Falls gait cholinergic pedunculopontine Bohnen it al 2009

[aspergerian]

History of falls in Parkinson disease is associated with reduced cholinergic activity.

N I. Bohnen, MD, PhD, M L.T.M. Müller, PhD, [...], and R L. Albin, MD.

ncbi.nlm.nih.gov/pmc/articl...

Falls are common and disabling in Parkinson disease (PD).1 Because of nigrostriatal pathology in PD, it is asserted often that postural instability is attributable mainly to striatal dopaminergic denervation. However, balance-related deficits are least responsive to levodopa treatment.1,2 Therefore, there is a need to explore nondopaminergic mechanisms of gait control in PD. Until recently, gait was generally viewed as a largely automated motor task, requiring minimal cognitive input. Increasing evidence, however, links alterations in cognitive function to gait disturbances.3 Cortical cholinergic denervation in PD is associated with cognitive impairment4 but effects of alterations in cholinergic neurotransmission on mobility control in PD are poorly understood. There are 2 major sources of cholinergic projections in the brain. The nucleus basalis of Meynert (NBM) provides the principal cholinergic input of the entire cortical mantle and degenerates in PD.5 The pedunculopontine nucleus (PPN), a brainstem locomotor center, provides cholinergic inputs to the basal ganglia, thalamus, cerebellum, several brainstem nuclei, and the spinal cord,6 and also degenerates in PD.7.

DISCUSSION.

Our findings indicate that unlike nigrostriatal dopaminergic denervation, thalamic cholinergic denervation is associated with falls in PD. Although PD fallers had significantly lower cortical and thalamic AChE activity compared to nonfallers and control subjects, thalamic AChE enzyme hydrolysis rates remained significantly decreased even after adjusting for the degree of nigrostriatal dopaminergic denervation. Thalamic AChE activity derives mainly from terminals of brainstem PPN neurons that play a central role in the generation of movement.7 The PPN is located in the dorsolateral part of the pontomesencephalic tegmentum,21 and is composed of 2 groups of neurons: a pars compacta predominantly containing cholinergic projection neurons and a pars dissipata containing glutamatergic projections. The PPN sends profuse ascending cholinergic efferent fibers to several thalamic nuclei, particularly the intralaminar complex that is also reciprocally connected with the basal ganglia.7 PPN efferents appear to be highly collateralized and loss of thalamic AChE is likely to reflect PPN neuron dysfunction or degeneration. Our results are consistent with a key role for the PPN in the maintenance of balance in humans and with PPN dysfunction/degeneration as a cause of impaired postural control and gait in PD.