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: 10396525
• 负责人: Justin Scott Golub
• 金额: $ 16.43万
• 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 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10396525
• 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; Hispanic Populations; 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 magnetic resonance imaging; brain volume; career; career development; cerebral atrophy; cognitive performance; cognitive testing; cohort; dementia risk; ethnic minority; 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 奖项将提供贾斯汀·S·戈卢布 (Justin S. Golub) 医学博士，他是耳鼻喉科助理​​教授 — 主任和 哥伦比亚大学医学中心的颈部手术，并指导职业发展以建立 独立研究生涯，研究听力损失（HL）与阿尔茨海默病（AD）的关系 相关性痴呆 (ADRD) 是老年人中第三大常见的慢性疾病。 与 ADRD、认知能力下降和脑萎缩有关，然而，这些背后的机制。 该职业发展奖的目标是推进戈卢布博士的研究生涯。 在 HL 和 ADRD 领域，通过 (a) 提供有指导的职业发展和以患者为导向的研究 (POR) 培训； b) 进行研究以阐明 HL 与 ADRD 关联的潜在机制 一个正在进行的项目的辅助研究，其中主要导师 José Luchsinger 是首席研究员。 该项目将为 HL 和 ADRD 未来 POR 的发展提供信息。 通过经验丰富的导师团队，涵盖衰老、老年病学、神经心理学、 培训将在 6 个关键领域进行：(1) 老龄化和 ADRD；(2) 神经影像学、流行病学和耳鼻喉科。 在 POR 中实施听力评估；(3) 脑成像；(5) 生物统计学； ADRD 中与 POR 相关的流行病学；(6) 专业发展模式将包括会议。 与导师一起，职业发展的正式课程，流行病学和生物统计学的正式课程，研讨会 老龄化和 ADRD 方面的培训和参与主要数据收集、科学会议以及 申请人进行的负责任的研究表明，ADRD 风险增加了 70%。 观察到（未测量）HL 的老年人与未观察到 HL 的老年人进行比较。 该奖项旨在检查客观测量的 HL 与 ADRD 和影像学标志物之间的关联 这将是阐明其机制的第一步。 我们将通过增加听力测试来实现这一目标。 这项研究包括对中年晚期 ADRD 影像学标志物的现有纵向研究的检验。 通过脑成像纵向确定 AD、神经退行性疾病和脑血管疾病 (CVD)，如 AD 被确定为全脑淀粉样蛋白 18F-Florbetaben 正电子发射断层扫描。 (PET) 使用 18F-THK5351 PET 确定下颞叶和内侧颞叶中的 tau 蛋白， 磁共振成像 (MRI) 确定脑萎缩为白质高信号。 MRI 上的梗塞认知测试包括记忆和执行功能。 与 AD、神经退行性疾病和 CVD 相关，这些关联介导 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 是否是 ADRD 的原因、结果或相关性。

项目成果

Hearing Aid Usage and Reported Hearing Difficulty in Americans With Subclinical Hearing Loss.

患有亚临床听力损失的美国人的助听器使用情况和报告的听力困难。

• DOI: 10.1097/mao.0000000000003683
• 发表时间: 2022
• 期刊: Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
• 作者: Dragon,JacquelineM;Grewal,MaeherR;Irace,AlexandriaL;Golub,JustinS
• 通讯作者: Golub,JustinS

Prevalence of Single-Sided Deafness in the United States.

• DOI: 10.1002/lary.29941
• 发表时间: 2022-08
• 期刊: LARYNGOSCOPE
• 影响因子: 2.6
• 作者: Kay-Rivest, Emily;Irace, Alexandria L.;Golub, Justin S.;Svirsky, Mario A.
• 通讯作者: Svirsky, Mario A.

The Association Between Early Age-Related Hearing Loss and Brain β-Amyloid.

早期年龄相关性听力损失与大脑 β-淀粉样蛋白之间的关联。

• DOI: 10.1002/lary.28859
• 发表时间: 2021-03
• 期刊: The Laryngoscope
• 作者: Golub JS;Sharma RK;Rippon BQ;Brickman AM;Luchsinger JA
• 通讯作者: Luchsinger JA

The Laterality of Age-Related Hearing Loss and Depression.

• DOI: 10.1097/mao.0000000000003531
• 发表时间: 2022-07-01
• 期刊: OTOLOGY & NEUROTOLOGY
• 影响因子: 2.1
• 作者: Chern, Alexander;Irace, Alexandria L.;Golub, Justin S.
• 通讯作者: Golub, Justin S.

Prevalence of Subclinical Hearing Loss in the United States.

美国亚临床听力损失的患病率。

• DOI: 10.1002/ohn.326
• 发表时间: 2023
• 期刊: Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery
• 作者: Dragon,JacquelineM;Grewal,MaeherR;Irace,AlexandriaL;GarciaMorales,Emmanuel;Golub,JustinS
• 通讯作者: Golub,JustinS