NEUROLOGY 2009;73:1670-1676
© 2009 American Academy of Neurology
History of falls in Parkinson disease is associated with reduced cholinergic activity
N. I. Bohnen, MD, PhD,
M. L.T.M. Müller, PhD,
R. A. Koeppe, PhD,
S. A. Studenski, MD, MPH,
M. A. Kilbourn, PhD,
K. A. Frey, MD, PhD and
R. L. Albin, MD
From the Department of Radiology, Division of Nuclear Medicine (N.I.B., M.L.T.M.M., R.A.K., M.A.K., K.A.F.), and Department of Neurology (N.I.B., K.A.F., R.L.A.), University of Michigan, Ann Arbor; Neurology Service and GRECC (N.I.B., R.L.A.), VAAAHS, Ann Arbor, MI; and Geriatric Service and GRECC (S.A.S.), VAPHS, Pittsburgh, PA.
Address correspondence and reprint requests to Dr. Nicolaas I. Bohnen, Functional Neuroimaging, Cognitive and Mobility Laboratory, Departments of Radiology and Neurology, University of Michigan, 24 Frank Lloyd Wright Drive, Box 362, Ann Arbor, MI 48105-9755 nbohnen{at}umich.edu
Objective: To investigate the relationships between history of falls and cholinergic vs dopaminergic denervation in patients with Parkinson disease (PD).
Background: There is a need to explore nondopaminergic mechanisms of gait control as the majority of motor impairments associated with falls in PD are resistant to dopaminergic treatment. Alterations in cholinergic neurotransmission in PD may be implicated because of evidence that gait control depends on cholinergic system–mediated higher-level cortical and subcortical processing, including pedunculopontine nucleus (PPN) function.
Methods: In this cross-sectional study, 44 patients with PD (Hoehn & Yahr stages I–III) without dementia and 15 control subjects underwent a clinical assessment and [11C]methyl-4-piperidinyl propionate (PMP) acetylcholinesterase (AChE) and [11C]dihydrotetrabenazine (DTBZ) vesicular monoamine transporter type 2 (VMAT2) brain PET imaging.
Results: Seventeen patients (38.6%) reported a history of falls and 27 patients had no falls. Analysis of covariance of the cortical AChE hydrolysis rates demonstrated reduced cortical AChE in the PD fallers group (–12.3%) followed by the PD nonfallers (–6.6%) compared to control subjects (F = 7.22, p = 0.0004). Thalamic AChE activity was lower only in the PD fallers group (–11.8%; F = 4.36, p = 0.008). There was no significant difference in nigrostriatal dopaminergic activity between PD fallers and nonfallers.
Conclusions: Unlike nigrostriatal dopaminergic denervation, cholinergic hypofunction is associated with fall status in Parkinson disease (PD). Thalamic AChE activity in part represents cholinergic output of the pedunculopontine nucleus (PPN), a key node for gait control. Our results are consistent with other data indicating that PPN degeneration is a major factor leading to impaired postural control and gait dysfunction in PD.
Abbreviations: AChE = acetylcholinesterase; ANCOVA = analysis of covariance; MMSE = Mini-Mental State Examination; PD = Parkinson disease; PPN = pedunculopontine nucleus; PSP = progressive supranuclear palsy; UPDRS = Unified Parkinson’s Disease Rating Scale; VOI = volume of interest.
Disclosure: Author disclosures are provided at the end of the article.
Received March 25, 2009. Accepted in final form August 20, 2009.
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