Wisconsin Registry for Alzheimer's Prevention

威斯康星州阿尔茨海默病预防登记处

• 批准号: 10655978
• 负责人: Sterling C Johnson
• 金额: $ 995.06万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10655978
• 关键词: Acceleration; Accounting; Address; Adult; Affect; Age; Age of Onset; Aging; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease related dementia; Alzheimer’s disease biomarker; Amyloid; Arterial Injury; Astrocytes; Atherosclerosis; Biological Assay; Biological Markers; Blood Vessels; Brain; Characteristics; Clinical; Cognitive; Collaborations; Data; Dementia; Diagnosis; Diagnostic; Disease; Disease Progression; Early Diagnosis; Enrollment; Funding; Genetic; Genetic Risk; Glial Fibrillary Acidic Protein; Goals; Health; Impaired cognition; Impairment; Individual; Injury; Intervention; Knowledge; Length; Life Style; Literature; Longitudinal Studies; Magnetic Resonance Imaging; Measurement; Mediating; Medical; Methods; Modeling; Nerve Degeneration; Neurons; Outcome; Participant; Performance; Persons; Phenotype; Plasma; Population; Positioning Attribute; Positron-Emission Tomography; Prognosis; Public Health; Publishing; Recording of previous events; Registries; Risk; Risk Factors; Sampling; Symptoms; Tauopathies; Techniques; Time; Vascular Cognitive Impairment; Vascular Diseases; Visit; White Matter Hyperintensity; Wisconsin; brain health; brain magnetic resonance imaging; cerebrovascular; cerebrovascular health; cognitive change; cognitive performance; cohort; follow-up; human old age (65+); improved; innovation; ischemic lesion; lifestyle factors; middle age; novel; observational cohort study; peer; pre-clinical; sex; social; tau Proteins; ultrasound

PROJECT SUMMARY The Wisconsin Registry for Alzheimer’s Prevention (WRAP) is a longitudinal study that follows a risk-enriched cohort from late-midlife into old age and focuses on (1) Defining the preclinical window at the level of the individual including the onset of Alzheimer’s disease (AD) proteinopathy and cognitive decline prior to overt clinical symptoms; (2) gaining a comprehensive picture of the effects of nonmodifiable genetics and modifiable health and lifestyle factors on cognitive and AD biomarker onsets and trajectories; (3) characterizing the presence and impact of other diseases associated with cognitive decline—chiefly vascular disease. WRAP consists of over 1,729 (1386 active) adults who enrolled in midlife (baseline mean age 54 yrs), are followed biannually for an average of 12 years of follow-up so far, and on whom we conduct cognitive, lifestyle, lab, medical and biomarker assessments of AD and related disorders (ADRD). In the prior cycle we: (i) Developed methods for identifying subtle cognitive decline utilizing each participant’s own baseline performance, thereby improving sensitivity to decline while reducing diagnostic bias; (ii) Derived temporal information from amyloid positron emission tomography (PET) and plasma assays showing that amyloid onset age can be estimated and precedes tauopathy, (iii) found that when amyloid and tau proteinopathies are present, cognitive decline accelerates; (iv) showed that lifestyle and health factors affect cognitive decline and likely impact the length of the preclinical window; (v) showed that AD pathology/risk and aspects of vascular changes/risk independently and jointly impact brain health and cognitive decline; (vi) included WRAP data in several multi-cohort collaborations that have advanced the field. With these gains and new supportive preliminary data, WRAP is uniquely positioned to address the following major aims and knowledge gaps in the next cycle: Aim 1 will derive person-level estimates of the preclinical window defined as the interval between onset of AD proteinopathy and the onset of cognitive decline. We will perform 3000 main WRAP study visits from which we will characterize cognitive decline. We will assay 4,400 existing and 2,640 anticipated plasma samples for AD-related biomarkers. Subsets undergo AD (PET and/or CSF) and vascular (MRI and ultrasound) biomarkers. PET—plasma concordances will be established, and analyses using plasma-derived ADRD biomarkers will be conducted on the entire cohort. Aim 2 examines relationships between key genetic and health/lifestyle predictors to cognitive decline in the context of AD biomarkers. Aim 3 examines the inter-relationship between cerebrovascular health spectrum and its associations with cognitive decline relative to AD proteinopathy. Overall, the questions that WRAP is addressing with its longitudinal assessments and advanced temporal modeling are innovative and vital to the field regarding defining preclinical AD with greater precision at the level of the individual, and determining the factors that modify this window.

项目摘要 威斯康星州老年痴呆症预防登记处（WRAP）是一项纵向研究， 从中年晚期到老年的队列，并侧重于（1）定义临床前窗口的水平， 包括阿尔茨海默病（AD）蛋白质病发作和认知能力下降之前， 临床症状;（2）全面了解不可改变的遗传学和可改变的遗传学的影响 健康和生活方式因素对认知和AD生物标志物发作和轨迹的影响;（3）表征 与认知能力下降相关的其他疾病的存在和影响-主要是血管疾病。包裹物 包括超过1，729名（1386名活跃的）中年成年人（基线平均年龄54岁）， 到目前为止，平均每两年进行一次随访，随访时间为12年，我们对这些人进行认知、生活方式、实验室检查， AD和相关疾病（ADRD）的医学和生物标志物评估。在上一个周期，我们：（一）制定了 利用每个参与者自己的基线表现来识别细微认知下降的方法， 提高对衰退的敏感性，同时减少诊断偏差;（ii）从淀粉样蛋白中获得时间信息 正电子发射断层扫描（PET）和血浆分析显示，可以估计淀粉样蛋白的发病年龄， 在tau蛋白病之前，（iii）发现当淀粉样蛋白和tau蛋白病存在时， 加速;（iv）表明生活方式和健康因素影响认知能力下降，并可能影响 临床前窗口;（v）显示AD病理/风险和血管变化/风险方面独立 并共同影响大脑健康和认知能力下降;（vi）将WRAP数据纳入几个多队列 这些合作推动了该领域的发展。有了这些成果和新的支持性初步数据， 在下一个周期中，具有独特的地位来解决以下主要目标和知识差距： 临床前时间窗（定义为AD蛋白质病发作和 认知能力下降的开始我们将进行3000次主要的WRAP研究访问， 认知能力下降我们将检测4，400份现有和2，640份预期血浆样本的AD相关生物标志物。 亚组接受AD（PET和/或CSF）和血管（MRI和超声）生物标志物检查。PET-血浆 将建立一致性，并使用血浆来源的ADRD生物标志物进行分析， 整个队列。目的2研究关键遗传和健康/生活方式预测因素与认知能力之间的关系。 在AD生物标志物的背景下下降。目的3探讨脑血管健康与 与AD蛋白质病相关的认知功能下降的关系。总的来说， WRAP正在解决其纵向评估和先进的时间建模是创新和至关重要的 在个体水平上更精确地定义临床前AD， 改变这个窗口的因素。