Retrospective real-world pilot data on transcranial pulse stimulation in mild to severe Alzheimer's patients

Abstract

Introduction: Transcranial pulse stimulation (TPS) is a non-invasive neuromodulation therapy that uses short, repetitive shockwaves through a neuro-navigated device. Current research suggests that these pulses lead to a wide range of vascular, metabolic, and neurotrophic changes. This relatively new CE-marked treatment provided first promising results in a clinical pilot study for improving cognition in mild-to-moderate Alzheimer's. Data from other centers is lacking, so here we analyzed safety and pilot real-world short-term results of TPS from the first center in Germany. To gain information about effects in different stages, patients with not only mild but also moderate-to-severe Alzheimer's were analyzed.

Methods: A total of 11 patients were retrospectively examined for cognitive and emotional function before and after the first stimulation series. The effect was assessed using several neuropsychological tests [Alzheimer's Disease Assessment Scale (ADAS), including the ADAS cognitive score (ADAS Cog) and ADAS affective scores, Mini-Mental Status Examination (MMSE), and Montreal Cognitive Assessment (MoCA)] including in comparison between the groups of mild-to-severe patients. Moreover, subjective improvement of symptom severity, potential effects on depressive symptoms, and side effects were analyzed using Numeric Rating Scales (NRS).

Results: Side effects were rare (in 4% of sessions) with moderate subjective severity and only transient. Patients significantly improved in the ADAS and ADAS Cog, while there was no significant effect in MMSE and MoCA. Patients' self-reported symptom severity improved significantly. The depressive symptoms measured in an ADAS subscale also improved significantly. Statistical data analyses revealed no significant correlation of clinical improvement with baseline symptom severity.

Conclusion: TPS might be a safe and promising add-on therapy for Alzheimer's, even for moderate-to-severe patients. More research on long-term effects in patients as well as studies with sham control groups is needed. Moreover, translational research on the mechanisms of action and effects on cerebral network physiology will be needed to understand this new neuromodulation technique.

Keywords: Alzheimer's disease (AD); dementia; neuromodulation; real-world data; transcranial pulse stimulation.

Conflict of interest statement

Author CC received travel fees from Storz Medical. LW has previously received funding grants and institutional support from the German Research Foundation, Hilde-Ulrichs-Stiftung für Parkinsonforschung, and the ParkinsonFonds Germany, BMBF/ERA-NETNEURON, DFG Forschergruppe (FOR1328), Deutsche Parkinson Vereinigung (DPV), Forschungskommission, Medizinische Fakultät, HHU Düsseldorf, UCB; Medtronic, UCB, Teva, Allergan, Merz, Abbvie, Roche, Bial, Merck, Novartis, Desitin, Spectrum. LW owned stock in company BioNTech SE. He is consultant to the following companies or received travel honarium from: TEVA, UCB Schwarz, Desitin, Medtronic, Abbott/Abbvie, MEDA, Boehringer I, Storz Medical, Kyowa Kirin, Guidepoint, Merck, Merz, Synergia, BIAL, Zambon, Sapio Life, STADA, Inomed, Vertanical. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Cont, Stute, Galli, Schulte, Logmin, Trenado and Wojtecki.

Figures

Figure 1

TPS system. 3D camera, navigation tracker and headpiece, and TPS handpiece with naviagation tracker. Image Source: Storz Medical.

Figure 2

(A) Example of axial T1 image with navigated visualization of applied pulse energy. Color code shows quantity of pulses and energy applied in predefined ROIs (turquoise ellipses) frontal, parietal, and precuneus with green indicating low, yellow indicating medium, and blue indicating high energy applied. Image source: Storz Medical. (B) Coronar T1 image of patient 10. Besides predefined ROI, pulses were also applied to the temporal cortex perinsular. (C) The parietal treatment ROI on coronar T1 from patient 2. (D) The treatment of precuneus with 600 pulses visualized on ROI on sagittal T1 image of patient 3. Please note that 3D ROIs are partly superimposed from other 2D plane sections.

Figure 3

Mean of the patient group's score of the Alzheimer's Disease Assessment Scale (ADAS) before the first stimulation (dark blue) and after the last stimulation (light blue). A lower score indicates a better performance. Box plot show destribution of the patients' data. (A) ADAS total score. The line represents the median of the group (baseline = 24.5, post-stimulation = 22.5), and the cross represents the mean scores [M baseline = 30.2 (SD 11.55), M post-stimulation = 25.8 (SD 10.71), *p = 0.01]. (B) ADAS cog score. The line represents the median of the group (baseline =22.5, post-stimulation = 21), and the cross represents the mean scores [M baseline = 25.8 (SD 10.77), M post-stimulation = 23.3 (SD 10.27), *p = 0.04].

Figure 4

Individual test results of the patients in Alzheimer's Disease Assessment Scale (ADAS) before the first stimulation (baseline) and after the last stimulation (post-stimulation). A lower score indicates a better performance. Each line represents one patient. (A) Individual scores of each patient in the ADAS total score. Best improvement was 15 points (ID 3). (B) Individual scores of each patient in the sub scale ADAS cog score. Best improvement was 14 points (ID 3 and ID 4).