CARDIOVASCULAR AND HIV/AIDS EFFECTS ON BRAIN STRUCTURE/FUNCTION AND COGNITION

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 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，这一点正变得越来越成问题，在艾滋病的神经认知表现方面也是如此，因为年龄本身就是神经认知综合征的一个重要预测因素。尽管已知年龄与包括痴呆症在内的各种神经精神疾病之间存在联系，但直到最近才对艾滋病毒/艾滋病、衰老和神经精神疾病之间可能的相互作用给予了大量关注。本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。随着年龄的增长，心血管疾病的发病率也随之增加，这些疾病的后果包括脑内小血管异常、灰质体积减少、白色物质完整性改变以及局部脑血流变化。了解这些衰老的正常后果如何受到HIV的影响，对于临床护理，开发新的治疗策略以及了解HIV相关神经认知障碍的病理生理学非常重要。我们将评估340名参与多中心艾滋病队列研究（MACS）心血管子研究的男性的心血管、认知和脑结构/功能状态。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，冠状动脉钙化、颈动脉内膜中层厚度）和MRI结果（解剖学、弥散成像、血流和光谱学），以解决一系列有关脑结构和功能异常的相关假设，以及它们与CVD变量、HIV血清状态和HIV感染严重程度标志物的关系。我们将通过使用年龄在50岁至75岁之间的研究参与者的横截面和纵向数据来评估该模型。我们认为HIV和CVD对大脑结构/功能有直接影响，CNS完整性与认知功能有直接联系; CVD本身可以通过年龄增长来预测。我们预测，HIV感染缓和心血管疾病和大脑结构之间的途径的强度。也就是说，CVD对大脑结构/功能的影响将在HIV感染的男性相对于未感染的男性中增强。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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 - it has only been recently that much attention has been paid to the possible interactions between HIV/AIDS, 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 small vessel abnormalities 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. 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 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.