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: 10634706
• 负责人: Hyacinth Idu Hyacinth
• 金额: $ 120.53万
• 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/10634706
• 关键词: Adult; Alzheimer' s Disease; Alzheimer' s disease related dementia; American; Anatomy; Ancillary Study; Black Populations; Blood Vessels; Brain; Cerebral small vessel disease; Cerebrovascular system; Consensus; Dementia; Development; Disparity; District of Columbia; Epidemiology; Evaluation; Event; Genetic; Genetic Carriers; Genetic Risk; Genotype; Geography; Goals; Growth; High Prevalence; Hispanic Populations; Home; Hospitals; Hypertension; Image; Impaired cognition; Incidence; Individual; International; Lesion; MRI Scans; Magnetic Resonance Imaging; Measures; Mediator; Methodology; Minority Groups; Not Hispanic or Latino; Older Population; Participant; Pattern; Phenotype; Population; Population Heterogeneity; Prevalence; Prevention strategy; Prospective, cohort study; Race; Recovery; Reporting; Research; Resources; Retrieval; Risk; Risk Factors; Role; Severities; Stroke; Stroke Belt; TREM2 gene; Telephone; Testing; Time; Transient Ischemic Attack; US State; Variant; Vascular Cognitive Impairment; White Matter Hyperintensity; Woman; adjudication; analysis pipeline; 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; human old age (65+); 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增加(即“美国老龄化”)， 阿尔茨海默病和相关痴呆(ADRDS)的患病率。老年人比例的增加 与非西班牙裔白人相比，美国人在少数族裔人口中的发病率更高 例如，在非西班牙裔白人中，年龄最大的美国人的数量预计将增长81% 相比之下，到2030年，非西班牙裔黑人(NHBs)的增长率为131%，西班牙裔美国人的增长率为328%。 与年龄最大的美国人比例中种族差距的扩大相平行的是， ADRDS的发病率和流行率。例如，所有痴呆症的患病率要高得多 在NHBs和NHW中，NHB男性和女性的患病率是 不管是男人还是女人。在NHB男性中，阿尔茨海默氏症(AD)的患病率是 不，男人。当只检查血管性认知损害和痴呆(VCID)时，NHBs超过 即使在调整了中风累积发病率的差异后，发生VCID的可能性也是对照组的两倍 严重程度和已知的血管和痴呆症危险因素。这表明有必要确定其他可能的因素 造成了观察到的种族或黑人-白人的差异。我们的总体目标是(1)确定是否 磁共振成像(MRI)确定的CSVD标记物的患病率存在黑白差异 在ARES队列中确诊为中风/短暂性脑缺血发作的参与者中(2)确定CSVD的贡献 以及ADRD的遗传和血管风险因素导致VCID和ADRD的黑白差异。我们假设 在中风或短暂性脑缺血发作的参与者中，黑人和白人患病率和 VCI和ADRDS的发展轨迹部分是由于CSVD的患病率和负担方面的黑人和白人的差异， 可能与血管和ADRD遗传危险因素的分布差异有关。CSVD是磁共振成像 检测到以脑微出血(CMBS)、白质高信号(WMH)为成分的脑部病变 病变、腔隙和血管周围间隙扩大(EPVS)，也与血管危险因素有关 认知障碍和痴呆症的发病率和流行率。我们的假设将基于 以下目标：(1)确定慢性阻塞性肺病的患病率、模式和种族/地理差异以及 脑体积参数。(2)检查血管和遗传之间的联系(APOEε4、ABCA7和 TREM2)危险因素，以及CSVD和脑体积的患病率或差异。(3)确定关联关系 CSVD、脑体积测量与发病率、患病率、轨迹以及观察到的 黑人和白人在认知障碍和痴呆症风险方面的差异。实现上述目标将使我们能够 确定高危人群，采取更有针对性的VCID预防或治疗策略，潜在地减少 VCID中的黑白差异。此外，检索到的MRI扫描和得出的表型将是有用的 关于以下方面进一步研究的资源。

项目成果

Effect of Blood Transfusion on Cerebral Hemodynamics and Vascular Topology Described by Computational Fluid Dynamics in Sickle Cell Disease Patients.

• DOI: 10.3390/brainsci12101402
• 发表时间: 2022-10-18
• 期刊: BRAIN SCIENCES
• 影响因子: 3.3
• 作者: Sawyer, Russell P.;Pun, Sirjana;Karkoska, Kristine A.;Clendinen, Cherita A.;DeBaun, Michael R.;Gutmark, Ephraim;Barrile, Riccardo;Hyacinth, Hyacinth, I
• 通讯作者: Hyacinth, Hyacinth, I

History of obstructive sleep apnea associated with incident cognitive impairment in white but not black individuals in a US national cohort study.

在美国的一项全国队列研究中，白人（而非黑人）的阻塞性睡眠呼吸暂停史与认知障碍事件相关。

• DOI: 10.1016/j.sleep.2023.09.021
• 发表时间: 2023
• 期刊: Sleep medicine
• 影响因子: 4.8
• 作者: Sawyer,RussellP;Bennett,Aleena;Blair,Jessica;Molano,Jennifer;Timmerman,Emerlee;Foster,Forrest;Karkoska,Kristine;Hyacinth,HyacinthI;Manly,JenniferJ;Howard,VirginiaJ;Petrov,MeganE;Hoffmann,ColesM;Yu,Fang;Demel,StacieL;Aziz
• 通讯作者: Aziz

Methods of a Study to Assess the Contribution of Cerebral Small Vessel Disease and Dementia Risk Alleles to Racial Disparities in Vascular Cognitive Impairment and Dementia.

• DOI: 10.1161/jaha.123.030925
• 发表时间: 2023-09-05
• 期刊: Journal of the American Heart Association
• 影响因子: 5.4