Mesocorticolimbic dopaminergic innervation modulates Levodopa-related improvements in gait in older slow walking Adults: A [11C]PE2I PET study

Purpose

Slow walking in healthy older adults may result from multifactorial deficits involving the muscular, peripheral, and central nervous systems. While mobility depends on these systems, the brain’s neuromodulatory capacity may offer insights for interventions. This open-label imaging study tested whether the dopaminergic system serves as a resilience mechanism for gait in the elderly. Using [¹¹C]PE2I dopamine transporter (DAT) PET, we assessed whether baseline dopaminergic innervation modulates the response to a one-week carbidopa-levodopa regimen in slow-walking older adults without Parkinson’s disease (PD).

Methods

Slow walking older adults without clinical evidence of PD (n = 9) were pre-treated with carbidopa 25 mg one tablet TID for three days, followed by carbidopa-levodopa 25/100 mg starting at one tablet TID for three days and then increased to 1.5 tablets of carbidopa-levodopa 25/100 mg TID daily for four days, as tolerated. [¹¹C]PE2I DAT PET imaging was completed at baseline. Spatiotemporal gait parameters were evaluated at pre-intervention, following carbidopa pre-treatment, and post-intervention.

Results

Levodopa treatment resulted in improved gait speed (β = 0.69 [0.07, 1.30], p = 0.031), double-support time (β = -0.26 [-0.51, −0.01], p = 0.041), and cadence (β = 0.54 [0.18, 0.89], p = 0.005), but not in turn duration (β = 0.41 [-0.33, 1.14], p = 0.264). These changes were strongly predicted by pre-treatment limbic, subcortical, and neocortical DAT PET uptake, with greater improvements in gait pace observed among individuals with lower DAT availability.

Conclusion

These preliminary findings suggest that the mesocorticolimbic dopaminergic system may be the substrate of a resilience mechanism that can be targeted to manage gait impairments in older adults.