Mechanisms Linking Hearing Loss and Alzheimer's Disease and Related Dementias

听力损失与阿尔茨海默病及相关痴呆症的联系机制

• 批准号: 9895606
• 负责人: Justin Scott Golub
• 金额: $ 16.52万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-15 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9895606
• 关键词: Academic Medical Centers; Address; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-Protein; Ancillary Study; Area; Award; Biological Markers; Biometry; Brain; Brain imaging; Categories; Cerebrovascular Disorders; Chronic; Cognition; Cognitive; Color; Complication; Data; Data Collection; Development; Discipline; Disease; Education; Elderly; Epidemiology; Family; Future; Geriatrics; Goals; Head and Neck Surgery; Hearing; Hearing Tests; Hispanics; Impaired cognition; Infarction; Inferior; K-Series Research Career Programs; Knowledge; Lead; Learning; Life; Link; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Medial; Mediating; Mediation; Memory; Mentored Patient-Oriented Research Career Development Award; Mentors; Methods; Nerve Degeneration; Neurocognitive; Neuropsychology; Not Hispanic or Latino; Otolaryngology; Outcome; Performance; Persons; Positron-Emission Tomography; Presbycusis; Prevalence; Principal Investigator; Pure-Tone Audiometry; Reporting; Research; Research Project Grants; Risk; Standardization; Temporal Lobe; Testing; Training; White Matter Hyperintensity; aging brain; brain volume; career; career development; cerebral atrophy; cognitive performance; cognitive testing; cohort; dementia risk; ethnic minority population; executive function; experience; hearing impairment; high risk; imaging biomarker; meetings; middle age; neuroimaging; patient oriented research; prevent; professor; responsible research conduct; sex; tau Proteins; tool; uptake

The proposed K23 award will provide Justin S. Golub, MD, an assistant professor of otolaryngology—head and neck surgery at Columbia University Medical Center, with mentored career development to establish an independent research career in the study of the relation of hearing loss (HL) to Alzheimer’s disease (AD) and related dementias (ADRD). Age-related HL is the third most common chronic condition in older adults and is associated with ADRD, cognitive decline, and brain atrophy. However, the mechanisms underlying these associations are unknown. The goal of this career development award is to advance Dr. Golub’s research career in HL and ADRD by (a) providing mentored career development and training in patient-oriented research (POR); and b) conducting research to elucidate the mechanisms underlying the association of HL with ADRD in an ancillary study of an ongoing project, in which the primary mentor, José Luchsinger, is the principal investigator. This project will inform the development of future POR in HL and ADRD. Career development will be provided through an experienced team of mentors spanning the disciplines of aging, geriatrics, neuropsychology, neuroimaging, epidemiology, and otolaryngology. Training will occur in 6 key areas: (1) aging and ADRD; (2) implementing hearing assessments in POR; (3) brain imaging; (4) cognitive testing; (5) biostatistics and epidemiology related to POR in ADRD; (6) professional development. Modes of learning will include meetings with mentors, formal courses in career development, formal courses in epidemiology and biostatistics, seminars in aging and ADRD, training and participation in primary data collection, scientific meetings, and training in the responsible conduct of research. Preliminary studies from the applicant revealed a 70% increased risk of ADRD in the elderly with observed (not measured) HL compared with those without observed HL. The research goal of this award is to examine the associations of objectively measured HL with imaging markers of ADRD and cognitive performance in late middle aged persons. This will be the first step towards elucidating the mechanisms of the association between age-related HL and ADRD. We will accomplish this by adding an audiometric hearing test to an existing longitudinal study of imaging markers of ADRD in late middle age. This study includes longitudinal ascertainment of AD, neurodegeneration, and cerebrovascular disease (CVD) on brain imaging, as well as cognition. AD is ascertained as whole brain amyloid β with 18F-Florbetaben positron emission tomography (PET). Neurodegeneration is ascertained as tau in inferior and medial temporal lobes with 18F-THK5351 PET, and brain atrophy with magnetic resonance imaging (MRI). CVD is ascertained as white matter hyperintensities and infarcts on MRI. Cognitive testing includes memory and executive function. We hypothesize that HL is associated with AD, neurodegeneration, and CVD, and these associations mediate the association between HL and worse cognitive performance. The proposed career development activities and research project will help propel a career to clarify whether HL is a cause, consequence, or correlate of ADRD.

拟议的K23奖将为耳鼻喉科助理​​教授Justin S. Golub提供 哥伦比亚大学医学中心的颈部手术，并为职业发展提供了指导 独立的研究职业在研究听力损失（HL）与阿尔茨海默氏病（AD）和 相关痴呆症（ADRD）。与年龄有关的HL是老年人中第三大常见的慢性病，​​是 与ADRD相关，认知能力下降和大脑萎缩。但是，这些机制是这些机制 关联是未知的。这个职业发展奖的目标是促进Golub博士的研究生涯 （a）在HL和ADRD中提供了指导的职业发展和以患者为导向的研究（POR）； b）进行研究以阐明HL与ADRD关联的基础机制 对正在进行的项目的辅助研究，其中主要导师何塞·卢切辛格（JoséLuchsinger）是主要研究者。 该项目将为HL和ADRD的未来POR的发展提供信息。将提供职业发展 通过经验丰富的导师团队，涵盖衰老，老年医学，神经心理学， 神经影像学，流行病学和耳效界学。培训将在6个关键领域进行：（1）衰老和ADRD； （2） 在POR中实施听力评估； （3）大脑成像； （4）认知测试； （5）生物统计学和 与ADRD的POR有关的流行病学； （6）专业发展。学习模式将包括会议 凭借其精神，职业发展的正式课程，流行病学和生物统计学的正式课程 在衰老和ADRD中，培训和参与主要数据收集，科学会议以及培训 负责任的研究。适用的初步研究显示，ADRD的风险增加了70％ 与未观察到的HL相比，在原处观察到的HL（未测量）HL。研究目标的 该奖项是为了检查客观测量的HL与ADRD和ADRD的成像标记的关联 中年晚年的认知表现。这将是阐明机制的第一步 与年龄有关的HL和ADRD之间的关联。我们将通过添加听力听证会来实现这一目标 测试中期晚期ADRD成像标记的现有纵向研究。这项研究包括 脑成像的AD，神经退行性和脑血管疾病（CVD）的纵向确定 以及认知。 AD被确定为全脑淀粉样β与18F叶绿素的正电子发射断层扫描 （宠物）。神经变性被确定为tau tau，在次要和媒体临时爱上，用18f-thk5351宠物， 带有磁共振成像（MRI）的脑萎缩。 CVD被确定为白质超强度 并在MRI上出现。认知测试包括内存和执行功能。我们假设HL是 与AD，神经变性和CVD相关，这些关联介导HL之间的关联 而且认知表现较差。拟议的职业发展活动和研究项目将有助于 推动职业澄清HL是ADRD的原因，结果还是相关。