Abstract
241476
Introduction: The cholinergic system has been implicated in postural deficits, in particular falls, in Parkinson’s disease (PD). Falls and freezing of gait typically occur during dynamic and challenged balance and gait conditions, such as when initiating gait, experiencing postural perturbations, or making turns. However, the precise cholinergic neural substrate underlying dynamic postural and gait changes remain poorly understood. This study aimed to examine regional cerebral vesicular acetylcholine transporter ligand [18F]-Fluoroethoxybenzovesamico (FEOBV) binding correlates of dynamic gait and balance impairments in people with PD (PwPD).
Methods: This cross-sectional study involved 125 patients with PD (M97/F28); mean age 66.89±7.71 years, mean motor disease duration 6.12±4.77 years. All the patients underwent dynamic gait and balance evaluation using the abbreviated Balance Evaluation Systems Test (Mini-Best test) total and its four functional domain sub-scores (anticipatory postural control, reactive postural control, dynamic gait and sensory integration) (Figure 1). All participants also underwent [18F]-FEOBV brain PET scan. [18F]-FEOBV PET images were analyzed non-invasively using a supratentorial white matter reference tissue approach. Whole-brain voxel-based [18F]-FEOBV PET and Mini-BESTest total score and sub-scores correlational analyses were performed using parametric SPM12 or non-parametric (SnPM) software after adjustment for levodopa equivalent dose dependent on the data distribution. Significance thresholds after FDR correction were set at P < 0.05. Trending correlations which fail to survive FDR correction are presented at an uncorrected threshold of P < 0.001 (Figure 2).
Results: Whole brain false discovery-corrected ( P < 0.05) correlations for total abbreviated Balance Evaluation Systems Test scores included the following bilateral or asymmetric hemispheric regions: gyrus rectus, orbitofrontal cortex, anterior part of the dorsomedial prefrontal cortex, dorsolateral prefrontal cortex, cingulum, frontotemporal opercula, insula, fimbria, right temporal pole, mesiotemporal, parietal and visual cortices, caudate nucleus, lateral and medial geniculate bodies, thalamus, lingual gyrus, cerebellar hemisphere lobule VI, left cerebellar crus I, superior cerebellar peduncles, flocculus, and nodulus. No significant correlations were found for the putamen or anteroventral putamen. The four domain-specific sub-scores demonstrated overlapping cholinergic topography in the metathalamus, fimbria, thalamus proper, and prefrontal cortices but also showed distinct topographic variations. For example, reactive postural control functions involved the right flocculus but not the upper brainstem regions. The anterior cingulum was associated with reactive postural control, whereas the posterior cingulum correlated with anticipatory control. The spatial extent of associated cholinergic system changes was the least for dynamic gait and sensory orientation functional domains compared to the anticipatory and reactive postural control functions.
Conclusions: We conclude that specific aspects of dynamic balance and gait deficits in Parkinson’s disease are associated with overlapping but also distinct patterns of cerebral cholinergic system changes in numerous brain regions. Our study also presents novel evidence of cholinergic topography involved in dynamic balance and gait in Parkinson’s disease that have not been typically associated with mobility disturbances, such as the right anterior temporal pole, right anterior part of the dorsomedial prefrontal cortex, gyrus rectus, fimbria, lingual gyrus, flocculus, modulus and right cerebellar hemisphere lobules VI and left crus I.
This study was funded by the National Institutes of Health (R01 AG073100, P01 NS015655, RO1 NS070856, P50 NS091856, P50 NS123067), Department of Veterans Affairs grant (I01 RX001631), the Michael J. Fox Foundation, and the Parkinson’s Foundation.
In this issue
Jump to section
Related Articles
Cited By...
- No citing articles found.