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 威斯康星州阿尔茨海默氏症预防（WAP）的注册表是一项纵向研究，遵循风险增强 从中期到老年的队列，重点是（1）定义临床前窗口 在公开之前单独包括阿尔茨海默氏病（AD）蛋白质疾病和认知能力下降 临床症状； （2）全面了解不可修改遗传学和可修改的影响 关于认知和AD生物标志物的健康和生活方式因素； （3）表征 与认知下降有关的其他疾病的存在和影响 - 主体血管疾病。裹 由1,729多名（1386名活跃）成年人组成，他们参加了中年（基线平均年龄为54岁） 迄今为止，一年一年中平均进行12年的随访，我们在对其进行认知，生活方式，实验室，实验室， AD和相关疾病的医学和生物标志物评估（ADRD）。在以前的周期中我们：（i）开发 利用每个参与者自己的基线表现来识别微妙认知下降的方法，从而 提高对下降的敏感性，同时减少诊断偏见； （ii）从淀粉样蛋白得出的临时信息 正电子发射断层扫描（PET）和血浆测定法，表明可以估计淀粉样蛋白的开始年龄，并且 先前的tauopathy（iii）发现，当存在淀粉样蛋白和tau蛋白质病时，认知能力下降 加速； （iv）表明生活方式和健康因素会影响认知能力下降，并可能影响 临床前窗； （v）表明AD病理/风险和血管变化/风险独立的方面 共同影响大脑健康和认知能力下降； （vi）在几个多核心中包含包装数据 提出了该领域的协作。有了这些收益和新的支持性初步数据，包装是 独特的位置，可以解决下一个周期中以下主要目标和知识差距：AIM 1将得出 临床前窗口的人级估计值定义为AD蛋白质病和 认知能力下降的开始。我们将进行3000个主要包装研究访问，我们将从中进行表征 认知能力下降。我们将主张与广告相关的生物标志物的现有4,400个现有和2,640个预期的等离子体样本。 子集经历AD（PET和/或CSF）以及血管（MRI和超声）生物标志物。宠物 - 汗水 将建立一致性，并使用等离子衍生的ADRD生物标志物进行分析 整个队列。 AIM 2考试将关键遗传与健康/生活方式预测因素与认知之间的关系 在广告生物标志物的背景下下降。 AIM 3检查脑血管健康之间的关系 频谱及其与AD蛋白质疗法相对于认知下降的关联。总体而言，问题 Wrap正在通过其纵向评估和高级临时建模来解决，这是创新和重要的 在定义临床前广告的领域，以更高的精度在个体的水平上确定 修改此窗口的因素。