Efficacy of a 24-week Long Term Transcranial Pulse Stimulation (TPS) on Cognition and Brain Structure in Older Adults With Mild Neurocognitive Disorder (NCD)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Change in Global Cognition
研究概览
简要总结
Background:
Dementia, now known as major neurocognitive disorder (NCD), is a great health burden in Hong Kong and worldwide. In principle, to achieve its optimal benefits, intervention for dementia should begin at the earliest preclinical stage, which is defined as mild cognitive impairment (MCI). However, no evidence has been found to support a pharmacological approach to the prevention or postponement of cognitive decline during the stage of mild NCD. Non-invasive brain stimulation (NIBS) is increasingly recognized as a potential alternative to tackle this problem.
The typical examples of NIBS are transcranial direct current stimulation (DCS) and transcranial magnetic stimulation (MS). Besides these, there is a new NIBS named transcranial pulse stimulation (TPS), which recently obtained CE marking in 2018 for the treatment of the central nervous system (CNS) in patients with mild to moderate Alzheimer's disease (AD). TPS is using repetitive single ultrashort pulses in the ultrasound frequency range to stimulate the brain. With a neuro-navigation device, TPS can achieve this in a highly focal and precisely targeted manner. TPS differs from DCS and TMS using direct or induced electric current. Instead, TPS provides good spatial precision and resolution to noninvasively modulate subcortical areas, despite the problem of skull attenuation. Using lower ultrasound frequencies TPS can successfully improve skull penetration in humans. TPS has shown its neuroprotective effects through inducing long term neuroplastic changes, supported by neuropsychological tests and neuroimaging investigations both in animal and human studies.
Mild NCD is a golden period for intervention to avoid further progression to dementia. Although TPS has great potential as a new treatment option due to its neuroprotective effects, there is no TPS study done on mild CD subjects according to our knowledge. To determine the effectiveness of TPS in mild NCD, an open-label pilot study was conducted by our team from Dec 2020 to Dec 2021. The preliminary result was presented in the 2021 Brain Stimulation Conference and published in abstract format. We recruited 16 older adults who had mild CD. They received 6 sessions of TPS over 2 weeks.
Assessments were done at the 3 time points. No subjects dropped out during the study. Statistically significant improvement was found in the primary outcome, HK-MoCA, from 18.06 to 20.25. The improvement was maintained till 12 weeks after the TPS intervention. No adverse effect was observed. The result suggested that TPS is likely to have an immediate effect on global cognition in mild CD, and the improvements were sustainable. However, a 2-week treatment duration may not be long enough to induce a significant change in neurodegenerative disease in long term. Up to date, there is no long-term NIBS treatment done on NCD. Therefore, we plan to conduct a pilot case-controlled trial to evaluate the efficacy of long-term TPS on cognition and brain structure in patients with mild ND based on the results of our pilot study.
Objective:
This study is to determine the efficacy of a 24-week program (32 sessions) of TPS in older adults with mild NCD. We hypothesized that TPS group is significantly more effective than control group in maintain or improve the global cognitive function measured by Hong Kong Chinese version of Montreal Cognitive Assessment (HK-MoCA) in patients with mild NCD.
Design:
This case-controlled trial will assess the efficacy of a 24-week TPS program on cognition and brain structure in subjects with mild NCD. All eligible participants will receive an intervention trial of TPS. They would receive 2 sets of stimulation programs, each set lasting 12-weeks. Participants would receive 3 sessions/week in the first 2 weeks and then 1 session/week in the subsequent 10 weeks. A total of 32 sessions (2 sets of 16 sessions) ofTPS will be delivered, with each session lasting 30 minutes.
Data Analysis:
The primary and secondary outcomes will be assessed at baseline, immediately after the 1st set of stimulation program (12th week), 2nd set of stimulation program (24th week), and 12 weeks after the intervention (36th week). The primary outcome will be the change of the Hong Kong Chinese version of the Montreal Cognitive Assessment (HK-MoCA). The secondary outcome includes specific cognitive domains, daily functioning, mood, and apathy. The intention-to-treat analysis would be carried out. Pre and post-intervention brain MRI scans will be used during the intervention to evaluate the changes in brain structure. A checklist of potential adverse effects associated with TPS administration will be generated from the available literature. Blood pressure and heart rate will be recorded at the beginning and at the end of the TPS intervention course.
详细描述
Background:
Dementia, now known as major neurocognitive disorder (NCD), is a great health burden in Hong Kong and worldwide. Interventions that aim to ameliorate cognitive decline or prevent dementia offer a compelling alternative paradigm for reducing the impact of the disease. In principle, to achieve its optimal benefits, intervention for dementia should begin at the earliest preclinical stage, which is defined as mild cognitive impairment (MCI) or mild NCD defined by the 5th Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5).
However, no evidence has been found to support a pharmacological approach to the prevention or postponement of cognitive decline during the stage of mild NCD or MCI (1, 2). Non-invasive brain stimulation (NIBS) is increasingly recognized as a potential alternative to tackle this problem.
The introduction of TPS:
The typical examples of NIBS are transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS). Besides these, there is a new NIBS named transcranial pulse stimulation (TPS), which recently obtained CE marking in 2018 for the treatment of the central nervous system (CNS) in patients with mild to moderate Alzheimer's disease (AD).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •60 years of age or above
- •Chinese ethnicity
- •Fulfil the criteria of mild neurocognitive disorder (NCD), defined by the DSM-5
- •Stable dosage/frequency of anti-dementia therapy or other treatments for mild NCD in recent 8 weeks
- •Valid informed written consent
排除标准
- •HK-MoCA score below the second percentile according to the subject's age and education level (to exclude subjects with existing major NCD/dementia)
- •Alcohol or substance dependence
- •Concomitant unstable major medical conditions or major neurological conditions such as brain tumour, recent stroke
- •Haemophilia or other blood clotting disorders or thrombosis
- •Significant communicative impairments
- •Participants with any metal implant in brain or treated area of the head
结局指标
主要结局
Change in Global Cognition
时间窗: Baseline, at 12 weeks, at 24 weeks, 12-week Follow-up
Global cognitive function measured by the Hong Kong Chinese version of the Montreal Cognitive Assessment (HK-MoCA) ranges from 0 to 30, with higher scores indicating better cognition.
次要结局
- Change in Attention/Working Memory(Baseline, at 12 weeks, at 24 weeks, 12-week Follow-up)
- Change in Brain Structure(Baseline, 12-week Follow-up)
- Change in Memory(Baseline, at 12 weeks, at 24 weeks, 12-week Follow-up)
- Change in Executive Function(Baseline, at 12 weeks, at 24 weeks, 12-week Follow-up)
- Change in Mood(Baseline, at 12 weeks, at 24 weeks, 12-week Follow-up)
- Change in Daily Functioning(Baseline, at 12 weeks, at 24 weeks, 12-week Follow-up)
研究者
Dr. Cheng Pak Wing, Calvin
Clinical Assistant Professor
The University of Hong Kong