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Gait disturbance is a common and severe symptom of Parkinson's disease that severely impairs quality of life. Current treatments provide only partial benefits with wide variability in outcomes. Also, deep brain stimulation of the subthalamic nucleus (STN-DBS), a mainstay treatment for bradykinetic-rigid symptoms and parkinsonian tremor, is poorly effective on gait. We applied a novel DBS paradigm, adjusting the current amplitude linearly with respect to subthalamic beta power (adaptive DBS), in one parkinsonian patient with gait impairment and chronically stimulated with conventional DBS. We studied the kinematics of gait and gait initiation (anticipatory postural adjustments) as well as subthalamic beta oscillations with both conventional and adaptive DBS. With adaptive DBS, the patient showed a consistent and long-lasting improvement in walking while retaining benefits on other disease-related symptoms. We suggest that adaptive DBS can benefit gait in Parkinson's disease possibly by avoiding overstimulation and dysfunctional entrainment of the supraspinal locomotor network., Competing Interests: IUI is Newronika S.p.A. consultant. IUI is Adjunct Professor at the Department of Neurology, NYU Grossman School of Medicine. IUI and LB received research fundings (paid to the Institution) by Newronika S.p.A. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Isaias, Caffi, Borellini, Ampollini, Locatelli, Pezzoli, Mazzoni and Palmisano.)

Background/Objectives : High cognitive reserve (CR) has been shown to have beneficial effects on global cognition, cognitive decline, and risk of dementia in Parkinson's disease (PD). We evaluated the influence of CR on the long-term cognitive outcomes of patients with PD who underwent subthalamic nucleus deep brain stimulation (STN-DBS). Methods: Twenty-five patients with PD underwent neuropsychological screening using the Montreal Cognitive Assessment (MoCA) at baseline, 1 year, and 5 years after bilateral STN-DBS. CR was assessed using the Cognitive Reserve Index questionnaire. According to CR score, patients were assigned to two different groups (LowCR group ≤ 130, HighCR group > 130). Results: Our data showed that patients in the HighCR group obtained a better performance with the MoCA total score at long-term follow-up compared to those in the LowCR group ([mean ± SE] LowCR group: 21.4 ± 1.2 vs. HighCR group: 24.5 ± 1.3, p = 0.05). The cognitive profile of the HighCR group remained unchanged over time. Conversely, the LowCR group had worse global cognition 5 years after surgery (T0: 25.3 ± 0.6 vs. T2: 21.4 ± 1.2, p = 0.02). Cognitive decline was not associated with mood, demographics, or clinical variables. Conclusions: These preliminary findings suggest that higher CR may be protective in PD cognition after STN-DBS. Specifically, a high CR may help cope with long-term decline in the context of surgical treatment. Quantifying a patient's CR could lead to more personalized medical care, tailoring postoperative support and monitoring for those at higher risk of cognitive decline.

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.