Measuring Altered Social Behavior in Neurodegenerative Disease

描述(申请人提供)：社会行为和个性的改变通常是神经退行性疾病的首发症状，并最终发生在大多数痴呆症的过程中。然而，目前还没有工具被证实可以测量认知能力和神经心理测试耐力有限的患者的社会行为缺陷。该项目的具体目标是使现有的社会认知测量方法适用于神经退行性疾病的可靠和有效的使用。由此产生的组合将1)实施额颞叶变性的社会标准，以改进早期诊断，2)识别其他痴呆症的社会功能的特征模式，3)提供健康老年人社会功能的有效、规范的测量，4)将社会认知的定量数据与结构神经解剖学联系起来。一项为期五年的横断面调查将与325例患者(50例可能的阿尔茨海默病，50例可能的阿尔茨海默病，50例额颞叶痴呆，50例脑血管疾病，25例语义性痴呆，25例进行性非流利性失语，25例路易体痴呆，25例进行性核上性瘫痪，25例皮质基底膜变性)以及100名健康老年人作为正常对照组进行横断面调查。受试者的社会行为和认知将使用多种评估模式来衡量，例如基于问卷的告密者报告、观察性临床评级以及一般和社会认知的面对面测量，包括计算机测试。社会认知成套测验将进行验证，以确定测验的项目辨别度、内部一致性、练习效果、替代形式信度、评分员间信度和一年测验稳定性。我们将得出可靠的变化指数和老年人在每项衡量标准上的表现的标准数据集。我们还将使用聚类分析来确定非社交领域的认知缺陷，如记忆、语言等是否对电池中的任何社交测试的表现施加系统性偏差。多特征-多方法矩阵和因子分析将被用来确定测试的结构有效性，当用于健康的老年人和神经退行性疾病患者时。预测有效性将使用分类判别函数分析来确定预测每个诊断的社会缺陷模式，并通过使用基于体素的结构磁共振成像形态测量来确定特定的社会症状是否与预期的局部脑组织丢失模式相对应。由此产生的电池可供临床医生使用：1)帮助鉴别诊断痴呆症；2)根据患者的社会症状提供治疗干预、预后信息和照顾者支持；3)量化个别患者随着时间的推移社会功能的变化。研究人员可以使用这样的电池1)客观地量化社会行为变化，作为治疗试验的结果衡量标准，2)调查生物相关性(即遗传学、蛋白质组学、神经解剖学等)。3)仔细量化各种疾病组中的社会缺陷，并彻底描述每种疾病的临床表型。公共卫生相关性：该项目的主要目标是建立一套心理测量学验证的社会认知和行为测量方法，既适用于健康的老年人，也适用于神经退行性疾病患者。拥有正确的测试来识别和客观地测量社会症状将直接有助于改进对额颞叶变性谱系疾病的诊断，并将为临床医生提供一种更好地描述患者症状和测量疾病进展的手段。这一测量工具还将提供一种统一的方法，研究人员可以通过它来研究正常衰老和痴呆症的社会功能，或许可以澄清大脑-行为关系，或者在治疗试验中将社会症状改善作为一项有价值的结果衡量标准。

DESCRIPTION (provided by applicant): Changes in social behavior and personality are often the first symptoms of a neurodegenerative disorder, and eventually occur in the course of most dementias. However, no tools currently exist that have been validated to measure social behavior deficits in patients who have limited cognitive capacity and endurance for neuropsychological testing. The specific aim of this project is to adapt existing measures of social cognition for reliable and valid use in neurodegenerative diseases. The resulting battery will 1) operationalize the social criteria for frontotemporal lobar degeneration to improve early diagnosis, 2) identify characteristic patterns of social function in other dementias, 3) provide a valid, normed measure of social function in healthy older adults, 4) link quantitative data about social cognition with structural neuroanatomy. A five-year cross-sectional investigation will be performed with a cohort of 325 patients (50 Probable Alzheimer's, 50 Possible Alzheimer's, 50 frontotemporal dementia, 50 cerebrovascular disease, 25 semantic dementia, 25 progressive nonfluent aphasia, 25 dementia with Lewy-bodies, 25 progressive supranuclear palsy, and 25 corticobasal degeneration), as well as 100 healthy older controls as a normative reference group. Subjects' social behavior and cognition will be measured using multiple assessment modalities such as questionnaire- based informant reports, observational clinical ratings, and face-to-face measures of general and social cognition, including computerized testing. The social cognition battery will be validated to determine tests' item discrimination, internal consistency, practice effects, alternate form reliability, interrater reliability, and 1-year test stability. We will derive reliable change indices and a normative dataset of older adults' performance on each measure. We will also use cluster analysis to determine whether cognitive deficits in non-social domains such as memory, language, etc. exert a systematic bias upon the performance of any social test in the battery. Multitrait- multimethod matrices and factor analysis will be done to determine the construct validity of the tests when used both with healthy older adults and with neurodegenerative disease patients. Predictive validity will be tested using categorical discriminant function analysis to identify the patterns of social deficits that predict each diagnosis, and by using voxel-based morphometry of structural MRIs to determine if specific social symptoms correspond to expected patterns of regional brain tissue loss. The resulting battery could be used by clinicians 1) to aid in the differential diagnosis of dementia; 2) to provide treatment interventions, prognostic information, and caregiver support based on a patient's social symptoms; 3) to quantify changes in social function over time in individual patients. Researchers could use such a battery 1) to objectively quantify social behavior changes as an outcome measure in treatment trials, 2) to investigate the biological correlates (i.e., genetics, proteomics, neuroanatomy, etc.) of social behavior in groups of patients with neurologic conditions, 3) to carefully quantify social deficits in a variety of disease groups and thoroughly characterize each disease's clinical phenotype. PUBLIC HEALTH RELEVANCE: The primary goal of this project is to establish a psychometrically validated battery of social cognition and behavior measures that can be used with both healthy older adults and patients with neurodegenerative diseases. Having the right tests to recognize and objectively measure social symptoms will directly contribute to improved diagnosis of frontotemporal lobar degeneration-spectrum diseases, and will provide a means for clinicians to better characterize their patients' symptoms and measure disease progression. This measurement tool will also provide a unified means by which researchers can study social functioning in both normal aging and dementia, perhaps clarifying brain-behavior relationships or utilizing social symptom improvement as a valuable outcome measure in treatment trials.