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 神经血管计算与脑血管疾病有关，具有轻度认知障碍（MCI）， 阿尔茨海默氏病和相关痴呆症（ADRD），但机制尚不确定。澄清钙化 伤害神经认知功能，我们专注于区域大脑体积与钙化之间的关系 颅内内部颈动脉（IICAS），它们是具有强大ADRD的血管之一 尽管培养基和内膜IICAC都可以预测疾病，但IICAC与年龄相关区域有何关系 大脑体积轨迹，MCI和ADRD尚不清楚。我们提出了IICAC在两个本地南部的CT研究 IICAC患病率高的美国人口：玻利维亚的Tsimane/Moseten人。这些觅食者 非工业生活方式的人口比我们/欧盟人口高的IICAC患病率更高，但要少得多 大脑体积随着年龄的增长而下降。 tsimane的生活方式近似于我们的工业前过去，而最多 部分接触工业化的世界，因此沿工业化更靠近美国/欧盟 连续。在我们的第一个目标中，我们将开发自动化的临床验证方法来细分，表征和 量化IICAC。我们将（1）与Intimal IICAC不同的培养基，（2）计算IICAC体积和形态， （3）使用临床医生监督的金标准手动分段进行验证。在我们的第二个 目的，我们将确定培养基与Intimal IICAC如何修饰与年龄相关的灰质体积轨迹。我们 将在接近MRI的分辨率下，将Gyri/sulci从头部CT进行分割。我们将将IICAC与Gyral/Sulcal联系起来 量是年龄和性别的函数。在我们的第三个目标中，我们将量化媒体/Intimal IICAC如何在地区行动 脑量会影响MCI和ADRD。媒体与Intimal IICAC与 反映MCI/ADRD的区域脑萎缩将在Tsimane/Moseten（n> 1200）中进行量化 阿尔茨海默氏病神经影像学倡议（ADNI，n> 800）。建立将IICAC与 区域萎缩和认知障碍状况可以帮助理解病因和途径 血管疾病风险操作对MCI和ADRD的风险通过脑萎缩。该项目也将告知 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应该预测 IICAC，这将有助于确定此类生物标志物如何与ADRD相关联。建议的方法可以 增强临床医生的诊断Armammentarium通过提供具有预测价值的信息 导致ADRD的轨迹。这是一个独特的机会，因为发现可能会推广到其他人群。 CT 方法将有助于进一步研究大脑衰老和ADRD的贫困人群，访问有限 到MRI。项目发现还应有助于告知美国美国原住民人口的高度发病率。