Markers of transition to Alzheimer disease in veterans with MCI

患有 MCI 的退伍军人向阿尔茨海默病转变的标志物

• 批准号: 8413425
• 负责人: Mary Sano
• 金额: --
• 依托单位: JAMES J PETERS VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-10-01 至 2015-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8413425
• 关键词: Address; Aging; Alzheimer' s Disease; Amyloid; Amyloid Proteins; Biological; Biological Markers; Blood; Blood Vessels; Brain Pathology; Caring; Caucasians; Caucasoid Race; Cerebrospinal Fluid; Clinical; Clinical Trials; Cognition; Cognitive; Cognitive deficits; Collection; Comorbidity; Complex; Cox Models; Dementia; Deposition; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Disease Management; Early Diagnosis; Early identification; Elderly; Equation; Etiology; Future; Health; Health Care Costs; Healthcare; Healthcare Systems; Human; Impaired cognition; Individual; Injury; Intervention; Knowledge; Label; Lead; Longitudinal Studies; Measures; Medical; Medical center; Memory; Memory impairment; Mental Health; Modeling; Neurofibrillary Tangles; Neurons; Neuropsychological Tests; Outcome; Outcome Measure; Participant; Pathology; Patient Care; Patients; Population; Post-Traumatic Stress Disorders; Predictive Value; Public Health; Recruitment Activity; Resources; Risk; Risk Factors; Sampling; Senile Plaques; Services; Spinal Puncture; Staging; System; Techniques; Time; Traumatic Brain Injury; Veterans; Work; apolipoprotein E-4; base; cohort; effective therapy; extracellular; functional disability; high risk; hyperphosphorylated tau; interest; mild cognitive impairment; neuropathology; neuropsychological; novel diagnostics; predictive modeling; success; tau Proteins; tau aggregation; tau-1; therapeutic development; treatment strategy

DESCRIPTION (provided by applicant): Many studies demonstrate that memory deficit and cerebrospinal fluid markers of amyloid and tau are predictive of incident dementia. These markers have even been proposed as new diagnostic criteria for Alzheimer's disease and as outcome measures in clinical trials. Yet these studies have largely been conducted in homogeneous samples of healthy, well educated, Caucasian elders. There is no information on the value of these markers in more typical aging populations representing the broad demographic spectrum who often have multiple comorbidities. Given the aging veteran population, and their increasing need for health care, it is critical to develop accurate diagnostic and predictive models of disease, in order to target treatment and disease management. This application proposes to conduct a longitudinal study of aging veterans to determine if specific neuropsychological and CSF markers can predict transition to Alzheimer dementia and the rate of cognitive, functional and global decline. 150 veteran participants with new onset cognitive complaint will undergo neuropsychological testing and lumbar puncture for the collection of CSF markers of tau and amyloid. They will be characterized by strict neuropsychological criteria as amnestic Mild Cognitive Impairment or nonmnestic Mild Cognitive Impairment. CSF markers of tau and amyloid will be used to define the "Alzheimer signature" of CSF. Key comorbidities will be assessed as covariates including Apolipoprotein E4, vascular risk factors, the presence of Post Traumatic Stress Disorder and mild Traumatic Brain Injury. Participants will be followed for up to 3 years and assessed at 6 month intervals to determine the rate of change on clinical outcomes and the transition to dementia. We hypothesize that new onset cognitive deficit in both amnestic and non-amnestic domains (i.e. aMCI and naMCI) will predict clinical decline and dementia. We also hypothesize that the CSF biomarker signature will predict clinical decline and dementia in those with cognitive deficits (MCI) regardless of the presence of memory deficit. Cumulative transition rates will be estimated based on the survival curves generated from the Cox models. Rates of cognitive, functional and clinical decline will be compared between amnestic and non amnestic groups and between CSF signature positive and signature negative groups using the generalized estimating equation technique. Additional analyses will compare these markers alone and in combination to determine the best predictor model for dementia in this cohort. These results offer the opportunity to evaluate these markers in a high risk population of veterans who have complex medical needs. It will address the question of which tests and diagnostic approaches have the greatest value in predicting Alzheimer disease and clinical decline.

描述（由申请人提供）： 许多研究表明，记忆缺陷以及脑脊液中淀粉样蛋白和 tau 蛋白标记物可以预测痴呆的发生。这些标志物甚至被提议作为阿尔​​茨海默病的新诊断标准和临床试验的结果衡量标准。然而，这些研究主要是在健康、受过良好教育的白人老年人的同质样本中进行的。目前还没有关于这些标志物在代表广泛人口谱（通常患有多种合并症）的更典型老龄化人群中的价值的信息。鉴于退伍军人人口老龄化以及他们对医疗保健的需求不断增加，开发准确的疾病诊断和预测模型至关重要，以便有针对性的治疗和疾病管理。该申请拟对老年退伍军人进行一项纵向研究，以确定特定的神经心理学和脑脊液标记是否可以预测向阿尔茨海默氏痴呆的转变以及认知、功能和整体下降的速度。 150 名新发认知障碍的退伍军人参与者将接受神经心理学测试和腰椎穿刺，以收集脑脊液中 tau 蛋白和淀粉样蛋白标记物。它们将以严格的神经心理学标准为特征，称为遗忘性轻度认知障碍或非记忆性轻度认知障碍。脑脊液中 tau 蛋白和淀粉样蛋白标记物将用于定义脑脊液的“阿尔茨海默病特征”。关键合并症将作为协变量进行评估，包括载脂蛋白 E4、血管危险因素、创伤后应激障碍和轻度创伤性脑损伤的存在。参与者将被跟踪长达 3 年，并每隔 6 个月进行一次评估，以确定临床结果的变化率和向痴呆症的转变。我们假设遗忘和非遗忘领域（即 aMCI 和 naMCI）中新发生的认知缺陷将预测临床衰退和痴呆。我们还假设，无论是否存在记忆缺陷，脑脊液生物标志物特征都可以预测认知缺陷（MCI）患者的临床衰退和痴呆。累积转变率将根据 Cox 模型生成的生存曲线进行估计。将使用广义估计方程技术比较遗忘组和非遗忘组之间以及脑脊液特征阳性组和特征阴性组之间的认知、功能和临床下降率。其他分析将单独或组合比较这些标志物，以确定该队列中痴呆症的最佳预测模型。这些结果提供了在具有复杂医疗需求的高风险退伍军人群体中评估这些标记物的机会。它将解决哪些测试和诊断方法在预测阿尔茨海默病和临床衰退方面最有价值的问题。