen et al., 2013) is also consistent with the hypothesis that cholinergic cell loss unmasks the low-vigor gait resulting from striatal dopamine loss (Mazzoni et al., 2007; Niv et al., 2007). Partial striatal dopamine loss alone did not result in impairments in MCMCT performance, suggesting that compensatory attentional mechanisms contributed to the prevention of falls in these animals. "
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