Understanding the Pathway to Functional Disability in Alzheimer's disease

项目摘要/摘要 残疾在老年人中很常见，是一个主要的公共卫生问题，因为它与 降低了生活质量，提高了服务利用率。阿尔茨海默病(AD)是一种主要的 致残原因。尽管它很重要，但对它的研究相对较少。 阿尔茨海默病的功能衰退过程，或驱动个体运动轨迹的机制 日常功能下降。在发展中的背景下日常能力的丧失 退行性痴呆，如阿尔茨海默病，是一个进行性的过程。也就是说，功能能力下降 沿着一个连续体，类似于认知，反映潜在疾病的进展。一位少校 拟议研究的重点是更好地理解功能衰退的完整连续体， 特别是在残疾之前和预测残疾(定义残疾)之前的早期和微妙的问题 作为主要生活领域的依赖，如日常生活的工具性和基本活动)。 残疾的发展是众多因素之间复杂相互作用的结果。在……里面 AD，显然认知能力下降是一个主要的决定因素；这个项目的一个重点是更好地 了解特定认知障碍如何导致特定领域的缺陷 日常功能。然而，除了认知之外，可能还有大量的其他 进一步促进和帮助解释个体在比率和模式上的差异的因素 拒绝。在之前的NIA支持(AG021511)下，我们开发了一种新颖而敏感的方法 来衡量在开发之前可能出现的“功能限制”功能问题 弗兰克残疾。使用这种方法，我们已经证明了轻度认知障碍 (MCI)与正常衰老和痴呆症之间的功能限制有关。vbl.使用 一项前瞻性的纵向研究设计，本项目的目标1侧重于描述 功能正常和残疾之间的中间阶段和转折点。目标2-4寻求 要了解我们在个体功能轨迹中看到的异质性，请查看 这种可变性的潜在来源。具体地说，我们将研究神经心理学如何， 神经、精神和运动障碍会影响残疾途径。此外，我们还将 检查相关的风险因素，如一般健康状况和教育程度，如何改变 功能衰退的轨迹。对功能衰退轨迹的更好理解， 而导致个人增长率和下降模式的因素将具有重要的 临床相关性：早期诊断和预后；治疗进展和早期 执行支助服务和护理规划；以及疾病的衡量 进展和潜在的疾病调整治疗的效果。项目叙事 阿尔茨海默病(AD)是导致残疾(现实世界能力下降)的主要原因 例如管理财务或药物、驾驶等)，这直接减少了 患者及其照顾者的生活质量下降，并导致经济负担增加。 尽管它们很重要，但我们并不清楚功能问题是如何发展的 以及与阿尔茨海默病相关的进展，我们也不了解 对进展性残疾有贡献。了解残疾是如何在AD中发展的 在公共卫生、预防医学和治疗方面有广泛的应用 发展，并将对儿童的个性化护理产生重要影响 病人。

Project Summary/Abstract Disability is common in the elderly and is a major public health concern because it is associated with reduced quality of life and increased service utilization. Alzheimer's Disease (AD) is a major cause of disability. Despite its importance, relatively little research has been done to understand the course of functional decline in AD, or the mechanisms that drive individual trajectories of declines in everyday function. The loss of everyday abilities in the setting of a developing degenerative dementia such as AD is a progressive process. That is, functional abilities decline along a continuum, similar to cognition, reflecting progression of the underlying disease. A major emphasis of the proposed study is to better understand the full continuum of functional decline, particularly early and subtle problems that precede and predict disability (disability being defined as dependency in major life domains such as instrumental and basic activities of daily living). The development of disability results from a complex interplay between numerous factors. In AD, clearly cognitive decline is a major determinant; a focus of this project is to better understand how specific cognitive impairments contribute to deficits in specific domains of everyday function. In addition to cognition, however, there are likely a large number of other factors that further contribute to and help explain individual variability in rates and patterns of decline. With previous NIA support (AG021511) we developed a novel and sensitive approach to measuring `functional limitations'  functional problems that likely precede the development of frank disability. Using this approach we have demonstrated that Mild Cognitive Impairment (MCI) is associated with functional limitations intermediate to normal aging and dementia. Using a prospective, longitudinal research design, Aim 1 of this project focuses on characterizing the intermediate stages and transition points between normal function and disability. Aims 2-4 seek to understand the heterogeneity we see in individual functional trajectories by examining potential sources of this variability. Specifically, we will examine how neuropsychological, neuropsychiatric, and motor impairments influence the disability pathway. In addition, we will examine how associated risk factors, such as general health status and education, modify the trajectories of functional decline. An improved understanding of trajectories of functional decline, and the factors that contribute to individual rates and patterns of decline, will have important clinical relevance for: early diagnosis and prognosis; treatment development and the early implementation of supportive services and care planning; and the measurement of disease progression and the effects of potential disease modifying treatments. Project Narrative Alzheimer's Disease (AD) is a major cause of disability (declines in real-world abilities such as manage one's finances or medications, driving, etc.), which directly reduced quality of life for patients and their caregivers, and lead to increased economic burden. Despite their importance, we do not clearly understand how functional problems develop and progress in association with AD, nor do we understand the specific factors that contribute to progressive disability. Understanding how disability develops in AD will have far reaching applications to public health, preventative medicine, and treatment development, and will also have important implications for the individualized care of patients.