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

说明(申请人提供)：2004年，50岁以上的艾滋病毒/艾滋病感染者占所有病例的比例上升到22.5%。我们对年龄和艾滋病毒/艾滋病如何相互作用缺乏了解正变得越来越成问题，尤其是在艾滋病的神经认知表现领域，因为年龄本身就是神经认知综合征的重要预测因素。尽管已知年龄与包括痴呆症在内的各种神经精神障碍之间的联系，但直到最近，人们才对艾滋病毒疾病、衰老和神经精神症状之间可能存在的相互作用给予了很大关注。这项申请的目的是获得资金，以比较和对比与艾滋病毒/艾滋病相关的脑结构和功能异常作为心血管异常的功能。随着心血管疾病的发病率随着年龄的增长而增加，这些疾病的后果也会随之增加，包括大脑中的小血管异常、灰质体积减少、白质完整性改变以及局部脑血流的变化。了解艾滋病毒如何影响这些正常的衰老后果，对于临床护理、开发新的治疗策略以及了解艾滋病毒相关神经认知障碍的病理生理都很重要。我们将评估参与多中心艾滋病队列研究(MACS)心血管分研究的340名男性的心血管、认知和脑结构/功能状况。我们将利用近25年的临床和神经心理学数据，结合新的CVD变量(例如冠状动脉钙、颈动脉内膜中层厚度)和MRI表现(解剖、扩散成像、血流和光谱学)来解决一系列与脑结构和功能异常相关的假说，以及它们与CVD变量、HIV血清状态和HIV感染严重程度的标记之间的关系。MACS正在积累证据，证明医学合并症作为神经病理过程临床表达的风险修饰物的重要性，可能是由于“认知储备”的减少。我们将使用研究参与者的横截面和纵向数据来评估这个模型，这些参与者的年龄从50岁到75岁不等。我们将测试这一假设，即小血管疾病及其后果不仅会改变大脑结构和功能，而且这样做会降低大脑/认知储备，使艾滋病毒疾病的影响更早地表现出来，并处于不那么严重的临床阶段。如果这一假设得到支持，它可能会改变我们在获得适当医疗管理的患者中治疗艾滋病毒疾病的方式。我们认为，HIV和CVD对大脑结构/功能有直接影响，中枢神经系统的完整性是认知功能的直接联系；CVD本身是通过年龄增长预测的。我们预测，艾滋病毒感染减缓了心血管疾病和脑结构之间的通路的强度。也就是说，相对于未感染艾滋病毒的男性，脑血管疾病对大脑结构/功能的影响将在感染艾滋病毒的男性中得到增强。 公共卫生相关性：在本研究中，我们将测量参加多中心艾滋病队列研究心血管分研究的340名男性(年龄50-75岁)的心脏和大脑功能。这组男性已经进行了长达25年的研究，我们将把这些旧数据与我们在这里收集的新信息结合起来，试图了解艾滋病毒/艾滋病是如何影响心脏和大脑的，以及这对记忆和认知问题的发展是否重要。

DESCRIPTION (provided by applicant): The proportion of persons living with HIV/AIDS who are over 50 rose to 22.5% of all cases in 2004. Our lack of understanding about how age and HIV/AIDS interact is becoming increasingly problematic, no more so than in the area of the neurocognitive manifestations of AIDS, since age is itself an important predictor of neurocognitive syndromes. In spite of the known links between age and various neuropsychiatric disorders including dementia, only recently has much attention has been paid to the possible interactions between HIV disease, aging and neuropsychiatric presentation. The purpose of this application is to obtain funding to compare and contrast brain structural and functional abnormalities associated with HIV/AIDS as a function of cardiovascular abnormalities. As the rate of cardiovascular disease increases with age, so too do the consequences of those disorders including abnormalities in the small vessel in the brain, decreased grey matter volume, altered white matter integrity, and changes in regional cerebral blood flow. Understanding how these normal consequences of aging are affected by HIV is important for clinical care, the development of new treatment strategies, and understanding the pathophysiology of HIV-Associated Neurocognitive Disorder. We will evaluate the cardiovascular, cognitive, and brain structure/function status of 340 men participating in the cardiovascular substudy of the Multicenter AIDS Cohort Study (MACS). We will take advantage of the nearly 25 years of prior clinical and neuropsychological data, combined with the new CVD variables (e.g., coronary calcium, carotid intima-media thickness) and MRI findings (anatomic, diffusion imaging, blood flow, and spectroscopy) to address a series of linked hypotheses concerning brain structural and functional abnormalities, and their relationship to CVD variables, HIV serostatus, and markers of the severity of the HIV infection. The MACS is accumulating evidence of the importance of medical comorbidities as risk modifiers for the clinical expression of a neuropathological process, likely due to a decrease in "cognitive reserve". We will evaluate this model by using both cross-sectional and longitudinal data from the study participants who range in age from 50 to 75 years old. We will test the hypothesis that small vessel disease and its consequences not only alter brain structure and function, but by doing so, decrease brain/cognitive reserve, allowing the effects of HIV disease to be expressed earlier, and at a less "severe" clinical stage. If this hypothesis is supported it could potentially alter the way in which we approach the treatment of HIV disease among patients with access to appropriate medical management. We propose that HIV and CVD have direct effects on brain structure/function, and that CNS integrity is the direct link to cognitive functions; CVD is itself predicted by advancing age. We predict that HIV infection moderates the strength of the pathway between CVD and brain structure. That is, the effects of CVD on brain structure/function will be augmented in the HIV-infected men relative to the uninfected men. PUBLIC HEALTH RELEVANCE: In the present study we will measure the functions of the heart and the brain in a group of 340 men (age 50-75 years old) who participate in the cardiovascular substudy of the Multicenter AIDS Cohort Study. This group of men has been in research for as long as 25 years, and we will combine those old data with the new information we will gather here to try to learn how HIV/AIDS affects the heart and the brain, and whether or not this is important for the development of problems with memory and cognition.