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

Abstract

IntroductionTranscranial 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.MethodsA 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).ResultsSide 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.ConclusionTPS 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.

Transcranial pulse stimulation in Alzheimer's disease

“…Only the study by Cont et al 26 reported the ADAS total score, ADAS cognitive score, MMSE, and MoCA. Compared to baseline, TPS significantly increased the ADAS total score and ADAS cognitive score in patients with AD.…”

“…The ADAS is generally more sensitive than the MMSE and MoCA scales. 34 , 35 , 36 Cont et al 26 performed a subgroup analysis of patients with AD of varying severity and found that TPS improved more in the group with moderate and severe cognitive impairment than in the group with mild cognitive impairment across all cognitive assessments. This suggests the need to consider a ceiling effect of TPS on mildly affected patients with AD.…”

“…In 2019, the first pilot study 25 using TPS to treat AD found improvements in cognitive ability and depressive symptoms in patients, which lasted up to 3 months, and confirmed changes in memory network connectivity after TPS treatment by functional magnetic resonance imaging (fMRI). Subsequently, to verify and explore the efficacy, safety, and mechanism of TPS in the treatment of AD, several clinical trials have been completed and reported 26–29 . However, the research emphases of these studies were not entirely consistent, and the quality of the studies was different.…”

“…Subsequently, to verify and explore the efficacy, safety, and mechanism of TPS in the treatment of AD, several clinical trials have been completed and reported. 26 , 27 , 28 , 29 However, the research emphases of these studies were not entirely consistent, and the quality of the studies was different. To provide an unbiased summary and evaluate the quality of these studies, we conducted a systematic review, which can provide suggestions for further research on the treatment of AD by the new TPS technique.…”

The Prospect of Focal Ultrasound in the Treatment of Mental Disorders

“…The authors pointed out that treatment of different brain regions along with the effect of MRgFUS on AD needs to be properly characterized [31]. In addition, recent clinical AD studies based on transcranial pulsed stimulation (TPS), which consists of short (3 µs), repetitive ultrasound shockwaves, reported scarce side effects as well as improvement in the Alzheimer's disease Assessment Scale (ADAS) and the ADAS cognitive scores [32], and improvement of depression scores (BDI-II) accompanied by effects in functional connectivity after one session of TPS [33]. Furthermore, TPS enabled induction of neuroplasticity changes up to one week after the last stimulation within a three-week experimental longitudinal protocol [34].…”