Transcranial Photobiomodulation for Alzheimer's Disease (TRAP-AD)

项目总结 阿尔茨海默病(AD)的患病率预计将随着人口老龄化而增加，目前 治疗效果微乎其微。最近，人们强调了对疾病的认识和治疗 探讨影响早期脑病理的因素，以延缓AD的最终临床表现。 近红外光的经颅光生物调节(t-PBM)能很好地穿透大脑。 大脑皮质，刺激线粒体呼吸链，也显著增加脑血流量 (CBF)。早期数据提示t-PBM可能在改善早期AD和AD患者的认知功能障碍方面有效 遗忘性轻度认知障碍(AMCI)。该项目旨在通过随机对照试验来测试 持续8周的24次t-PBM的有效性和安全性，并与假手术相比，在改善 急性心肌梗死的临床症状。此外，我们还将通过测试来探讨t-pbm在aMCI中的脑机制。 基线tau负荷(用18F-MK6240测量)或线粒体功能指标的变化 8周以上(由31P-MRSI测量)缓和了t-PBM后观察到的认知功能的变化 心理治疗。我们还将使用单一治疗后fMRI血氧水平依赖(BOLD)的变化， 证明t-PBM依赖的前额叶皮质(PFC)皮质血流量(CBF)增加。这项研究将 在纽约大学、内森·克莱恩研究所和马萨诸塞州综合医院同时进行。这个 本研究的重要性有三：(1)针对AD的一个重要的前驱阶段--aMCI，它缺乏 充分批准的治疗，(2)它评估t-pbm的有效性和安全性，t-pbm是一种创新的、非侵入性的 一种具有良好安全性的技术，用于改善大脑功能和认知能力 前驱AD分期，以及，(3)探索t-PBM治疗效果与重要生物标志物的关系 与AD疾病进展相关。如果效果得到证实，本研究将既支持短期 一种易于扩展的治疗aMCI和AD的设备的临床开发，同时也进行了验证 未来发展的生物标志物，新颖的调控策略。

PROJECT SUMMARY The prevalence of Alzheimer disease (AD) is projected to increase as the population ages, and current treatments are only minimally effective. Recently, emphasis has been placed on understanding and treating the factors that influence early brain pathology in order to slow the ultimate clinical expression of AD. Transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light penetrates robustly into the cerebral cortex, stimulating the mitochondrial respiratory chain, and also significantly increases cerebral blood flow (CBF). Early data suggests t-PBM may be efficacious in improving cognitive deficits in early AD and in amnestic mild cognitive impairment (aMCI). This project aims to test, in a randomized controlled trial, the efficacy and safety of 24 sessions of t-PBM, delivered over 8 weeks and compared to sham, in improving clinical symptoms of aMCI. Additionally, we will explore the brain mechanisms of t-PBM in aMCI, by testing whether baseline tau burden (measured with 18F-MK6240), or changes in mitochondrial function measures over 8 weeks (measured by 31P-MRSI) moderate the changes observed in cognitive functions after t-PBM therapy. We will also use changes in fMRI blood-oxygenation-level dependent (BOLD) after a single treatment, to demonstrate t-PBM-dependent increases in prefrontal cortex (PFC) cortical blood flow (CBF). The study will be done in parallel at New York University, Nathan Kline Institute and at Massachusetts General Hospital. The importance of this study is threefold: (1) it targets aMCI, an important prodromal stage of AD, which lacks adequate approved treatments, (2) it evaluates the efficacy and safety of t-PBM, an innovative, non-invasive technology which has a well-established safety profile, for improving brain function and cognition at the prodromal AD stages, and, (3) explores the association of t-PBM treatment effects with important biomarkers relevant for AD illness progression. If effects are confirmed, the present study will both support short-term clinical development of an easy to scale device for the treatment of aMCI and AD, while also validating biomarkers for the development of future, novel modulation strategies.