Retrospective real-world pilot data on transcranial pulse stimulation in mild to severe Alzheimer's patients
Celine Cont, Nathalie Stute, Anastasia Galli, Christina Schulte, Kazimierz Logmin, Carlos Trenado, Lars Wojtecki, Celine Cont, Nathalie Stute, Anastasia Galli, Christina Schulte, Kazimierz Logmin, Carlos Trenado, Lars Wojtecki
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
References
- Breijyeh Z, Karaman R. Comprehensive review on alzheimer's disease: causes and treatment. Molecules. (2020) 25:5789. 10.3390/molecules25245789
- Mullard A. Landmark Alzheimer's drug approval confounds research community. Nature. (2021) 594:309–10. 10.1038/d41586-021-01546-2
- Sabbagh M, Sadowsky C, Tousi B, Agronin ME, Alva G, Armon C, et al. . Effects of a combined transcranial magnetic stimulation (TMS) and cognitive training intervention in patients with Alzheimer's disease. Alzheimers Dement. (2020) 16:641–50. 10.1016/j.jalz.2019.08.197
- Menardi A, Rossi S, Koch G, Hampel H, Vergallo A, Nitsche MA, et al. . Toward noninvasive brain stimulation 2.0 in Alzheimer's disease. Ageing Res Rev. (2022) 75:101555. 10.1016/j.arr.2021.101555
- Di Lazzaro V, Bella R, Benussi A, Bologna M, Borroni B, Capone F, et al. . Diagnostic contribution and therapeutic perspectives of transcranial magnetic stimulation in dementia. Clin Neurophysiol. (2021) 132:2568–607. 10.1016/j.clinph.2021.05.035
- Sanches C, Stengel C, Godard J, Mertz J, Teichmann M, Migliaccio R, Valero-Cabré A. Past, present, and future of non-invasive brain stimulation approaches to treat cognitive impairment in neurodegenerative diseases: time for a comprehensive critical review. Front Aging Neurosci. (2020) 12:578339. 10.3389/fnagi.2020.578339
- Beisteiner R, Matt E, Fan C, Baldysiak H, Schönfeld M, Philippi Novak T et al. Transcranial pulse stimulation with ultrasound in Alzheimer's disease—a new navigated focal brain therapy. Adv Sci. (2020) 7:1902583. 10.1002/advs.201902583
- Wang N, Tytell JD, Ingber DE. Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus. Nat Rev Mol Cell Biol. (2009) 10:75–82. 10.1038/nrm2594
- Matt E, Kaindl L, Tenk S, Egger A, Kolarova T, Karahasanović N, et al. . First evidence of long-term effects of transcranial pulse stimulation (TPS) on the human brain. J Transl Med. (2022) 20:26. 10.1186/s12967-021-03222-5
- Matt E, Dörl G, Beisteiner R. Transcranial pulse stimulation (TPS) improves depression in AD patients on state-of-the-art treatment. Alzheimers Dement. (2022) 8:e12245. 10.1002/trc2.12245
- Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. . NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement. (2018) 14:535–62. 10.1016/j.jalz.2018.02.018
- Kueper JK, Speechley M, Montero-Odasso M. The Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog): modifications and responsiveness in pre- dementia populations. A narrative review. J Alzheimers Dis. (2018) 63:423–44. 10.3233/JAD-170991
- Trzepacz PT, Hochstetler H, Wang S, Walker B, Saykin AJ. Relationship between the montreal cognitive assessment and mini-mental state examination for assessment of mild cognitive impairment in older adults. BMC Geriatr. (2015) 15:107. 10.1186/s12877-015-0103-3
- Tombaugh TN, McIntyre NJ. The mini-mental state examination: a comprehensive review. J Am Geriatr Soc. (1992) 40:922–35. 10.1111/j.1532-5415.1992.tb01992.x
- Cantone M, Lanza G, Ranieri F, Opie GM, Terranova C. Editorial: non- invasive brain stimulation in the study and modulation of metaplasticity in neurological disorders. Front Neurol. (2021) 12:721906. 10.3389/fneur.2021.721906
Source: PubMed