Transcranial Pulse Stimulation Open-label Self-controlled Trial For Mild Neurocognitive Disorder

Background: A significant proportion of older adults suffered from age-related diseases particularly dementia, also known as major neurocognitive disorder (NCD), which is becoming a worldwide health burden. In principle, Interventions for dementia should have optimal benefits at the earliest preclinical stage yet no evidence has been found to support a particular pharmacological approach in preventing cognitive decline during the stage of mild NCD. Non-invasive brain stimulation (NIBS), on the other hand, is increasingly recognized as a potential alternative to tackle this problem. Typical NIBS include transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS). A new kind of NIBS named Transcranial Pulse stimulation (TPS) is also recently used for treating patients with Alzheimer's disease (AD).TPS is a kind of NIBS that uses repetitive sin ultrashort pulses in the ultrasound frequency range to stimulate the brain, and it can provide better spatial precision and reach deeper brain regions comparing to tDCS and TMS. The mechanism of TPS is to convert the mechanical TPS stimulus into biochemical responses, thus influence some fundamental cell functions. A recent study showed that there is a significant improvement in using TPS in treating AD. However, there has been no study investigating the effect of TPS on older adults with mild NCD. Objective: This study is an open-label self-controlled study to assess the effectiveness and tolerability of TPS on cognition in older adults with mild NCD. We hypothesized that a 2-week TPS intervention could significantly improve patient's global cognition which will be maintained for 12 weeks. Design: The current study is an open-label self-controlled interventional trial of TPS guided by neuro-navigation using structural MRI. All participants will undergo the treatment as usual (TAU) period as self-controlled for 12 weeks. They will then receive a six-session TPS intervention for 2 weeks with th