Epidemiology of Age-related Dementia, Mild Cognitive Impairment and Brain Pathology in a Multiethnic Cohort of Oldest-Old

项目摘要 90后生活研究是一项针对阿尔茨海默病和相关痴呆症（ADRD）的生命过程队列研究， 老年病理学和认知老化在不同的老年人。最近推出，并仍在招募，LA 90是 一项最大、最具种族/种族多样性的高龄老人队列研究，前瞻性临床和生活方式数据来自 1960/70年代在第1周期中，我们招募了908名年龄在90岁以上（平均年龄92.6岁，范围90-105岁）的患者，他们来自一系列的胸腔镜检查。 背景（22%黑人，24%亚裔，20%拉丁裔，28%白色，1%其他，6%多种族）。参与者每6 迄今为止，平均每人进行了2.9次研究访问。所有的访问都包括一个广泛的神经心理学电池 和临床考试，研究访谈，包括生命过程社会经验的措施，大脑捐赠计划，以及， 包括PET和MRI成像。LA 90队列包含一系列生活经历，17%出生于 在美国以外，35%的人受过高中教育，40%的人会多种语言或将英语作为第二语言， 24%出生在美国南部。我们的初步研究结果表明，有巨大的异质性和复杂性的轨迹， 认知变化、大脑病理学和大脑状态的神经影像学标记物在10岁和11岁的生活中。在这 竞争性更新申请，我们扩展我们的科学研究血液为基础的生物标志物ADRD在最古老的老 使用ATN框架（淀粉样蛋白，tau蛋白，神经变性），扩展我们基于大脑捐赠的病理学，并招募一名 500多名不同民族/种族的参与者。此外，我们将利用数十年的前期健康数据， 可用于识别最年长的认知“超级阿格”的早期和中年标记。我们的目标是：目标1。注册500人 额外的最年长的个体，以确定更精确的年龄特异性，种族特异性和性别特异性的发病率， 认知功能障碍、ADRD和认知能力下降超过8年。目的2：确定神经影像学的贡献 淀粉样蛋白、血管损伤和脑萎缩的标志物对不同高龄老人认知能力下降和ADRD的影响。目标3： 继续入组大脑捐赠，并描述大脑病理对认知能力下降的贡献，以及 最老的老人中的ADRD。目的4：收集和量化与ATN框架一致的血液生物标志物， 评估其对不同高龄老人的ADRD和认知障碍的贡献。目标5：在多样化的 年龄最大的老年人队列，识别和理解认知“超级阿格”的生命过程预测因子。LA 90的更新将创建 一个前所未有的科学资源，用于研究ADRD和认知结果在一个不同的队列最古老的老年人 个体，一个代表这个群体迅速多样化的群体。

Project Summary The Life After 90 Study is a lifecourse cohort study of Alzheimer's disease and related dementia (ADRD), cerebropathology, and cognitive aging in diverse oldest-old individuals. Recently launched, and still enrolling, LA90 is the largest, most ethnic/racially diverse cohort study of the oldest-old with prospective clinical and lifestyle data from as early as 1960/70s. In Cycle 1, we enrolled 908 individuals aged 90+ (mean age 92.6, range 90-105) from a range of enthoracial backgrounds (22% Black, 24% Asian, 20% Latino, 28% White, 1% Other, 6% Multi-Race). Participants are seen every 6 months with an average of 2.9 research visits per person to date. All visits include an extensive neuropsychology battery and clinical exam, research interview including measures of lifecourse social experience, brain donation program, and, among a subset, PET and MRI imaging. The LA90 cohort encompasses an array of life experiences, 17% were born outside of the US, 35% have <high school education, 40% are multilingual or learned English as a second language, and 24% born in southern US. Our initial findings suggest that there is vast heterogeneity and complexity in the trajectory of cognitive change, brain pathologies, and neuroimaging markers of brain status in the 10th and 11th decade of life. In this competitive renewal application, we extend our science to investigate blood-based biomarkers for ADRD in oldest-old using the ATN framework (amyloid, tau, neurodegeneration), expand our brain donation-based pathology, and enroll an additional 500 ethnic/racially diverse participants. Additionally, we will leverage decades of antecedent health data available to identify early and midlife markers for oldest-old cognitive `SuperAgers'. Our aims are: Aim 1. Enroll 500 additional oldest-old individuals to determine more precise age-specific, race-specific, and sex- specific incident rates of cognitive impairment, ADRD, and cognitive decline over 8 years. Aim 2: Determine the contribution of neuroimaging markers of amyloid, vascular injury, and brain atrophy on cognitive decline and ADRD in diverse oldest-old. Aim 3: Continue enrollment into brain donation and characterize the contribution of brain pathologies on cognitive decline, and ADRD in the oldest-old. Aim 4: Collect and quantify blood-based biomarkers consistent with the ATN framework and evaluate their contribution to ADRD and cognitive impairment in diverse oldest-old individuals. Aim 5: In a diverse cohort of oldest-old, identify and understand lifecourse predictors of cognitive `SuperAgers'. Renewal of LA90 will create an unprecedented scientific resource for studying ADRD and cognitive outcomes in a diverse cohort of oldest-old individuals, a group representing the rapid diversification of this population.