Neurovascular calcification, Alzheimer’s disease and related dementias in two Native South American populations

两个南美原住民人群的神经血管钙化、阿尔茨海默病和相关痴呆症

• 批准号: 10662151
• 负责人: Andrei Irimia
• 金额: $ 245.26万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10662151
• 关键词: Affect; Age; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Atrophic; Behavior; Biological Markers; Blood; Blood Vessels; Bolivia; Brain; Brain region; Categories; Cerebrospinal Fluid; Cerebrovascular Disorders; Cognitive; Collection; Data; Diagnosis; Diagnostic; Disease; Etiology; Exposure to; Female; Head; Healthcare; High Prevalence; Impaired cognition; Industrialization; Internal carotid artery structure; Life Style; Link; Lobar; Low Prevalence; Magnetic Resonance Imaging; Manuals; Medial; Mediation; Methods; Morbidity - disease rate; Morphology; Native Americans; Neurocognitive; Pathway interactions; Persons; Population; Predictive Value; Prevalence; Preventive; Public Health; Recommendation; Resolution; Risk; South American; Stroke; Testing; Validation; Vascular Diseases; Work; X-Ray Computed Tomography; age related; aging brain; brain volume; calcification; cerebral atrophy; disorder risk; farmer; gray matter; insight; mild cognitive impairment; neuroimaging; neurovascular; novel; public health relevance; regional atrophy; risk prediction; sex; white matter

PROJECT SUMMARY Neurovascular calcification is associated with cerebrovascular disease, with mild cognitive impairment (MCI), Alzheimer’s disease and related dementias (ADRD), but mechanisms are uncertain. To clarify how calcification harms neurocognitive functions, we focus on the relationship between regional brain volume and calcification of intracranial internal carotid arteries (iICAs), which are among the blood vessels with strongest ADRD involvement. Although both medial and intimal iICACs predict disease, how iICAC relates to age-related regional brain volume trajectories, MCI, and ADRD is unknown. We propose CT studies of iICAC in two native South American populations with high iICAC prevalence: the Tsimane/Moseten people of Bolivia. These forager-farmer populations with a non-industrial lifestyle have higher iICAC prevalence than US/EU populations, but far less brain volume decline with age. Tsimane lifestyle approximates that of our preindustrial past, whereas Moseten have partial exposure to the industrialized world and are thus closer to the US/EU along the industrialization continuum. In our first aim, we will develop automated, clinician-validated methods to segment, characterize and quantify iICAC. We will (1) distinguish medial from intimal iICAC, (2) calculate iICAC volumetrics & morphology, and (3) perform validation using gold-standard manual segmentations supervised by clinicians. In our second aim, we will determine how medial vs. intimal iICAC modifies age-dependent gray matter volume trajectory. We will segment gyri/sulci from head CT at resolutions approaching that of MRI. We will relate iICAC to gyral/sulcal volumes as a function of age and sex. In our third aim, we will quantify how medial/intimal iICAC acts on regional brain volumes to influence MCI and ADRD. The extent to which medial vs. intimal iICACs are associated with regional brain atrophy that reflects MCI/ADRD will be quantified in Tsimane/Moseten (N > 1200) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI, N > 800). Establishing the relationships linking iICAC to regional atrophy and to cognitive impairment status can help to understand the etiology and pathways whereby vascular disease risk operates on the risk of MCI and ADRD through brain atrophy. This project will also inform public health strategies to recommend preventive behaviors: should blood biomarkers of disease risk predict iICAC, this would help to establish how such biomarkers associate with ADRD. Proposed approaches could augment clinicians’ diagnostic armamentarium by providing information with predictive value on cognitive trajectories leading to ADRD. This is a unique opportunity as findings may generalize to other populations. CT methods will help to further the study of brain aging and ADRD in underprivileged populations with limited access to MRI. Project findings should also help to inform the high ADRD morbidity of US Native American populations.

项目摘要 神经血管钙化与脑血管疾病、轻度认知功能障碍（MCI）有关， 阿尔茨海默病和相关痴呆症（ADRD），但机制尚不确定。为了阐明钙化 损害神经认知功能，我们专注于局部脑容量和钙化之间的关系， 颅内颈内动脉（iICA），是ADRD最强的血管之一 参与。尽管中膜和内膜iICAC都能预测疾病，但iICAC如何与年龄相关的区域性 脑容量轨迹、MCI和ADRD未知。我们建议在两个本土的南半球进行iICAC的CT研究， iICAC高患病率的美国人群：玻利维亚的Tsimane/Moseten人。这些觅食农民 非工业生活方式的人群比美国/欧盟人群的iICAC患病率更高，但远低于美国/欧盟人群。 脑容量随年龄增长而下降。Tsimane的生活方式接近我们工业化前的过去，而Moseten 部分暴露于工业化世界，因此沿着工业化更接近美国/欧盟 连续体在我们的第一个目标中，我们将开发自动化的，临床医生验证的方法来分割，表征和 量化iICAC。我们将（1）区分内侧和内膜iICAC，（2）计算iICAC体积和形态， 以及（3）使用由临床医生监督的黄金标准手动分割来执行验证。在我们的第二 目的，我们将确定内侧与内膜iICAC如何改变年龄依赖性灰质体积轨迹。我们 将以接近MRI的分辨率从头部CT分割脑回/脑沟。我们将把iICAC与脑回/脑沟联系起来 作为年龄和性别的函数。在我们的第三个目标中，我们将量化内侧/内膜iICAC如何作用于区域性 脑容量影响MCI和ADRD。中膜与内膜iICACs的相关程度 反映MCI/ADRD的局部脑萎缩将在Tsimane/Moseten（N > 1200）中定量， 阿尔茨海默病神经影像学倡议（ADNI，N > 800）。建立联系iICAC， 区域萎缩和认知障碍状态可以帮助理解病因和途径， 血管疾病风险通过脑萎缩对MCI和ADRD的风险起作用。该项目还将告知 推荐预防行为的公共卫生策略：疾病风险的血液生物标志物是否可以预测 iICAC，这将有助于确定这些生物标志物如何与ADRD相关。拟议的办法可 通过提供具有认知预测价值的信息， 导致ADRD的轨迹这是一个独特的机会，因为研究结果可能会推广到其他人群。CT 方法将有助于进一步研究脑老化和ADRD在贫困人口与有限的访问 核磁共振成像项目结果还应有助于了解美国土著居民ADRD的高发病率。