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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.

摘要