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

项目总结 鉴于阿尔茨海默病(AD)和相关痴呆症(ADRD)缺乏有效的治疗方法， 确定可更改的风险因素至关重要。超过50%的65岁成年人可能会受到感觉障碍的影响 与阿尔茨海默病(AD)和相关痴呆症(ADRD)有关。然而， 在不同的老龄化人口中，这种关联的性质还没有被很好地理解。此外，潜在的 听力和视觉障碍预测痴呆症的途径和机制尚不清楚。听证和 视力障碍假设为1。)直接影响大脑结构和功能，加速认知 拒绝，2。)由于与其他痴呆症风险因素有关，间接影响认知能力下降 心理社会因素，或3.)代表潜在的神经变性或心血管疾病。科学的 这项研究的目标是采用系统的方法来评估听力和视觉障碍在 认知衰退和痴呆症的风险，以及确定解释这种关系的机制。这 该项目重点关注听力和视觉障碍，因为这些对生活质量的影响最大， 治疗或矫正的可能性。在一种可行和具有成本效益的方法中，该项目将利用三个 测量感觉和认知功能的现有的和补充的衰老研究：健康 老龄化和身体成分研究，一项为期15年的基于人口的队列，其中包括3075名黑人和白人成年人 美国国家阿尔茨海默氏症协调中心，美国阿尔茨海默病中心参与者的数据库 包括尸检结果；以及英国生物库，一项对50万名英国成年人进行的临床和基因数据研究。 将采用创新和严格的流行病学方法开展1.)一项针对不同老年人的研究 使用听力和视觉障碍的客观测量和2.)孟德尔随机化分析，一个 增强因果推理的新方法，以及确定关联是否 由3解释。)潜在的神经病理机制或4。)心理社会调解人。研究计划 在这个辅导式职业发展奖中，辅以培训活动，这些活动建立在候选人 具有流行病学背景，并提供新的培训。)临床痴呆评估，b.)高级 因果推理方法，以及c.)与年龄相关的听力和视觉障碍。把候选人的 多学科指导团队的研究目标、培训活动和指导将使 开发一项成功的独立研究计划的候选人，该计划旨在检查感觉与 减损和ADRD。目前的研究计划预计将提供对哪些因素和 机制可以解释感觉障碍和ADRD之间的联系。这些发现将告诉我们 是否可以将感觉障碍或其下游的心理社会影响作为干预的目标 以预防痴呆症，或者感觉障碍是否可以作为临床预测指标来识别 临床前阿尔茨海默病或脑血管疾病。

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.