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

项目总结 神经血管钙化与脑血管疾病、轻度认知障碍(MCI)、 阿尔茨海默病和相关痴呆症(ADRD)，但机制尚不确定。为了弄清楚钙化是如何 损害神经认知功能，我们关注局部脑体积与钙化的关系。 颅内颈内动脉(IICA)，是ADRD最强的血管之一 参与其中。尽管内膜和内膜IICAC都能预测疾病，但IICAC如何与年龄相关的区域 脑容量轨迹、MCI和ADRD尚不清楚。我们建议对两个南方人的iICAC进行CT研究 IICAC患病率较高的美国人群：玻利维亚的齐曼/摩塞腾人。这些觅食的农民 非工业生活方式的人群iICAC患病率高于美国/欧盟人群，但远低于美国/欧盟人群 脑容量随着年龄的增长而下降。齐曼人的生活方式接近我们工业化前的过去，而摩西腾人 对工业化世界有部分敞口，因此在工业化过程中更接近美国/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iICAC的内侧和内膜，(2)计算iICAC的体积和形态， 以及(3)在临床医生的监督下，使用黄金标准的手动分割进行验证。在我们的第二个 目的：我们将确定内侧和内膜iICAC如何改变与年龄相关的灰质体积轨迹。我们 将以接近MRI的分辨率从头部CT分割脑回/脑沟。我们会将iICAC与脑回/脑沟联系起来 体积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iICAC对区域内膜/内膜的作用 脑容量影响MCI和ADRD。内膜与内膜IICAC之间的关联程度 反映MCI/ADRD的区域性脑萎缩将在Tsimane/Moseten(N&gt；1200)和 阿尔茨海默病神经成像倡议(ADNI，N&gt；800)。建立与廉政公署的联系 区域萎缩和认知障碍状态有助于了解其病因和途径 血管疾病风险通过脑萎缩作用于MCI和ADRD的风险。该项目还将向 建议预防行为的公共卫生策略：血液中疾病风险的生物标志物应该预测吗？ 这将有助于确定这些生物标记物与ADRD之间的关联。提议的方法可能 通过提供对认知有预测价值的信息来增强临床医生的诊断库 通往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 这些方法将有助于进一步研究贫困人口中的大脑老化和ADRD 去做核磁共振。该项目的发现也应该有助于告知美国土著美国人口中ADRD的高发病率。

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.