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

 描述（由申请人提供）：HIV相关认知功能障碍的患病率仍然很高，非HIV相关因素现在是认知障碍和脑结构改变的重要风险调节因素。也许与美国艾滋病患者健康相关的最重要因素是衰老。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。除了在>50岁的个体中发生的“正常”合并症之外，慢性感染可能导致大脑的显著负担，从而导致认知和行为的改变。这 令人担忧的是，目前患有HIV疾病的许多>50岁的个体在1980/90年代期间被感染，并经历了多年的不受控制或控制不良的病毒复制。在这5年的更新期（AG 034852）内，我们将把现有样本扩大至400例男性，另外增加70例年龄>60岁的男性。他们将在两年内接受两次扫描/测试，结果是350名男性至少接受两次扫描，多达280名男性在13年内接受四次扫描。脑成像方法将评估脑灰质和白色物质的完整性以及脑功能网络、纤维束成像、代谢物、脑血流和血液的完整性 脑屏障我们将利用这些数据，结合15-30年的先验信息， 从多中心艾滋病队列研究，以评估相对优点的一般概念模型的因素与表达的认知和行为异常的艾滋病毒疾病。我们将完成亚临床血管疾病，炎症，大脑结构和认知在衰老的背景下的标记物之间的关系的详细纵向分析。我们将专门比较和对比这些关系在HIV感染和未感染的男性，以解决一系列相关的假设可能的机制，可能会导致一个明显增加的认知功能障碍的艾滋病毒感染者之间的比率相对于年龄匹配的控制。

 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.