Lifecourse health, cerebral pathology and ethnic disparities in dementia (KHANDLE Study)

凯撒健康老龄化与多元化生活体验研究[2R01AG052132-06]于2017年启动，研究内容如下 一项关于认知老化与阿尔茨海默病和相关痴呆(ADRD)差异的生命周期队列研究 不同的老年人。Khandle是最大的生命周期队列之一，具有不同的种族/民族组成和 从1964年至今的前瞻性临床、生活方式和行为数据。在第一周期中，我们招募了1712名65岁以上的人 (平均年龄76岁，范围65-103；60%女性)，代表黑人、亚洲人、拉丁裔和白人，3评估 海浪。我们已经完成了两次评估，第三次评估将于2021年5月结束。所有的浪潮都包括全面、 心理测量复杂的认知结果，心理社会测量，如歧视，压力，居住 病史，评估流行的和偶发的轻度认知损害(MCI)和ADRD的可靠临床方案和25% 用淀粉样蛋白正电子发射计算机断层扫描和磁共振成像。Khandle参与者包含了一系列的生活经历；25% 出生在美国以外的人中，63%的母亲受过≤高中教育，28%的人报告童年时有经济问题，17%的人报告说 出生在南部各州，基线时有24.8%的认知障碍。在这次竞争性更新中，我们将我们的研究扩展到 调查与认知轨迹、脑成像变化和脑捐赠相关的生命周期因素 神经病理学，对性别差异有新的关注。我们将继续调查ADRD事件、MCI事件、血管事件 脑损伤变化和淀粉样蛋白PET在周期1中利用成像优势并在周期2中重复。我们将增强 Khandle招募了500名来自不同背景的新员工，并将调查性别差异 利用回顾数据来解释选择性生存。KHANDLE的独特定位是解决 生命周期暴露与认知和脑病理老化谱在不同队列中的增加 ADRD发生率和未来5年的认知变化(第2周期开始时的平均年龄为81岁)。我们的目标是：目标1： 评估生活经历、中年早期健康和合并症的发展如何影响ADRD的发病率和 九年来的认知轨迹。我们将使用不同的队列来评估累积暴露的时间，并将 解决种族/民族差异。目标2：检查生命周期健康对淀粉样蛋白PET和结构磁共振成像的影响 神经成像生物标记物的变化以及如何预测不同老年人的认知能力下降。目标3：调查性别差异 在不同的队列中ADRD的发生率和认知能力下降，同时研究选择性生存和 血管死亡的风险相互竞争。目标4：为KhandLe启动脑捐赠计划，描述频谱 在不同的队列中研究神经病理学，并评估兴趣、同意和参与的预测因素。调查结果来自 Khandle周期2将揭示减少ADRD和认知老化差异的机制。

The KHANDLE (Kaiser Healthy Aging and Diverse Life Experiences [2R01AG052132-06] Study initiated in 2017 is a lifecourse cohort study of disparities in cognitive ageing and Alzheimer's disease and related dementias (ADRD) in diverse elderly individuals. KHANDLE is one of the largest lifecourse cohorts with diverse racial/ethnic composition and prospective clinical, lifestyle, and behavioral data from 1964 -present. In Cycle 1, we enrolled 1712 individuals aged 65+ (mean age 76, range 65-103; 60% female) with representation of Blacks, Asians, Latinos, and Whites and 3 assessment waves. We have completed 2 assessment waves, and Wave 3 will finish May 2021. All waves include comprehensive, psychometrically sophisticated cognitive outcomes, psychosocial measures such as discrimination, stress, residential history, a robust clinical protocol to assess prevalent and incident mild cognitive impairment (MCI) and ADRD and a 25% subsample with amyloid PET and MRI imaging. KHANDLE participants encompasses an array of life experiences; 25% born outside the US, 63% with mothers ≤ high school education, 28% reporting financial problems in childhood, 17% born in Southern States, and 24.8% cognitive impairment at baseline. In this competitive renewal we extend our studies to investigate lifecourse factors related to cognitive trajectories, brain imaging changes, and brain donation based neuropathology with a new focus on sex differences. We will continue investigations of incident ADRD, MCI, vascular brain injury changes and amyloid PET taking advantage of imaging in Cycle 1 and repeating in Cycle 2. We will enhance KHANDLE with recruitment of 500 new individuals from diverse backgrounds and will investigate sex differences leveraging retrospective data to account for selective survival. KHANDLE is uniquely positioned to address timing of lifecourse exposures and the spectrum of cognitive and cerebropathological aging in a diverse cohort with increased ADRD incidence and cognitive changes in the next 5 years (mean age 81 at start of Cycle 2). Our aims are: Aim 1: Evaluate how life experiences, early- midlife health and development of comorbidities influence ADRD incidence and cognitive trajectories over 9 years. We will use a diverse cohort to evaluate timing of cumulative exposures and will address racial/ethnic group differences. Aim 2: Examine how lifecourse health impacts amyloid PET and structural MRI changes and how neuroimaging biomarkers predict cognitive decline in diverse elderly. Aim 3: Investigate sex differences in ADRD incidence and cognitive decline in a diverse cohort while investigating the role of selective survival and competing risk of vascular mortality. Aim 4: Initiate a brain donation program for KHANDLE, characterize the spectrum of neuropathology in a diverse cohort and evaluate predictors of interest, consent, and participation. Findings from KHANDLE Cycle 2 will uncover mechanisms for reducing disparities in ADRD and cognitive aging.