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[2 R 01 AG 052132 -06]研究） 认知老化与阿尔茨海默病及相关痴呆（ADRD）差异的生命过程队列研究， 不同的老年人。KHANDLE是具有不同种族/民族组成的最大的生命历程队列之一， 1964年至今的前瞻性临床、生活方式和行为数据。在第1周期，我们招募了1712名年龄在65岁以上的患者 (mean年龄76岁，范围65-103; 60%女性），代表黑人、亚洲人、拉丁美洲人和白人，3次评估 波我们已经完成了两波评估，第三波将于2021年5月完成。所有波包括全面， 心理测量复杂的认知结果，心理社会措施，如歧视，压力，居住 病史，一个强大的临床协议，以评估普遍和事件轻度认知障碍（MCI）和ADRD和25% 用淀粉样蛋白PET和MRI成像对子样本进行检查。KHANDLE参与者包括一系列的生活经历; 25% 在美国以外出生的人中，63%的人的母亲文化程度≤高中，28%的人在童年时有财务问题，17%的人在童年时有财务问题。 出生于南方各州，基线时有24.8%的认知障碍。在这次竞争性的更新中，我们将研究扩展到 研究与认知轨迹、脑成像变化和基于脑捐赠的生命过程因素相关的 神经病理学的一个新的重点性别差异。我们将继续调查ADRD、MCI、血管 脑损伤变化和淀粉样蛋白PET利用周期1中的成像并在周期2中重复。我们将加强 KHANDLE招募了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。KHANDLE的独特定位是解决 在一个不同的队列中， 未来5年的ADRD发病率和认知变化（第2周期开始时平均年龄81岁）。我们的目标是：目标1： 评价生活经历、早中年健康和合并症的发展如何影响ADRD的发生率， 9年来的认知轨迹。我们将使用一个多样化的队列来评估累积暴露的时间， 解决种族/民族群体的差异。目的2：研究生命周期健康如何影响淀粉样蛋白PET和结构MRI 变化以及神经影像学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 在研究选择性生存的作用时， 竞争性血管死亡风险。目标4：为KHANDLE启动大脑捐赠计划， 在一个不同的队列神经病理学和评估的利益，同意和参与的预测。的结果 KHANDLE周期2将揭示减少ADRD和认知老化差异的机制。

项目成果

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.

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

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

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

在整个生命过程中的农村住宅和Khandle的晚期认知下降：因果推论。

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

Racial/Ethnic Disparities in Young Adulthood and Midlife Cardiovascular Risk Factors and Late-life Cognitive Domains: The Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study.

• DOI: 10.1097/wad.0000000000000436
• 发表时间: 2021-04-01
• 期刊: Alzheimer disease and associated disorders
• 影响因子: 2.1
• 作者: Peterson RL;George KM;Gilsanz P;Ackley S;Mayeda ER;Glymour MM;Mungas DM;DeCarli C;Whitmer RA
• 通讯作者: Whitmer RA