Objective: To investigate the relationship between regional cerebral expression of benzodiazepine receptors and gait speed in Parkinson’s disease (PD).

Background: Flumazenil is a short-acting intravenously administered gamma-aminobutyric acid (GABA-A) antagonist which has shown to rapidly improve motor impairments in PD. Based upon current basal ganglion models in PD, flumazenil could normalize neuronal signaling at several different locations but little is known about the relationship between regional cerebral benzodiazepine receptor expression and gait speed in PD. We have previously shown that gait speed is a correlate of cortical cholinergic activity in PD.

Methods: PD patients [N=16 (15M); 67.9 ± 4.9 years old; 10.6 ± 4.4 years motor disease duration, HY range 2-3, mean MMSE score 28.5 ± 2.1 and mean UPDRS motor score of 29.1 ± 11.4] underwent [C¹¹]flumazenil GABA-A receptor and [C¹¹]PMP (acetylcholinesterase) brain PET scanning and clinical assessment. Gait speed was assessed as the time needed to walk a 8.5 meter pathway in the dopaminergic “off” state.

Results: Stepwise regression analysis was used to best predict regional cerebral correlates of gait speed using cortical, caudate nucleus, putamen, thalamic and cerebellar flumazenil binding estimates using a 0.15 significance model entry level. The overall model was significant (R²=0.35) with only cerebellar receptor activity as the single predictor in the model (F=7.57, P=0.016). Cerebellar receptor activity and gait speed correlation findings remained significant after adjustment for cortical cholinergic activity.

Conclusions: Cerebellar GABA-A receptor expression is inversely correlated with gait speed in PD independent from cortical cholinergic status. Findings may augur novel non-dopaminergic approaches to treating gait difficulties in PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cerebellar-gaba-a-receptor-activity-is-inversely-correlated-with-gait-speed-in-parkinsons-disease/