Cerebral small vessel disease burden and racial disparity in vascular cognitive impairment and Alzheimer’s disease and its related dementias

脑小血管疾病负担以及血管性认知障碍和阿尔茨海默病及其相关痴呆的种族差异

• 批准号: 10214110
• 负责人: Hyacinth Idu Hyacinth
• 金额: $ 150.51万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10214110
• 关键词: Adult; Age; Alleles; Alzheimer' s Disease; Alzheimer' s disease related dementia; American; Americas; Anatomy; Ancillary Study; Blood Vessels; Brain; Cerebral small vessel disease; Consensus; Deltastab; Dementia; Development; District of Columbia; Epidemiology; Evaluation; Event; Genetic; Genetic Risk; Genotype; Geographic state; Geography; Goals; Growth; High Prevalence; Hispanics; Home; Hospitals; Hypertension; Image; Impaired cognition; Incidence; Individual; International; Lesion; MRI Scans; Magnetic Resonance Imaging; Measures; Mediator of activation protein; Methodology; Minority Groups; Not Hispanic or Latino; Older Population; Participant; Pattern; Phenotype; Population; Population Heterogeneity; Prevalence; Prevention strategy; Prospective cohort study; Recovery; Reporting; Research; Resources; Retrieval; Risk; Risk Factors; Role; Severities; Stroke; Stroke Belt; TREM2 gene; Telephone; Testing; Time; Transient Ischemic Attack; Variant; Vascular Cognitive Impairment; Vascular Dementia; White Matter Hyperintensity; Woman; adjudication; analysis pipeline; apolipoprotein E-4; base; black men; black women; black/white disparity; brain volume; burden of illness; carrier status; cerebral microbleeds; cognitive reserve; cognitive testing; cohort; dementia risk; design; detector; disorder risk; experience; genetic risk factor; geographic difference; gray matter; high risk population; men; neuroimaging; parent grant; post stroke; racial difference; racial disparity; risk variant; socioeconomics; stroke incidence; stroke risk; study population; treatment strategy; vascular cognitive impairment and dementia; vascular risk factor; Adult; Age; Alleles; Alzheimer' s Disease; Alzheimer' s disease related dementia; American; Americas; Anatomy; Ancillary Study; Blood Vessels; Brain; Cerebral small vessel disease; Consensus; Deltastab; Dementia; Development; District of Columbia; Epidemiology; Evaluation; Event; Genetic; Genetic Risk; Genotype; Geographic state; Geography; Goals; Growth; High Prevalence; Hispanics; Home; Hospitals; Hypertension; Image; Impaired cognition; Incidence; Individual; International; Lesion; MRI Scans; Magnetic Resonance Imaging; Measures; Mediator of activation protein; Methodology; Minority Groups; Not Hispanic or Latino; Older Population; Participant; Pattern; Phenotype; Population; Population Heterogeneity; Prevalence; Prevention strategy; Prospective cohort study; Recovery; Reporting; Research; Resources; Retrieval; Risk; Risk Factors; Role; Severities; Stroke; Stroke Belt; TREM2 gene; Telephone; Testing; Time; Transient Ischemic Attack; Variant; Vascular Cognitive Impairment; Vascular Dementia; White Matter Hyperintensity; Woman; adjudication; analysis pipeline; apolipoprotein E-4; base; black men; black women; black/white disparity; brain volume; burden of illness; carrier status; cerebral microbleeds; cognitive reserve; cognitive testing; cohort; dementia risk; design; detector; disorder risk; experience; genetic risk factor; geographic difference; gray matter; high risk population; men; neuroimaging; parent grant; post stroke; racial difference; racial disparity; risk variant; socioeconomics; stroke incidence; stroke risk; study population; treatment strategy; vascular cognitive impairment and dementia; vascular risk factor

