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奖项将为贾斯汀·S·戈卢布医学博士、耳鼻喉科助理教授兼主任和 在哥伦比亚大学医学中心接受颈部外科手术，并在职业发展指导下建立 在研究听力损失(HL)与阿尔茨海默病(AD)和 相关痴呆(ADRD)。与年龄相关的HL是老年人中第三常见的慢性疾病， 与ADRD、认知衰退和脑萎缩有关。然而，这些问题背后的机制 联想是未知的。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，通过(A)在以患者为导向的研究(POR)方面提供有指导的职业发展和培训； 和b)进行研究，以阐明急性白血病与急性呼吸窘迫综合征相关的潜在机制 对一个正在进行的项目进行的辅助研究，其中主要导师何塞·卢辛格是首席研究员。 该项目将为HL和ADRD未来POR的发展提供信息。将提供职业发展方面的服务 通过一支经验丰富的导师团队，他们涵盖了老年学、老年病学、神经心理学、 神经影像、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中与POR相关的流行病学；(6)职业发展。学习方式将包括会议 有导师、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、科学会议和培训 负责任的研究行为。申请者的初步研究显示，ADRD的风险增加了70% 观察到(未测量)HL的老年人与未观察到HL的老年人比较。的研究目标 该奖项旨在研究客观测量的HL与ADRD和ADRD的成像标记物之间的关系 中老年人群的认知表现。这将是阐明这些机制的第一步。 年龄相关性HL和ADRD之间的联系。我们将通过添加听力听证来实现这一点 对已有的中年晚期ADRD影像标志物的纵向研究进行检验。这项研究包括 在脑成像上纵向确定AD、神经退行性变和脑血管疾病(CVD)，AS 以及认知力。18F-弗洛贝塔本正电子发射断层扫描证实AD为全脑淀粉样蛋白β (宠物)。18F-THK5351正电子发射计算机断层扫描证实下、内侧颞叶神经变性为tau。 以及磁共振成像(MRI)显示的脑萎缩。脑血管病确诊为脑白质高信号 核磁共振显示有梗死灶。认知测试包括记忆和执行功能。我们假设HL是 与阿尔茨海默病、神经退行性变和心血管疾病相关，这些关联介导了HL之间的关联 以及较差的认知表现。拟议的职业发展活动和研究项目将有所帮助 推动职业生涯，澄清HL是ADRD的原因、后果还是相关因素。