Interleaved TMS-fMRI for Hippocampal Stimulation: Modeling Dose-Response Relationship in Amnestic Mild Cognitive Impairment
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 2
- 主要终点
- Correction Rate in Memory Association Recall
研究概览
简要总结
Emerging evidence indicates that dysfunction of hippocampal synaptic plasticity, which precedes neuronal degeneration during the progression of Alzheimer's disease (AD), underlies the hallmark cognitive impairment. Although there are currently no effective disease modifying treatments for AD, recent preclinical studies in animal models of AD have suggested that repetitive transcranial magnetic stimulation (rTMS) promotes hippocampal synaptic plasticity and, ultimately, improves learning and memory abilities. Interleaved TBS-MRI is a paradigm, which allows the investigators to study human brain functionality with real-time MRI, to better understand modulations of brain activity in response to the non-invasive brain stimulation, TBS. The interleaved TBSfMRI paradigm can more accurately estimated the immediate brain activity compared to the offline TBS-MRI studies in which TBS is applied outside the MRI. With this interleaved TBS-MRI approach, the investigators will be able to measure immediate changes in targeted brain activity, such as hippocampus activation, following each TBS session. This approach has created the unprecedented potential enabling the investigators to model the dose-dependent effects of TBS more accurately on brain function.
详细描述
The overarching goal of this proposed project is to maximize TBS effects to non-invasive spaced TBS in MCI. For the comparison, the investigators will include cognitively normal adults. There will be a screening session plus three consecutive days including baseline outcome measures on Day 1, TMS interventions and outcome measures on Day 2, and follow-up measurements on Day 3. In this project, on Day 2, participants will receive three TBS blocks inside the MRI scanner with each TBS block separated by 30-90 minutes to enhance the possibility of maximizing the TBS effect. This will be repeated in two blocks, each with a different TMS protocol. The protocols will be in randomized order.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 50-80 years
- •MCI clinical criteria: (a) self- or informant-reported cognitive complaint; (b) preserved independence in functional abilities; and (c) absence of dementia.
- •Objective cognitive impairment supported by the following measures of general cognitive function: (a) Mini-Mental State Exam (MMSE) 24-27 (inclusive); (b) Montreal Cognitive Assessment (MoCA) 18-26 (inclusive); or (c) Clinical Dementia Rating Scale score of 0.
- •Right handed
- •English speaking
- •Able to attend daily intervention (Monday-Friday) for 4 days
- •Not enrolled in another interventional study within 6 months prior to beginning this study
排除标准
- •Contraindications to transcranial magnetic stimulation (TMS) or magnetic resonance imaging (MRI)
- •Other neurological disorders (e.g. stroke, head injuries, or multiple sclerosis)
- •Untreated depression
- •Current cancer treatment or other medical problems that might independently affect cognitive function
- •Clinical Dementia Rating Scale score more than 1.0
结局指标
主要结局
Correction Rate in Memory Association Recall
时间窗: Immediately after intervention day (block 1 day 2) and (block 2 day 2) vs. Baseline
Memory tasks will be implemented and measure the correct rate to assess memory function. The scale is the Face Name Associated Memory Score, and the min/max values are 0-1. A higher score indicates a better outcome.
次要结局
未报告次要终点
研究者
Ying-hui Chou
Principle Investigator
University of Arizona