Functional Decline in Three Dementia Types

描述（由申请人提供）：进行正常日常生活活动的能力下降是检查痴呆症病程的一个非常显著的终点。该项目旨在为研究和临床护理提供信息，以了解阿尔茨海默病（AD），血管性痴呆（VaD）和路易体痴呆（DLB）的预期功能下降率，以及这些痴呆类型之间的差异。具体目标是：1）确定AD、VaD和DLB患者的功能下降率的差异程度; 2）评估痴呆类型和功能下降的关系是否因年龄或性别而异; 3）确定某些痴呆类型的特定活动下降风险增加的程度。数据源将是统一数据集（UDS），自2005年以来由国家阿尔茨海默病协调中心开发和维护，并由29个阿尔茨海默病中心（ADC）收集的数据组成。在这个全国性的纵向数据库中，每个参与者都有一次初次访问，并每年重新评估。采用已发表的诊断标准作为UDS的一部分，并使用标准表格收集数据。分析样本将从符合以下条件的所有UDS入组者中抽取：1）至少进行了2次访视，其中访视1时符合诊断标准（痴呆症的临床诊断和可能的AD、可能的VaD或DLB的初步诊断）; 2）年龄60岁以上（第1次就诊）; 3）临床痴呆症评级-方框总和（CDR-SOB）评分<16（第1次就诊）;（4）两次访问之间的间隔时间限制在0.5-1.5年。目前，有2 846名参与者符合这些标准（2 610 AD，174 DLB，62 VaD）。所有参与者都有2次以上的访问，1339人有3次以上的访问，442人有4次以上的访问，10人有5次访问。随着UDS继续招收新的参与者并跟踪现有参与者，这些数字将增加。对于目标1，将检查每次访视时测量的两个连续结局：功能活动问卷（FAQ）的总分和CDR量表的CDR-100评分。将使用线性混合效应模型检查痴呆类型对功能下降率的影响，同时考虑结局和潜在混杂变量（年龄、性别、人种、婚姻状况、教育、合并症、自症状发作以来的时间、基线认知障碍）的受试者内和中心内相关性。为了评价年龄和性别改变痴呆类型对功能下降的影响的程度（目的2），将检验相互作用项以纳入模型。在目标3中，我们将检查FAQ中的四个特定活动（以及CDR中的两个相应项目），这些活动涉及已知相对于AD在DLB和VaD中受损更严重的认知领域。对于每项活动，将推导出下降/无下降（过去一年）的二元结果，并将使用广义线性混合模型来检查下降几率与痴呆类型之间的关联。这项研究的结果可能有助于临床医生和家庭照顾者预测和计划痴呆症患者的日常生活活动的帮助。

DESCRIPTION (provided by applicant): Decline in ability to carry out normal activities of daily living is a highly salient end-point to examine the course of dementia. This project seeks to inform research and clinical care as to expected rates of functional decline in Alzheimer's disease (AD), vascular dementia (VaD) and dementia with Lewy bodies (DLB), and differences among these dementia types. The specific aims are: 1) Determine the extent to which the rate of functional decline differs among persons with AD, VaD, and DLB; 2) Evaluate whether the relationship of dementia type and functional decline varies by age or sex; and 3) Determine the extent to which certain dementia types are at increased risk for decline in specific activities. The data source will be the Uniform Data Set (UDS), developed and maintained by the National Alzheimer's Coordinating Center since 2005, and consisting of data collected from 29 Alzheimer's Disease Centers (ADCs). In this longitudinal, nation-wide database, each participant has an initial visit and is re-evaluated annually. Published diagnostic criteria were adopted as part of the UDS and data are collected using standard forms. The analytic sample will be drawn from all UDS enrollees who: 1) made at least 2 visits where diagnostic criteria were met at visit 1 (clinical diagnosis of dementia and primary diagnosis of probable AD, probable VaD, or DLB); 2) age 60+ years (visit 1); 3) Clinical Dementia Rating-Sum of Boxes (CDR-SOB) score <16 (visit 1); and 4) time between successive visits restricted to 0.5-1.5 years. Currently, there are 2846 participants meeting these criteria (2610 AD, 174 DLB, 62 VaD). All participants have 2+ visits, 1339 have 3+ visits, 442 have 4+ visits and 10 have 5 visits. These numbers will increase as the UDS continues to enroll new participants and follow existing ones. For aim 1, two continuous outcomes, measured at each visit, will be examined: a total score from the Functional Activities Questionnaire (FAQ) and the CDR-SOB score from the CDR scale. Linear mixed effects models will be used to examine the effect of dementia type on rate of functional decline while accounting for within-subject and within-center correlations in outcomes and potential confounding variables (age, sex, race, marital status, education, co-morbidities, time since symptom onset, baseline cognitive impairment). To evaluate the degree to which age and sex alter the effect of dementia type on functional decline (aim 2), interaction terms will be tested for inclusion in models. In aim 3, we will examine four specific activities from the FAQ (and two corresponding items from the CDR), selected a priori based on hypotheses that these activities involve cognitive domains known to be more impaired in DLB and VaD, relative to AD. For each activity, binary outcomes of decline/no decline (over the past year) will be derived and generalized linear mixed models will be used to examine the association between odds of decline and dementia type. The results of this study may assist clinicians and family caregivers to anticipate and plan for a demented individual's need for help with activities of daily living.