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26.06.2022 | Neurology and Preclinical Neurological Studies - Original Article

Cholinergic brain network deficits associated with vestibular sensory conflict deficits in Parkinson’s disease: correlation with postural and gait deficits

verfasst von: Nicolaas I. Bohnen, Prabesh Kanel, Stiven Roytman, Peter J. H. Scott, Robert A. Koeppe, Roger L. Albin, Kevin A. Kerber, Martijn L. T. M. Müller

Erschienen in: Journal of Neural Transmission | Ausgabe 8/2022

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Abstract

To examine regional cerebral vesicular acetylcholine transporter (VAChT) ligand [¹⁸F]fluoroethoxybenzovesamicol ([¹⁸F]-FEOBV) PET binding in Parkinson’ disease (PD) patients with and without vestibular sensory conflict deficits (VSCD). To examine associations between VSCD-associated cholinergic brain deficits and postural instability and gait difficulties (PIGD). PD persons (M70/F22; mean age 67.6 ± 7.4 years) completed clinical assessments for imbalance, falls, freezing of gait (FoG), modified Romberg sensory conflict testing, and underwent VAChT PET. Volumes of interest (VOI)-based analyses included detailed thalamic and cerebellar parcellations. VSCD-associated VAChT VOI selection used stepwise logistic regression analysis. Vesicular monoamine transporter type 2 (VMAT2) [¹¹C]dihydrotetrabenazine (DTBZ) PET imaging was available in 54 patients. Analyses of covariance were performed to compare VSCD-associated cholinergic deficits between patients with and without PIGD motor features while accounting for confounders. PET sampling passed acceptance criteria in 73 patients. This data-driven analysis identified cholinergic deficits in five brain VOIs associating with the presence of VSCD: medial geniculate nucleus (MGN) (P < 0.0001), para-hippocampal gyrus (P = 0.0043), inferior nucleus of the pulvinar (P = 0.047), fusiform gyrus (P = 0.035) and the amygdala (P = 0.019). Composite VSCD-associated [¹⁸F]FEOBV-binding deficits in these 5 regions were significantly lower in patients with imbalance (− 8.3%, F = 6.5, P = 0.015; total model: F = 5.1, P = 0.0008), falls (− 6.9%, F = 4.9, P = 0.03; total model F = 4.7, P = 0.0015), and FoG (− 14.2%, F = 9.0, P = 0.0043; total model F = 5.8, P = 0.0003), independent of age, duration of disease, gender and nigrostriatal dopaminergic losses. Post hoc analysis using MGN VAChT binding as the single cholinergic VOI demonstrated similar significant associations with imbalance, falls and FoG. VSCD-associated cholinergic network changes localize to distinct structures involved in multi-sensory, in particular vestibular, and multimodal cognitive and motor integration brain regions. Relative clinical effects of VSCD-associated cholinergic network deficits were largest for FoG followed by postural imbalance and falls. The MGN was the most significant region identified.

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Titel: Cholinergic brain network deficits associated with vestibular sensory conflict deficits in Parkinson’s disease: correlation with postural and gait deficits
verfasst von: Nicolaas I. Bohnen
Prabesh Kanel
Stiven Roytman
Peter J. H. Scott
Robert A. Koeppe
Roger L. Albin
Kevin A. Kerber
Martijn L. T. M. Müller
Publikationsdatum: 26.06.2022
Verlag: Springer Vienna
Erschienen in: Journal of Neural Transmission / Ausgabe 8/2022
Print ISSN: 0300-9564
Elektronische ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-022-02523-3

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