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

拟议的K23奖将提供贾斯汀S。Golub，医学博士，耳鼻喉科助理教授， 在哥伦比亚大学医学中心的颈部手术，与指导的职业发展，建立一个 独立研究听力损失（HL）与阿尔茨海默病（AD）的关系， 相关性痴呆（ADRD）HL相关性HL是老年人中第三常见的慢性疾病， 与ADRD、认知能力下降和脑萎缩相关。然而，这些潜在的机制 协会是未知的。这个职业发展奖的目标是推进戈卢布博士的研究事业 在HL和ADRD中，通过（a）在以患者为导向的研究（POR）中提供指导性职业发展和培训; 和B）进行研究，以阐明HL与ADRD相关的潜在机制， 正在进行的项目的辅助研究，其中主要导师José Luchsinger是主要研究者。 该项目将为HL和ADRD未来POR的发展提供信息。将提供职业发展 通过一个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鼻喉科培训将在6个关键领域进行：（1）老龄化和ADRD;（2） 在POR中实施听力评估;（3）脑成像;（4）认知测试;（5）生物统计学和 ADRD中POR相关的流行病学;（6）专业发展。学习方式将包括会议 与导师、职业发展正式课程、流行病学和生物统计学正式课程、研讨会 在老龄化和ADRD方面，培训和参与初级数据收集、科学会议以及 负责任地进行研究。申请人的初步研究显示，ADRD风险增加70% 与未观察到HL的老年人相比，观察到（未测量）HL的老年人。的研究目标 该奖项旨在研究客观测量的HL与ADRD的影像学标志物的相关性， 中年后期的认知表现。这将是阐明机制的第一步 年龄相关HL和ADRD之间的关联。我们将通过增加听力测试来实现这一点 对现有的中年晚期ADRD影像学标志物的纵向研究进行检验。本研究包括 在脑成像上纵向确定AD、神经变性和脑血管疾病（CVD）， 以及认知。用18F-Florbetaben正电子发射断层扫描确定AD为全脑淀粉样β蛋白 （PET）。用18F-THK 5351 PET确定神经变性为下颞叶和内侧颞叶中的tau， 和脑萎缩的磁共振成像（MRI）。CVD被确定为白色高信号 和脑梗塞的症状认知测试包括记忆和执行功能。我们假设HL是 与AD、神经退行性变和CVD相关，这些相关性介导了HL 和更差的认知表现。拟议的职业发展活动和研究项目将有助于 推动职业生涯，以澄清HL是否是ADRD的原因，后果或相关性。

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.