Functional Decline in Three Dementia Types

描述(由申请人提供)：日常生活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，了解阿尔茨海默病(AD)、血管性痴呆(VAD)和路易体痴呆(DLB)的预期功能减退率，以及这些痴呆症类型之间的差异。具体目标是：1)确定AD、VAD和DLB患者之间功能衰退的程度；2)评估痴呆症类型和功能衰退的关系是否因年龄或性别而异；以及3)确定某些痴呆症类型在特定活动减少的风险增加的程度。数据来源将是统一数据集(UDS)，该数据集由国家阿尔茨海默病协调中心自2005年以来开发和维护，包括从29个阿尔茨海默病中心(ADC)收集的数据。在这个纵向的、全国性的数据库中，每个参与者都有一次初始访问，并每年进行重新评估。已公布的诊断标准被采纳为UDS的一部分，并使用标准表格收集数据。分析样本将从以下所有UDS参与者中抽取：1)至少2次就诊，其中在就诊1(痴呆症的临床诊断和可能的AD、可能的VAD或DLB的初步诊断)符合诊断标准；2)60岁(就诊1)；3)临床痴呆症评分-盒子总和(CDR-SOB)评分16(就诊1)；以及4)连续就诊的间隔时间限制为0.5-1.5年。目前，有2846名参与者符合这些标准(2610名AD，174名DLB，62名VAD)。所有参与者2次访问，1339人3次访问，442人4次访问，10人5次访问。随着UDS继续招募新的参与者并遵循现有的参与者，这些数字将会增加。对于目标1，将检查在每次访问时测量的两个连续结果：功能活动问卷(FAQ)的总分和CDR量表的CDR-SOB分数。线性混合效应模型将被用来检验痴呆症类型对功能减退率的影响，同时考虑受试者内部和中心内结果的相关性和潜在的混杂变量(年龄、性别、种族、婚姻状况、教育程度、合并疾病、症状出现的时间、基线认知障碍)。为了评估年龄和性别在多大程度上改变痴呆症类型对功能衰退的影响(目标2)，将测试交互作用项是否包括在模型中。在目标3中，我们将检验FAQ中的四个特定活动(以及CDR中的两个相应项目)，并基于假设选择一个先验假设，即这些活动涉及已知的认知领域，相对于AD，DLB和VAD受到的损害更大。对于每项活动，将得出(过去一年)下降/不下降的二元结果，并将使用广义线性混合模型来检查下降几率与痴呆症类型之间的关联。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在日常生活活动中的帮助需求。

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.