Revitalizing Cognition in Older Adults at Risk for Alzheimer's Disease with Near-Infrared Photobiomodulation

通过近红外光生物调节恢复有阿尔茨海默病风险的老年人的认知能力

基本信息

批准号：
10400849
负责人：
GENE E ALEXANDER
金额：
$ 79.81万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10400849
关键词：
Adenosine Triphosphate Age Age-associated memory impairment Alzheimer&apos s Disease Alzheimer&apos s disease model Alzheimer&apos s disease risk Amyloid beta-Protein Animal Model Animals Aphasia Apolipoproteins Arizona Behavioral Blood Vessels Brain Cell model Cognition Cognitive Controlled Clinical Trials Data Dementia Diabetes Mellitus Disease Double-Blind Method Education Elderly Episodic memory Exposure to Family history of Florida Functional Magnetic Resonance Imaging Future Gender Genetic Goals Hippocampus (Brain)Home Human Hypertension Impaired cognition Individual Individual Differences Intervention Lesion Light Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Measures Medial Mediating Memory Metabolic Metabolism Mitochondria Moods Neurofibrillary Tangles Outcome Outcome Measure Performance Phase Phase II Clinical Trials Phosphorus Population Prevalence Prevention therapy Production Protocols documentation Public Health Randomized Randomized Clinical Trials Reporting Research Rest Risk Risk Factors Short-Term Memory Site Stroke Temporal Lobe Testing Therapeutic Intervention Transgenic Mice Traumatic Brain Injury United States National Institutes of Health Universities amnestic mild cognitive impairment analog base brain health cognitive function cognitive performance cost effective intervention effective therapy executive function experience follow-up functional decline improved insight morris water maze multi-component intervention neural network neuroimaging novel photobiomodulation post intervention prevent primary outcome prophylactic response treatment group vascular risk factor way finding white matter young adult

项目摘要

ABSTRACT There is a great need for effective treatments and prevention therapies that can provide symptomatic and disease modifying benefits for those at risk for Alzheimer’s disease. The proposed multi-site collaborative project brings together research teams at the University of Florida (UF) and University of Arizona (UA) to test a novel, relatively low cost, low risk, and potentially high impact therapeutic intervention in older adults who are at increased risk for Alzheimer’s disease. The intervention involves transcranial and intranasal delivery of near infrared (NIR) light via light emitting diodes, aka photobiomodulation. Prior research in cellular and animal models suggest that red and infrared light are neuroprotective and thought to improve mitochondrial function by promoting increased production of intracellular ATP. Transgenic mouse models of Alzheimer’s disease demonstrate reduced beta-amyloid and neurofibrillary tangles in response to transcranial NIR versus sham stimulation. Preliminary human studies have also shown promising behavioral findings in young adults and those with TBI, aphasia, and Alzheimer’s disease. From our team, pilot phosphorous magnetic resonance spectroscopy (31P MRS) and cognitive data in older adults support this mechanism of action and provide compelling evidence for a Phase II clinical trial. To more fully determine whether this novel stimulation approach has potential for enhancing cognition in cognitively normal but “at risk” individuals for Alzheimer’s disease, we plan to conduct a multi-site double blinded randomized sham-controlled Phase II clinical trial. Our overall hypothesis is that exposure to NIR stimulation will have beneficial effects on brain health via influence on mitochondrial function as measured by changes in 31P MRS-based markers of ATP, neural network changes in functional connectivity (rs-fMRI), and improved cognitive performance. To test this hypothesis, we plan to randomize 168 older adults with subjective cognitive complaints, and a first-degree family history of Alzheimer’s disease to sham or real treatment groups and evaluate neuroimaging and cognitive outcome measures, before and after a 12-week intervention involving transcranial and intranasal NIR-PBM. The protocol will involve “lab” and “home” sessions, and a 3 month post-intervention follow-up. This trial will determine: 1) whether NIR stimulation, relative to sham, improves performance on memory and executive tasks sensitive to hippocampal and frontal brain function in older adults with increased risk for Alzheimer’s disease; 2) whether NIR stimulation, relative to sham, enhances brain function and connectivity measured by changes in MRS phosphorous ATP and resting state functional connectivity; and 3) how differences in demographic, neuroimaging, and Alzheimer-related risk factors influence the brain response to NIR stimulation versus sham in older adults with increased risk for Alzheimer’s disease. Results will provide key insights into whether this novel NIR intervention can enhance cognition in older adults with increased risk for Alzheimer’s disease and will provide the necessary data for a future Phase III randomized clinical trial.

抽象的非常需要有效治疗和预防疗法，可以提供症状和为患有阿尔茨海默氏病风险的人改变疾病的益处。拟议的多站点合作项目汇集了佛罗里达大学（UF）和亚利桑那大学（UA）的研究团队，以测试新颖的，相对较低的成本，低风险和潜在的高影响热干预的老年人阿尔茨海默氏病的风险增加。干预涉及接近的经颅和鼻内递送红外（NIR）通过发光二极管，又称光生物调节。先前的细胞和动物研究模型表明红色和红外光具有神经保护作用，并认为可以改善线粒体功能通过促进细胞内ATP的产生增加。阿尔茨海默氏病的转基因小鼠模型证明对thrancranial NIR与假的响应刺激。初步的人类研究还显示了年轻人和患有TBI，失语症和阿尔茨海默氏病的人。从我们的团队中，试点磷磁共振老年人的光谱法（31p MRS）和认知数据支持这种作用机理并提供令人信服的II期临床试验证据。更充分地确定这种新颖的刺激是否方法具有增强认知正常的认知的潜力疾病，我们计划进行一项多站点双盲随机假手术II期临床试验。我们的总体假设是，接触NIR刺激将对大脑健康产生有益的影响关于通过基于ATP的31p MRS标记，神经网络的31p MRS标记来衡量的线粒体功能功能连接性（RS-FMRI）的变化，并提高了认知性能。为了检验这一假设，我们计划将168名具有主观认知投诉的老年人随机，以及一级家族史阿尔茨海默氏病对假或真实治疗组的疾病，并评估神经影像学和认知结果在涉及经颅内和鼻内NIR-PBM的12周干预之前和之后进行的措施。协议将涉及“实验室”和“家庭”会议，并在干预后3个月进行随访。这个审判将确定：1）NIR刺激是否相对于假手术，是否可以提高记忆和执行的表现对老年人的海马和额叶脑功能敏感的任务，阿尔茨海默氏症风险增加疾病; 2）NIR刺激是否相对于假手术增强了大脑功能和连通性 MRS磷ATP和静息状态功能连通性的变化； 3）如何差异人口统计学，神经影像学和与阿尔茨海默氏症相关的危险因素影响大脑对NIR刺激的反应在老年人中，患有阿尔茨海默氏病风险增加的老年人。结果将为您提供关键的见解这种新颖的NIR干预是否可以增强老年人的认知，而阿尔茨海默氏症风险增加疾病，将为未来的III期随机临床试验提供必要的数据。