Understanding the Pathway to Functional Disability in Alzheimer's disease

了解阿尔茨海默病导致功能障碍的途径

基本信息

批准号：
8532498
负责人：
SARAH E TOMASZEWSKI-FARIAS
金额：
$ 8.95万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-01 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8532498
关键词：
Accounting Activities of Daily Living Address Affect Alzheimer&apos s Disease Area Automobile Driving Caregivers Caring Caucasians Caucasoid Race Cerebrovascular Disorders Cognition Cognitive Complex Data Dementia Dependency Development Disease Disease Progression Early Diagnosis Economic Burden Educational Background Elderly Ethnic Origin Future Goals Health Health Status Health education Heterogeneity Impaired cognition Impairment Individual Individual Differences K-Series Research Career Programs Language Lead Life Longitudinal Studies Measurement Measures Mediating Memory Minority Modeling Motor Neuropsychological Tests Pathway interactions Patient Care Patients Pattern Pharmaceutical Preparations Phase Preventive Medicine Process Public Health Quality of life Research Research Design Resources Risk Factors Role Services Source Staging Visuospatial Work clinically relevant cohort disability executive function functional decline functional disability functional outcomes improved instrument mild neurocognitive impairment motor impairment neuropsychiatry neuropsychological normal aging novel outcome forecast prospective service utilization social therapy development

项目摘要

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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.

描述（由申请人提供）：残疾在老年人中很常见，这是一个主要的公共卫生问题，因为它与生活质量降低和服务利用率的增加有关。阿尔茨海默氏病（AD）是残疾的主要原因。尽管它很重要，但对了解AD功能下降的过程或驱动单个日常功能下降的机制的研究进程相对较少。在诸如AD之类的退化性痴呆症（例如AD）的情况下，日常能力的丧失是一个渐进的过程。也就是说，沿连续体的功能能力下降，类似于认知，反映了潜在疾病的发展。拟议的研究的主要重点是更好地了解功能下降的全部连续性，尤其是在残疾之前和预测残疾之前的早期和微妙的问题（将残疾定义为主要生命领域的依赖性，例如工具和基本的日常生活活动）。残疾的发展是由于许多因素之间的复杂相互作用引起的。在AD中，显然认知能力下降是主要的决定因素。该项目的重点是更好地了解特定的认知障碍如何导致日常功能特定领域的缺陷。但是，除了认知外，还有许多其他因素进一步促成并有助于解释率和下降模式的个人变异性。在先前的NIA支持（AG021511）的情况下，我们开发了一种新颖而敏感的方法来测量“功能局限性” - 功能问题，可能是坦率的残疾发展。使用这种方法，我们证明了轻度认知障碍（MCI）与正常衰老和痴呆症的功能局限性有关。使用前瞻性的纵向研究设计，该项目的目标1着重于表征正常功能和残疾之间的中间阶段和过渡点。目标2-4试图通过检查这种变异性的潜在来源来了解我们在个别功能轨迹中看到的异质性。具体而言，我们将研究神经心理学，神经精神病学和运动障碍如何影响残疾途径。此外，我们将研究相关的风险因素（例如一般健康状况和教育）如何改变功能下降的轨迹。对功能下降的轨迹以及导致个体率和下降模式的因素的轨迹有了深刻的了解，将具有重要的临床相关性：早期诊断和预后；治疗发展以及支持服务和护理计划的早期实施；以及疾病进展的测量以及潜在的疾病修饰治疗的影响。公共卫生相关性：阿尔茨海默氏病（AD）是造成残疾的主要原因（在现实世界的能力（例如管理一个人的财务或药物，驾驶等）中下降，这直接降低了患者及其护理人员的生活质量，并导致经济负担增加。尽管它们的重要性，但我们并不清楚地了解功能问题与AD的相关性如何发展和进展，也不了解导致渐进式残疾的特定因素。了解广告中的残疾如何发展将在公共卫生，预防医学和治疗开发中涉及众多，并且对患者的个性化护理也有重要影响。