Sensory Impairments, Cognitive Decline, and Dementia: What Explains the Association?

感觉障碍、认知衰退和痴呆：如何解释这种关联？

• 批准号: 10382240
• 负责人: Willa Domino Brenowitz
• 金额: $ 13.04万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2023-02-06
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10382240
• 关键词: Adopted; Adult; Affect; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Autopsy; Biological; Biometry; Black Populations; Body Composition; Brain; Brain Pathology; Cardiovascular Diseases; Cerebrovascular Disorders; Clinical; Cognitive; Complement; Complex; Data; Databases; Dementia; Elderly; Epidemiologist; Epidemiology; Foundations; Genetic Risk; Goals; Grant; Health; Hearing; Impaired cognition; Impairment; Intervention; K-Series Research Career Programs; Laboratories; Link; Measurement; Measures; Mediating; Mediator of activation protein; Medical Genetics; Mendelian randomization; Mental Depression; Mentors; Mentorship; Methods; Nature; Nerve Degeneration; Outcome; Participant; Pathway interactions; Physical activity; Population; Presbycusis; Psychosocial Factor; Quality of life; Research; Research Personnel; Research Training; Risk Factors; Role; Sensory; Social isolation; Structure; Training; Training Activity; Treatment/Psychosocial Effects; Vision; Visual impairment; Work; age related; aged; aging brain; biobank; cerebrovascular pathology; clinical predictors; cognitive function; cognitive load; cognitive testing; cohort; comorbidity; cost effective; dementia risk; effective therapy; hearing impairment; improved; innovation; insight; modifiable risk; multidisciplinary; multiple datasets; normal aging; novel; novel strategies; physical inactivity; population based; pre-clinical; prevent; programs; psychosocial; psychosocial wellbeing; sex; skills; study population; tool

PROJECT SUMMARY Given the lack of effective treatments for Alzheimer’s disease (AD) and related dementias (ADRD), identification of modifiable risk factors is critical. Sensory impairments may affect over 50% of adults aged 65 years and older and have been linked to Alzheimer’s disease (AD) and related dementias (ADRD). However, the nature of this association in diverse aging populations is not well understood. Furthermore, the underlying pathways and mechanisms for why hearing and visual impairments predict dementia are unclear. Hearing and visual impairments are hypothesized to 1.) directly impact brain structure and function to accelerate cognitive decline, 2.) indirectly influence cognitive decline due to links to other dementia risk factors such as psychosocial factors, or 3.) represent underlying neurodegeneration or cardiovascular disease. The scientific goal of this study is to adopt a systematic approach to evaluate the role of hearing and visual impairments in cognitive decline and risk of dementia as well as to identify mechanisms that explain the relationship. This project focuses on hearing and visual impairments as these have the greatest effect on quality of life and high potential for treatment or correction. In a feasible and cost-effective approach, this project will leverage three existing and complementary studies of aging that have measures of sensory and cognitive function: The Health Aging and Body Composition Study, a 15-year population-based cohort of 3,075 black and white adults in the U.S; the National Alzheimer’s Coordinating Center, a database of US Alzheimer’s Disease Center participants including autopsy findings; and The UK Biobank, a study of 500,000 UK adults with clinical and genetic data. Innovative and rigorous epidemiologic approaches will be applied to conduct 1.) a study of diverse older adults using objective measures of hearing and visual impairments and 2.) a Mendelian Randomization analysis, a novel approach to enhance causal inference, as well as studies to determine whether associations are explained by 3.) underlying neuropathologic mechanisms or by 4.) psychosocial mediators. The research plan in this mentored career development award is complemented by training activities that build on the candidate’s background in epidemiology and provides new training in a.) clinical dementia assessment, b.) advanced casual inference methods, and c.) age-related hearing and visual impairments. Together the candidate’s research aims, training activities, and guidance from a multidisciplinary mentorship team will allow the candidate to develop a successful independent research program examining the relationship between sensory impairments and ADRD. The current research plan is expected to provide critical insight into what factors and mechanisms can explain the associations between sensory impairment and ADRD. These findings will inform whether sensory impairments or their downstream psychosocial effects can be used as targets for intervention to prevent dementia, or whether sensory impairments can be used as clinical predictors for identifying preclinical AD or cerebrovascular disease.

项目摘要 由于缺乏有效的治疗阿尔茨海默病（AD）和相关痴呆症（ADRD）， 确定可改变的风险因素至关重要。感觉障碍可能影响超过50%的65岁成年人 年龄和年龄更大，并与阿尔茨海默病（AD）和相关痴呆症（ADRD）有关。然而，在这方面， 在不同的老龄人口中，这种关联的性质还没有得到很好的理解。此外，底层 听觉和视觉障碍预测痴呆症的途径和机制尚不清楚。听力和 视觉障碍被假设为1。直接影响大脑结构和功能， 下降，2.）由于与其他痴呆症风险因素的联系， 社会心理因素，或3.）代表潜在的神经退化或心血管疾病。科学 本研究的目的是采用一种系统的方法来评估听力和视力障碍在 认知能力下降和痴呆症的风险，以及确定解释这种关系的机制。这 该项目侧重于听力和视力障碍，因为这些对生活质量影响最大， 治疗或纠正的可能性。在一个可行和具有成本效益的方法中，该项目将利用三个 现有的和补充的衰老研究，有感官和认知功能的措施：健康 衰老和身体成分研究，一项为期15年的基于人群的队列研究，包括3,075名黑人和白色成年人， 美国国家老年痴呆症协调中心，美国老年痴呆症中心参与者的数据库 包括尸检结果;英国生物银行，一项对50万英国成年人的临床和遗传数据的研究。 创新和严格的流行病学方法将应用于进行1。一项针对不同老年人的研究 使用听力和视力障碍的客观措施，以及2.）a孟德尔随机化分析， 新的方法，以加强因果推理，以及研究，以确定是否协会是 解释3）。潜在的神经病理机制或4.）心理社会调解员研究计划 在这个指导职业发展奖是由培训活动，建立在候选人的补充 流行病学背景，并提供新的培训a.）临床痴呆评估，B.）先进 因果推理方法，以及c.）与年龄有关的听力和视力障碍。候选人的 研究目标，培训活动和多学科导师团队的指导将使 候选人制定一个成功的独立研究计划，研究感官之间的关系 损伤和ADRD。目前的研究计划预计将提供关键的洞察力，什么因素， 机制可以解释感觉障碍和ADRD之间的关联。这些发现将为 感觉障碍或其下游的心理社会影响是否可以作为干预的目标 以预防痴呆症，或者感觉障碍是否可以作为临床预测因素， 临床前AD或脑血管疾病。