PROJECT ABSTRACT With an increasing proportion of the population at older ages (i.e., the `graying of America'), there is a growing prevalence of Alzheimer's Disease and Related Dementias (ADRDs). The increase in proportion of older Americans is happening at a faster rate among minority populations compared with non-Hispanic Whites (NHWs), for instance, the number of “oldest” Americans is expected to grow by 81% among non-Hispanic Whites compared to 131% growth among Non-Hispanic Blacks (NHBs) and 328% among Hispanics, by the year 2030. Paralleling this increased racial disparity in the proportion of oldest Americans, is also a racial disparity in the incidence and prevalence of ADRDs. For instance, there is significantly higher prevalence of all dementias among NHBs compared to NHWs, with NHB men and women having a 2 – 2.5 times the prevalence among NHW men or women. Among NHB men, the prevalence of Alzheimer's dementia (AD) is 2.5 times that among NHW men. When only vascular cognitive impairment and dementia (VCID) is examined, NHBs were more than twice as likely to develop VCID even after adjusting for differences in cumulative incidence of stroke, stroke severity and known vascular and dementia risk factors. Suggesting the need to identify other factors that could be contributing to the observed racial or black-white disparity. Our overall goals are to (1) determine whether there is a black-white disparity in the prevalence of magnetic resonance imaging (MRI) defined markers of CSVD among participants in the REGARDS cohort with confirmed stroke/TIA and (2) identify the contributions of CSVD and ADRD genetic and vascular risk factors to the black-white disparity in VCIDs) and ADRDs. We hypothesize that among REGARDS participants who had a stroke or TIA, the black-white disparity in the prevalence and trajectory of VCI and ADRDs is partly due to black-white disparity in the prevalence and burden of CSVD, which could be related to differences in the distribution of vascular and ADRD genetic risk factors. CSVDs are MRI detected brain lesions whose components are cerebral microbleeds (CMBs), white matter hyperintensity (WMH) lesions, lacunes and enlarged perivascular spaces (ePVS) and are associated with vascular risk factors as well as incidence and prevalence of cognitive impairment and dementia. Our hypothesis will be tested based on the following aims: (1) Determine the prevalence, pattern and racial/geographic difference in CSVD and variation in brain volumetric parameters. (2) Examine the association between vascular and genetic (APOE ε4, ABCA7 and TREM2) risk factors, and prevalence or disparity in CSVD and brain volumes. (3) Determine the association between CSVD, brain volumetric measures and incidence, prevalence and trajectory as well as any observed black-white disparity in risk of cognitive impairment and dementia. Completing the above aims will enable us to identify a high-risk population for more targeted VCID prevention or treatment strategies to potentially reduce black-white disparity in VCID. Additionally, the MRI scans retrieved, and the phenotype derived will be a useful resource for further research in REGARDS.

项目摘要 随着年龄较大的人口比例越来越多（即“美国的灰色”），越来越多 阿尔茨海默氏病和相关痴呆症（ADRDS）的患病率。年龄较大的比例增加 与非西班牙裔白人相比，美国人的发生率更快 （NHWS），例如，非西班牙裔白人的“最古老”美国人的数量预计将增长81％ 到2030年，非西班牙裔黑人（NHB）的增长率为131％，西班牙裔人的增长率为328％。 在最古老的美国人比例中，这种增加的种族差异并行，也是种族差异 ADRD的发病率和患病率。例如，所有痴呆症的患病率显着较高 与NHW相比，NHB中的NHB男性和女性的患病率是2 - 2.5倍 NHW男女。在NHB男性中，阿尔茨海默氏症的痴呆症患病率（AD）是 NHW男子。当仅检查血管认知障碍和痴呆（VCID）时，NHB就超过 即使调整了中风累积事件的差异后，发展VCID的可能性是两倍 严重性和已知的血管和痴呆症风险因素。建议需要确定其他可能的因素 有助于观察到的种族或黑白差异。我们的总体目标是（1）确定是否 磁共振成像（MRI）定义的CSVD标记物的患病率存在​​黑白差异 在与确认的中风/TIA的参与者中，（2）确定CSVD的贡献 VCID和ADRD的黑白差异的ADRD遗传和血管危险因素。我们假设 在遇到中风或TIA的参与者中，患病率的黑白差异 VCI和ADRD的轨迹部分是由于CSVD的患病率和伯恩的黑白差异 可能与血管和ADRD遗传危险因素的分布差异有关。 CSVD是MRI 检测到的脑病变，其成分是脑微孔（CMB），白质超强度（WMH） 病变，lacusnes和血管周间空间（EPV）也与血管危险因素有关 作为认知障碍和痴呆症的事件和患病率。我们的假设将根据 以下目的：（1）确定CSVD的患病率，模式和种族/地理差异和变化 脑容量参数。 （2）检查血管与遗传之间的关联（ApoEε4，ABCA7和 TREM2）危险因素，CSVD和大脑体积的患病率或差异。 （3）确定关联 在CSVD，脑容量测量和入射，患病率和轨迹之间以及任何观察到的 认知障碍和痴呆症风险的黑白差异。完成上述目标将使我们能够 确定一个高风险人群，以实现更有针对性的VCID预防或治疗策略，以减少 VCID中的黑白差异。此外，还检索了MRI扫描，并且得出的表型将是有用的 用于进一步研究的资源。