Wisconsin Registry for Alzheimer's Prevention

项目总结 威斯康星州阿尔茨海默病预防登记处(WRAP)是一项纵向研究，遵循一项风险丰富的研究 从中后期到老年的队列，重点是(1)定义临床前窗口 个体，包括阿尔茨海默病(AD)的发病、蛋白质病和认知功能下降 临床症状；(2)全面了解不可改变的遗传和可改变的遗传的影响 健康和生活方式因素对认知和AD生物标记物起点和轨迹的影响；(3)表征 与认知能力下降有关的其他疾病的存在和影响--主要是血管疾病。包装 由超过1,729名(1386名活跃)中年登记的成年人组成(基线平均年龄54岁)，跟踪调查 两年一次，到目前为止平均随访12年，我们对他们进行认知、生活方式、实验室、 AD及相关疾病的医学和生物标记物评估(ADRD)。在前一个周期中，我们：(I)开发了 利用每个参与者自己的基线表现来识别细微认知衰退的方法，从而 在减少诊断偏差的同时提高对下降的敏感度；(Ii)从淀粉样蛋白获得时间信息 正电子发射断层扫描(PET)和血浆分析显示淀粉样蛋白的起始年龄可以被估计和 发现当淀粉样蛋白和tau蛋白病变存在时，认知能力下降。 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的病理/风险和血管变化/风险的各个方面独立 并共同影响大脑健康和认知能力下降；(Vi)在几个多队列中包括WRAP数据 推动这一领域向前发展的合作。有了这些收益和新的支持性初步数据，WRAP是 独特的定位，可解决下一个周期的以下主要目标和知识差距：目标1将衍生 临床前窗口的个人水平估计，定义为AD蛋白病发病和 认知衰退的开始。我们将进行3000次主要总结研究访问，从中我们将确定 认知能力下降。我们将分析4,400个现有的和2,640个预期的血浆样本，以检测与AD相关的生物标志物。 亚群接受AD(PET和/或CSF)和血管(MRI和超声)生物标记物。PET-血浆 将建立一致性，并将使用血浆衍生的ADRD生物标记物进行分析 整个队列。目标2检查关键的遗传和健康/生活方式预测因素与认知之间的关系 在AD生物标志物的背景下下降。目的3研究脑血管健康之间的相互关系 频谱及其与阿尔茨海默病相关的认知功能下降的关系。总体而言，这些问题 WRAP正在解决其纵向评估问题，高级时间建模是创新和至关重要的 涉及在个人层面上更精确地定义临床前AD，并确定 修改此窗口的因素。

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.