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

项目摘要 随着老年人口比例的增加（即，“美国的灰色化”），有一个越来越大的 阿尔茨海默病和相关痴呆症（ADRD）的患病率。老年人比例的增加 与非西班牙裔白人相比，美国人在少数民族人口中发生的速度更快 例如，在非西班牙裔白人中，“最老”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（NHB）的增长率为131%，西班牙裔为328%。 除了美国老年人比例的种族差异增加之外， ADRD的发病率和患病率。例如，所有痴呆症的患病率都要高得多， 与NHWs相比，NHB男性和女性的患病率是NHB男性和女性的2 - 2.5倍， NHW男性或女性。在NHB男性中，阿尔茨海默氏痴呆症（AD）的患病率是NHB男性的2.5倍。 NHW的人。当只检查血管性认知障碍和痴呆（VCID）时，NHB超过 即使在调整了中风累积发病率的差异后， 严重程度和已知的血管性和痴呆风险因素。这表明需要确定其他因素， 造成了明显的种族或黑白差异。我们的总体目标是（1）确定是否 磁共振成像（MRI）定义的CSVD标志物的患病率存在黑白差异 在REGARDS队列中确诊卒中/TIA的参与者中，（2）确定CSVD的贡献 和ADRD遗传和血管危险因素对VCID和ADRD中的黑白差异的影响。我们假设 在患有中风或TIA的REGARDS参与者中，患病率和 VCI和ADRD的发展轨迹部分是由于CSVD的患病率和负担的黑白差异， 可能与血管和ADRD遗传危险因素分布的差异有关。CSVD是MRI 检测到脑病变，其成分为脑微出血（CMB）、白色高信号（WMH） 病变、腔隙和血管周围间隙扩大（ePVS），也与血管风险因素相关 认知障碍和痴呆症的发病率和患病率。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/地理差异以及 脑容量参数(2)检查血管和遗传（APOE ε4，ABCA 7和 TREM 2）风险因素，以及CSVD和脑体积的患病率或差异。(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白差异。完成上述目标将使我们能够 确定高危人群，以便采取更有针对性的VCID预防或治疗策略， VCID中的黑白视差。此外，MRI扫描检索和表型推导将是有用的， 为进一步研究提供参考。

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.