Independent review evaluates study results on TPS

Transcranial Pulse Stimulation (TPS): Potential for treating Alzheimer’s disease confirmed

With more than 55 million people affected by Alzheimer’s dementia worldwide (WHO, 2021) and increasing prevalence rates, Alzheimer’s disease has become an extremely burdensome and costly disease. Due to limited effectiveness and significant side effects of existing drug therapies, additional treatment options are being sought.

Researchers at Sichuan University in Chengdu, China, conducted a review of Transcranial Pulse Stimulation (TPS) to evaluate its utility. The findings were published July 20, 2023, in CNS Neuroscience & Therapeutics.

The independent research group from Sichuan University, renowned for medical quality control in China, analyzed the data on TPS neutrally and comprehensively. They followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline.

New techniques for brain stimulation: TPS compared with other procedures

The review authors note that noninvasive brain stimulation (NIBS) techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) may show beneficial effects on cognitive performance in AD. However, these techniques rely on electromagnetic effects that affect not only the site of stimulation but also other brain regions and cannot effectively reach the deeper neural tissues.

In contrast, according to the author:s, Transcranial Pulse Stimulation (TPS) can be targeted with a neuronavigation system because it does not rely on the electrical conductivity of the brain.

Aim of review: To evaluate the effect and safety of TPS in Alzheimer’s dementia

Also according to the analyses the Chinese researchers, Transcranial Pulse Stimulation (TPS) is a promising noninvasive brain stimulation procedure that can increase cortical and corticospinal excitability, induce neuroplasticity, and improve functional connectivity in the brain. Several studies had previously confirmed the potential of TPS in the treatment of Alzheimer’s disease (AD).

For analysis and assessment, study selection, data extraction, and study quality assessment were performed by two reviewers working independently. The Methodological Index for Nonrandomized Studies was used to assess potential risk of bias.

TPS significantly improves cognitive performance and depressive symptoms in validatable tests

Five studies involving a total of 99 patient:s with Alzheimer’s dementia were included in the review from 199 eligible articles. As a result, Transcranial Pulse Stimulation (TPS) significantly improved subjects’ cognitive performance on the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) test battery, the Alzheimer’s Disease Assessment Scale (cognitive), the Montreal Cognitive Assessment, and the Mini-Mental Status Examination.

Compared with baseline, TPS significantly increased ADAS total score and ADAS cognitive score in patients with AD. Overall, there was a 15.76 percent improvement in ADAS total score and an 8.65 percent improvement in ADAS cognitive score.

TPS also significantly reduced depressive symptoms as measured by the Alzheimer’s Disease Assessment Scale, the Geriatric Depression Score and the Beck Depression Inventory. The TPS technique improved cognitive performance in Alzheimer’s patient:s by increasing neuronal connectivity in specific brain regions while alleviating depressive symptoms. Adverse events such as headache, worsening mood, jaw pain, nausea, and drowsiness were rare, transient, and did not last longer than one day. No serious adverse events or complications were reported.

The safety of TPS in the treatment of Parkinson’s disease was also studied, and no adverse events were observed.

TPS may reduce cortical atrophy in Alzheimer’s dementia and modulate deep targets in the cortex

The studies reviewed indicated a significant correlation between improvement in neuropsychological CTS scores (before and after TPS) and increases in cortical thickness in specific brain regions. These regions are impaired early in the course of AD. TPS may therefore help to reduce cortical atrophy in AD.

According to the authors, the analyses of the present studies revealed that TPS can alter the electrical activity of cortical and subcortical structures. Due to the high spatial resolution of deep focal lengths, TPS can noninvasively modulate neuronal targets deep within the human cortex, reaching deep brain structures such as the thalamus. Compared with transcranial focused ultrasound stimulation (tFUS), TPS has the advantage of avoiding tissue heating and standing wave phenomena because very short pulses are applied.

Mechanisms of action of TPS in the Human Brain: High range of possible interactions

The various mechanisms of action of Transcranial Pulse Stimulation (TPS) have been intensively studied and discussed for many years. The potential mechanisms were summarized by Sichuan University researchers as follows:

The author:s state that changes in cell permeability have been observed, leading to a range of changes in transmitters, humoral factors, and cell activity. Transcranial Pulse Stimulation (TPS) reduces neuroinflammation by inhibiting the harmful overactivation of microglia. In addition, it directly affects cytoskeletal micro-tubules in neurons and glial cells.

The biological mechanism of TPS is that cells convert mechanical stimuli into biochemical reactions, triggering some basic cellular functions. TPS can stimulate mechanosensitive ion channels, promote cell proliferation and differentiation, stimulate brain-derived neurotrophic factor (BDNF) and vascular growth factors (VEGF), improve cerebral blood flow, promote angiogenesis, and induce neuroplasticity. It was also shown that TPS with shorter stimulation intervals appeared to have a greater effect on corticospinal excitability (CSE) with fewer side effects than tDCS with longer stimulation intervals.

TPS was shown to increase the power and connectivity of endogenous brain oscillations in a frequency-specific manner and to interact with endogenous oscillatory activity to induce cortical excitability. TPS mainly increased the interhemispheric coherence of brain oscillatory activity in the frontotemporal region, improving functional connectivity between neuronal networks.

TPS increased BDNF expression and enhanced neuroplasticity, possibly improving depressive symptoms in AD. However, the exact mechanism of action of TPS in AD has not been conclusively explored and requires further investigation.

Summary and Conclusions: TPS safe and effective adjunctive treatment of AD

As a result of their detailed and neutral review, the Chinese researcher:s evaluate Transcranial Pulse Stimulation (TPS) as a safe and effective adjunctive procedure for improving cognitive performance and reducing depressive symptoms in patient:s with Alzheimer’s dementia.

To their knowledge, this systematic review is the first to comprehensively evaluate the treatment and safety of TPS in AD. The studies in this review demonstrated that TPS significantly improved CERAD test battery, ADAS-cognitive, MoCA, and MMSE scores and significantly reduced ADAS-affective, GDS, and BDI scores in patient:s with AD.

In summary, the authors formulate that despite the still lack of high-quality randomized controlled trials, TPS has shown promise for improving cognitive performance and reducing depressive symptoms in patients with AD. Given the limited efficacy and side effects of existing AD drug therapies, TPS may have high potential as an adjunctive therapy for the treatment of AD. They recommend further study and investigation to further explore the potential of Transcranial Pulse Stimulation (TPS).