History of falls in Parkinson disease is associated with reduced cholinergic activity.
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 [(11)C]methyl-4-piperidinyl propionate (PMP) acetylcholinesterase (AChE) and [(11)C]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.
Bohnen
N I
NI
Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor 48105-9755, USA. nbohnen@umich.edu
Müller
M L T M
ML
Koeppe
R A
RA
Studenski
S A
SA
Kilbourn
M A
MA
Frey
K A
KA
Albin
R L
RL
D000058:Accidental Falls; D000110:Acetylcholinesterase / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000503:physiopathology; D003430:Cross-Sectional Studies; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000503:physiopathology*; D049268:Positron-Emission Tomography; D013378:Substantia Nigra / Q000000981:diagnostic imaging / Q000503:physiopathology; D013788:Thalamus / Q000000981:diagnostic imaging / Q000503:physiopathology; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism*
C493452:SLC18A2 protein, human; D050493:Vesicular Monoamine Transport Proteins; D000110:Acetylcholinesterase; D004298:Dopamine