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

痴呆症的生命周期健康、脑病理学和种族差异（KHANDLE 研究）

• 批准号: 10666493
• 负责人: Paola Gilsanz
• 金额: $ 362.01万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10666493
• 关键词: Acceleration; Acculturation; Address; Adult; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Amyloid; Asian population; Behavioral; Biological Markers; Black Populations; Black race; Blood Vessels; Brain; Brain imaging; COVID-19 pandemic; Cerebrovascular Trauma; Cerebrum; Childhood; Clinical; Clinical Protocols; Cognitive; Cognitive aging; Cohort Studies; Community Health; Consent; Data; Data Collection; Data Linkages; Dementia; Development; Discrimination; Disparity; Education; Elderly; Enrollment; Epidemiologic Methods; Ethnic Origin; Ethnic Population; Exposure to; Face; Family member; Female; Future; Goals; Health; Heterogeneity; Image; Impaired cognition; Incidence; Individual; Infrastructure; Investigation; Latino; Latino Population; Life; Life Cycle Stages; Life Experience; Life Style; Longitudinal cohort; Magnetic Resonance Imaging; Measures; Medical; Medical Records; Mothers; Nerve Degeneration; Outcome; Outcome Study; Participant; Pathology; Phase; Population Heterogeneity; Positioning Attribute; Positron-Emission Tomography; Prevalence; Psychometrics; Public Health; Recording of previous events; Reporting; Research; Risk; Risk Reduction; Role; Security; Sex Differences; Stress; Time; United States; Visit; Woman; aged; aging brain; cardiovascular risk factor; checkup examination; childhood adversity; clinical phenotype; cognitive change; cohort; comorbidity; disparity reduction; early onset; ethnic disparity; ethnoracial; experience; health disparity; healthy aging; high risk; high school; interest; lifetime risk; men; middle age; mild cognitive impairment; mortality; neuroimaging; neuroimaging marker; neuropathology; predictive marker; programs; prospective; psychosocial; racial disparity; racial diversity; racial population; recruit; vascular injury; β-amyloid burden

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.

2017 年启动的 KHANDLE（Kaiser 健康老龄化和多样化生活体验 [2R01AG052132-06] 研究） 一项关于认知衰老和阿尔茨海默病及相关痴呆 (ADRD) 差异的生命全程队列研究 KHANDLE 是最大的生命历程群体之一，具有不同的种族/民族构成和 1964 年至今的前瞻性临床、生活方式和行为数据 在第 1 周期中，我们招募了 1712 名 65 岁以上的个体。 （平均年龄 76 岁，范围 65-103；60% 为女性），包括黑人、亚洲人、拉丁裔和白人以及 3 个评估 我们已经完成了 2 波评估，第 3 波评估将于 2021 年 5 月完成。所有波次都包括综合评估、 心理测量复杂的认知结果、社会心理测量，例如歧视、压力、居住 病史，一个强大的临床方案，用于评估普遍和偶发的轻度认知障碍 (MCI) 和 ADRD，以及 25% 淀粉样蛋白 PET 和 MRI 成像的子样本涵盖了 25% 的生活经历； 在美国境外出生，63% 的母亲≤高中学历，28% 的人在童年时期报告过经济问题，17% 出生于南部各州，基线时有 24.8% 的认知障碍。在这次竞争性更新中，我们将研究范围扩大到 研究与认知轨迹、脑成像变化和基于脑捐赠的生命历程因素 我们将继续研究 ADRD、MCI、血管事件。 脑损伤变化和淀粉样蛋白 PET 利用第 1 周期中的成像并在第 2 周期中重复。我们将加强 KHANDLE 将招募 500 名来自不同背景的新人，并将调查性别差异 利用回顾性数据来解释选择性生存问题。 不同队列中的生命全程暴露以及认知和脑病理老化的范围增加 未来 5 年 ADRD 发病率和认知变化（第 2 周期开始时的平均年龄 81 岁）我们的目标是： 目标 1： 评估生活经历、早中年健康和合并症的发展如何影响 ADRD 发生率和 我们将使用不同的队列来评估累积暴露的时间和意愿。 目标 2：研究生命全程健康如何影响淀粉样蛋白 PET 和结构 MRI。 变化以及神经影像生物标志物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。 在不同队列中研究 ADRD 发生率和认知能力下降，同时研究选择性生存和认知能力下降的作用 目标 4：启动 KHANDLE 大脑捐赠计划，描述该谱系的特征。 对不同队列中的神经病理学进行研究，并评估兴趣、同意和参与的预测因素。 KHANDLE Cycle 2 将揭示减少 ADRD 和认知衰老差异的机制。

项目成果

Lifecourse socioeconomic changes and late-life cognition in a cohort of U.S.-born and U.S. immigrants: findings from the KHANDLE study.

• DOI: 10.1186/s12889-021-10976-6
• 发表时间: 2021-05-13
• 期刊: BMC public health
• 影响因子: 4.5
• 作者: Peterson RL;George KM;Gilsanz P;Mayeda ER;Glymour MM;Meyer OL;Mungas DM;DeCarli C;Whitmer RA
• 通讯作者: Whitmer RA

Association of Early Adulthood Hypertension and Blood Pressure Change With Late-Life Neuroimaging Biomarkers.

• DOI: 10.1001/jamanetworkopen.2023.6431
• 发表时间: 2023-04-03
• 期刊: JAMA NETWORK OPEN
• 影响因子: 13.8
• 作者: George, Kristen M.;Maillard, Pauline;Gilsanz, Paola;Fletcher, Evan;Peterson, Rachel L.;Fong, Joseph;Mayeda, Elizabeth Rose;Mungas, Dan M.;Barnes, Lisa L.;Glymour, M. Maria;DeCarli, Charles;Whitmer, Rachel A.
• 通讯作者: Whitmer, Rachel A.

Rural residence across the life course and late-life cognitive decline in KHANDLE: A causal inference study.

• DOI: 10.1002/dad2.12399
• 发表时间: 2023-01
• 期刊: Alzheimer's & dementia (Amsterdam, Netherlands)

The role of nativity in heterogeneous dementia incidence in a large cohort of three Asian American groups and white older adults in California.

• DOI: 10.1002/alz.12563
• 发表时间: 2022-08
• 期刊: ALZHEIMERS & DEMENTIA
• 影响因子: 14
• 作者: Hayes-Larson, Eleanor;Fong, Joseph;Mobley, Taylor M.;Gilsanz, Paola;Whitmer, Rachel A.;Gee, Gilbert C.;Brookmeyer, Ron;Mayeda, Elizabeth Rose
• 通讯作者: Mayeda, Elizabeth Rose

Neuropathology Studies of Dementia in US Persons other than Non-Hispanic Whites.

• DOI: 10.17879/freeneuropathology-2022-3795
• 发表时间: 2022
• 期刊: JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
• 影响因子: 3.2
• 作者: Nguyen, My-le;Huie, Emily;George, Kristen;Whitmer, Rachel;Dugger, Brittany
• 通讯作者: Dugger, Brittany