EFFECTS OF ARTERIOSCLEROSIS ON BRAIN STRUCTURE AND FUNCTION

该项目涉及方案项目赠款的总体目标。我们的目标是量化 动脉硬化与脑结构和功能变化的关系，考虑到 阿尔茨海默病(AD)和脑血管疾病(CVD)病理指标。动脉硬化(AS) 与缺血、梗死和出血有众所周知的关系，并可能在发病中起作用 和AD的进展。然而，我们的初步结果表明，AS对大脑有直接影响 脑实质，因此认知，独立于梗塞和AD。我们将明确评估备选方案 动脉硬化导致脑萎缩和认知障碍的途径。具体目标1： 在尸检样本中，我们将量化大脑皮层萎缩和高管之间的关联。 功能与动脉硬化的严重程度，考虑到AD和心血管病变的严重程度。 具体目标2：在整个PPG样本中，我们将检查动脉硬化和 用替代磁共振研究皮质灰质体积和执行认知功能的纵向变化 控制AD和CVD病理的措施。具体目标3：在探索性分析中，我们将评估 血管风险状况与脑结构和功能改变的关系。具体目标4：最后， 我们将使用血管成像、神经心理学、核磁共振和神经病理学的所有四种方式来模拟 作为动脉硬化功能的AD和CVD病理改变。纵向的可用性 用重复的定量神经成像和心理测量相匹配的认知测量进行评估， 结合神经病理学数据，提供了一个独特的机会来回答关于两个主要的 公共卫生问题，AD和AS相互作用，导致脑损伤和认知障碍。

This project addresses the overarching goals of the program project grant. The objective is to quantify the association between arteriosclerosis and changes in brain structure and function, taking into account measures of Alzheimer disease (AD) and cerebrovascular disease (CVD) pathology. Arteriosclerosis (AS) has well known relationships with ischemia, infarction, and hemorrhage and may have a role in the onset and progression of AD. However, our preliminary results suggest that AS has direct effects on brain parenchyma and hence cognition, independent of infarction and AD. We will explicitly evaluate alternate pathways by which arteriosclerosis can contribute to brain atrophy and cognitive impairment. Specific aim 1: In the autopsy subsample, we will quantify the association between cerebral cortical atrophy and executive function with the severity of arteriosclerosis, taking into account the severity of AD and CVD pathology. Specific aim 2: In the entire PPG sample, we will examine the relationship between arteriosclerosis and longitudinal change in cortical gray matter volume and executive cognitive function, using surrogate MRI measures to control for AD and CVD pathology. Specific aim 3: In exploratory analyses, we will evaluate the relationship between vascular risk profile and changes in brain structure and function. Specific aim 4: Finally, we will use all four modalities of vascular imaging, neuropsychology, MRI, and neuropathology to model the changes in AD and CVD pathology as a function of arteriosclerosis. The availability of longitudinal assessment with repeated quantitative neuroimaging and psychometrically-matched measures of cognition, together with neuropathology data, presents a unique opportunity to answer questions about how two major public health problems, AD and AS interact to cause brain injury and cognitive impairment.