Cardiovascular and HIV/AIDS Effects on Brain Structure/Function and Cognition

 描述(由申请人提供)：艾滋病毒相关认知功能障碍的流行率仍然很高，非艾滋病毒相关因素现在是认知障碍和大脑结构变化的重要风险修饰物。也许与美国艾滋病毒携带者健康相关的最重要因素是老龄化。感染(及其后果)似乎改变了几乎所有器官系统的结构或功能的正常年龄轨迹。除了发生在50岁以上的人身上的“正常”合并症外，慢性感染可能会给大脑带来巨大的负担，导致认知和行为的改变。这 令人担忧的是，许多目前患有艾滋病毒的50岁的人是在1980/90年代感染的，并忍受了多年不受控制或控制不佳的病毒复制。在这五年的续展期间(AG034852)，我们将把我们目前的样本扩大到400名男性，另外还有70名男性&>60岁。他们将每两年接受两次扫描/测试，结果是350名男性至少接受了两次扫描，多达280名男性在13年内进行了四次扫描。脑成像方法将评估大脑灰质和白质的完整性以及大脑功能网络、脑束成像、代谢物、脑血流和血液完整性的完整性。 大脑屏障。我们将利用这些数据，结合15-30年前的信息 从多中心艾滋病队列研究中评估与HIV疾病认知和行为异常表达相关的因素的一般概念模型的相对优劣。我们将完成对亚临床血管疾病标记物、炎症、脑结构和老龄化背景下认知之间关系的详细纵向分析。我们将专门比较和对比HIV感染者和未感染者中的这些关系，以解决一系列相互关联的假设，这些假说可能导致艾滋病毒感染者相对于年龄匹配的对照组认知功能障碍的比率明显增加。

 DESCRIPTION (provided by applicant): The prevalence of HIV-related cognitive dysfunction remain high, and non-HIV-associated factors are now significant risk modifiers for cognitive impairment and alterations in brain structure. Perhaps most important factor related to the health of Americans with HIV disease is aging. The infection (and its consequences) appear to alter the normal age trajectories of structure or function in virtually all organ systems. In additon to the "normal" comorbidities that occur in individuals >50 years old, a chronic infection may result in significant burden to the brain, resulting in alterations in cognition and behavior. This concern is confounded by the fact that many individuals >50 years old currently alive with HIV disease were infected during the 1980/90s and endured years of uncontrolled or poorly controlled viral replication. During this five-year renewal period (AG034852), we will expand our current sample to 400 men with an additional 70 men >60 years old. They will undergo two scanning/testing sessions two years apart, resulting in a sample of 350 men with at least two scans, and as many as 280 men with four scans over 13 years. The brain imaging methodologies will assess the integrity of brain gray and white matter and the integrity of brain functional networks, tractography, metabolites, cerebral blood flow, and the integrity of the blood brain barrier. We will utilize these data, in combination with the 15-30 years of prior information from the Multicenter AIDS Cohort Study to evaluate the relative merits of a general conceptual model of the factors associated with the expression of cognitive and behavioral abnormalities in HIV Disease. We will complete detailed longitudinal analyses of the relationships between markers of subclinical vascular disease, inflammation, brain structure and cognition in the context of aging. We will specifically compare and contrast these relationships in HIV infected and uninfected men in order to address a series of linked hypotheses concerning possible mechanisms that may result in an apparent increase in the rate of cognitive dysfunction among HIV-infected individuals relative to age-matched controls.