Cholinergic patterns correlate with dopamine medication ON freezing of gait in Parkinson’s disease
Commentary by Prof. Nico Bohnen
A recent very interesting study from Denmark investigated cholinergic system changes using VAChT FEOBV PET combined with in‑home, waist‑worn tri‑axial accelerometer recordings to quantify FOG. Using this sensor‑based FOG severity measure of ON- and OFF-FOG, and principal component analysis of the PET data, the authors did not find any significant cholinergic associations with OFF-FOG. In contrast, ON-FOG correlated significantly with cholinergic reductions in the bilateral striatum (anteroventral striata, caudate nuclei, putamina), with more limited and scattered involvement of the thalamus, hippocampus, anterior cingulate, a small brainstem cluster consistent with the MLR region, and cerebellar vermis. These findings underscore the importance of diffuse striatal and subcortical cholinergic losses in ON-state FOG. Limitations included the absence of a formal gold‑standard validation of FOG detection and the lack of quantitative comparison between ON and OFF medication states to characterize levodopa‑refractory freezing more directly.
Cholinergic System Changes in Dopa-Unresponsive Freezing of Gait in Parkinson’s Disease
Commentary by Prof. Tuhin Virmani
Levodopa unresponsive Freezing of Gait (FOG) also termed OFFON-FOG, is a significantly debilitating motor feature of Parkinson’s disease (PD). In this study Chou and colleagues utilized historical videos of standardized gait evaluations in the levodopa medicated (ON) and unmedicated (OFF) states in 36 people with PD. Based on the number of freezing episodes scored in these two states, the authors classified levodopa responsive freezers as those who had a decrease in the number of freezing episodes in the ON-levodopa state compared to the OFF-levodopa state, while levodopa unresponsive freezers did not show a decrease. Based on this classification, levodopa unresponsive freezers (n=16) had more severe cholinergic terminal reductions using [18F]FEOBV PET in the bilateral insula, hippocampi, fimbria and posterior cingulate and also in the right mid-frontal regions and anterior ventral nucleus of the thalamus, compared to levodopa responsive freezers (n=20). While this classification of freezing subtypes is a little different than recently proposed by Tosserams et al., it still provides potential insight, suggesting that less responsive freezers had worse cholinergic dysfunction. Future prospective studies longitudinally assessing cholinergic dysfunction as people progress from primarily levodopa responsive to levodopa unresponsive freezing will help shed further light on this phenomenon that has been difficult to define pathophysiologically.
Photo by Hal Gatewood on Unsplash