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

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 随着老年人口比例的不断增加（即“美国的老龄化”）， 阿尔茨海默病和相关痴呆症 (ADRD) 的患病率 老年人比例增加。 与非西班牙裔白人相比，美国人中少数族裔的发生率更快 例如，非西班牙裔白人中“最年长”的美国人数量预计将增长 81% 相比之下，到 2030 年，非西班牙裔黑人 (NHB) 的增长率为 131%，西班牙裔的增长率为 328%。 与美国最年长人口比例日益扩大的种族差距相伴随的是， ADRD 的发病率和患病率 例如，所有痴呆症的患病率都显着升高。 与 NHW 相比，NHB 中的患病率是男性和女性的 2 – 2.5 倍 NHW 男性或女性中，阿尔茨海默病 (AD) 的患病率是 NHB 男性的 2.5 倍。 当仅检查血管性认知障碍和痴呆 (VCID) 时，NHW 男性的数量超过 即使在调整中风累积发病率差异后，发生 VCID 的可能性也会增加一倍 严重程度以及已知的血管和痴呆风险因素表明需要确定其他可能的因素。 我们的总体目标是（1）确定是否会加剧所观察到的种族或黑人与白人之间的差异。 磁共振成像 (MRI) 定义的 CSVD 标志物的流行率存在黑白差异 REGARDS 队列中患有确诊中风/TIA 的参与者，以及 (2) 确定 CSVD 的贡献 ADRD 遗传和血管危险因素导致 VCID 和 ADRD 中的黑白差异。 在患有中风或短暂性脑缺血发作 (TIA) 的 REGARDS 参与者中，患病率的黑白差异 VCI 和 ADRD 的发展轨迹部分是由于 CSVD 患病率和负担方面的黑人和白人差异造成的，这 MRI 可能与血管和 ADRD 遗传危险因素的分布差异有关。 检测到脑部病变，其成分包括脑微出血（CMB）、白质高信号（WMH） 病变、腔隙和血管周围间隙扩大 (ePVS)，也与血管危险因素相关 我们的假设将基于认知障碍和痴呆的发生率和患病率进行检验。 以下目标： (1) 确定 CSVD 的患病率、模式和种族/地理差异以及变异 (2) 检查血管和遗传之间的关联（APOE ε4、ABCA7 和 TREM2) 危险因素以及 CSVD 和脑容量的患病率或差异 (3) 确定关联。 CSVD、脑容量测量与发病率、患病率和轨迹以及任何观察到的 认知障碍和痴呆症风险的黑人与白人差异将使我们能够实现上述目标。 确定高危人群，采取更有针对性的 VCID 预防或治疗策略，以潜在减少 此外，检索的 MRI 扫描和导出的表型将是有用的。 REGRARDS 进一步研究的资源。