The pathophysiology of postural instability in
Parkinson's disease remains poorly understood. Normal postural function depends in part on the ability of the postural control system to integrate visual, proprioceptive, and vestibular sensory information. Degeneration of cholinergic neurons in the brainstem pedunculopontine nucleus complex and their thalamic efferent terminals has been implicated in postural control deficits in
Parkinson's disease. Our aim was to investigate the relationship of
cholinergic terminal loss in thalamus and cortex, and nigrostriatal dopaminergic
denervation, on postural sensory integration function in
Parkinson's disease. We studied 124 subjects with
Parkinson's disease (32 female/92 male; 65.5 ± 7.4 years old; 6.0 ± 4.2 years motor disease duration; modified Hoehn and Yahr mean stage 2.4 ± 0.5) and 25 control subjects (10 female/15 male, 66.8 ± 10.1 years old). All subjects underwent (11)C-dihydrotetrabenazine vesicular monoaminergic transporter type 2 and (11)C-methylpiperidin-4-yl
propionate acetylcholinesterase positron emission tomography and the sensory organization test balance platform protocol. Measures of dopaminergic and
cholinergic terminal integrity were obtained, i.e. striatal vesicular monoaminergic transporter type 2 binding (distribution volume ratio) and thalamic and cortical
acetylcholinesterase hydrolysis rate per minute (k3), respectively. Total centre of pressure excursion (speed), a measure of total sway, and sway variability were determined for individual sensory organization test conditions. Based on normative data, principal component analysis was performed to reduce postural sensory organization functions to robust factors for regression analysis with the dopaminergic and
cholinergic terminal data. Factor analysis demonstrated two factors with eigenvalues >2 that explained 52.2% of the variance, mainly reflecting postural sway during sensory organization test Conditions 1-3 and 5, respectively. Regression analysis of the Conditions 1-3 postural sway-related factor [R(2)adj = 0.123, F(5,109) = 4.2, P = 0.002] showed that decreased thalamic
cholinergic innervation was associated with increased centre of pressure sway speed (β = -0.389, t = -3.4, P = 0.001) while controlling for covariate effects of cognitive capacity and parkinsonian motor impairments. There was no significant effect of cortical
cholinergic terminal deficits or striatal dopaminergic terminal deficits. This effect could only be found for the subjects with
Parkinson's disease. We conclude that postural sensory integration function of subjects with
Parkinson's disease is modulated by pedunculopontine nucleus-thalamic but not cortical
cholinergic innervation. Impaired integrity of pedunculopontine nucleus cholinergic neurons and their thalamic efferents play a role in postural control in patients with
Parkinson's disease, possibly by participating in integration of multimodal sensory input information.