Postural instability and freezing of gait are the most debilitating
dopamine-refractory motor impairments in advanced stages of
Parkinson's disease because of increased risk of falls and poorer quality of life. Recent findings suggest an inability to efficaciously utilize vestibular information during static posturography among people with
Parkinson's disease who exhibit freezing of gait, with associated changes in
cholinergic system integrity as assessed by
vesicular acetylcholine transporter PET. There is a lack of adequate understanding of how postural control varies as a function of available sensory information in patients with
Parkinson's disease with freezing of gait. The goal of this cross-sectional study was to examine cerebral
cholinergic system changes that associate with inter-sensory postural control processing features as assessed by dynamic computerized posturography and
acetylcholinesterase PET. Seventy-five participants with
Parkinson's disease, 16 of whom exhibited freezing of gait, underwent computerized posturography on the NeuroCom© Equitest sensory organization test platform, striatal
dopamine, and
acetylcholinesterase PET scanning. Findings demonstrated that patients with
Parkinson's disease with freezing of gait have greater difficulty maintaining balance in the absence of reliable proprioceptive cues as compared to those without freezing of gait [β = 0.28 (0.021, 0.54), P = 0.034], an effect that was independent of disease severity [β = 0.16 (0.062, 0.26), P < 0.01] and age [β = 0.092 (-0.005, 0.19), P = 0.062]. Exploratory voxel-based analysis revealed an association between postural control and right hemispheric
cholinergic network related to visual-vestibular integration and self-motion perception. High
anti-cholinergic burden predicted postural control impairment in a manner dependent on right hemispheric cortical
cholinergic integrity [β = 0.34 (0.065, 0.61), P < 0.01]. Our findings advance the perspective that cortical
cholinergic system might play a role in supporting postural control after nigro-striatal dopaminergic losses in
Parkinson's disease. Failure of cortex-dependent visual-vestibular integration may impair detection of postural instability in absence of reliable proprioceptive cues. Better understanding of how the
cholinergic system plays a role in this process may augur novel treatments and therapeutic interventions to ameliorate debilitating symptoms in patients with advanced
Parkinson's disease.