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

心血管和艾滋病毒/艾滋病对大脑结构/功能和认知的影响

基本信息

批准号：
8717548
负责人：
JAMES T. BECKER
金额：
$ 36.96万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-30 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8717548
关键词：
AIDS/HIV problem Acquired Immunodeficiency Syndrome Address Affect Age Aging Anatomy Area Atrophic Attention Behavior Blood flow Brain Brain imaging CD4 Lymphocyte Count Calcium Cardiovascular Abnormalities Cardiovascular Diseases Cardiovascular system Cerebrovascular Circulation Chronic Classification Clinical Clinical Data Cognition Cognitive Cognitive deficits Cohort Studies Comorbidity Coronary Cross-Sectional Studies Data Dementia Development Diffusion Diffusion Magnetic Resonance Imaging Disease Disease Marker Educational workshop Elderly Enrollment Evaluation Functional disorder Funding HIV HIV Infections HIV diagnosis Heart Highly Active Antiretroviral Therapy Image Incidence Individual Learning Life Link Longitudinal Studies Magnetic Resonance Imaging Measures Mediator of activation protein Medical Memory Microvascular Dysfunction Minor Modeling Natural History Neurobiology Neurocognitive Neuropsychological Tests Nomenclature Outcome Participant Pathway interactions Patients Performance Persons Prevalence Process RNA Relative (related person)Reporting Research Risk Rosa Schedule Series Severities Shapes Spectrum Analysis Spin Labels Staging Structure Syndrome Testing Thick Time Treatment Failure Viral Viral Load result age related base cerebral atrophy clinical care cognitive function cognitive reserve follow-up gray matter heart function interest intima media longitudinal design men men who have sex with men men&apos s group neuropsychiatry neuropsychological older patient public health relevance response screening treatment strategy white matter

项目摘要

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.

描述（由申请人提供）：超过50岁的艾滋病毒/艾滋病患者的比例升至2004年的所有病例的22.5％。我们对年龄和艾滋病毒/艾滋病相互作用的了解不足，因为年龄本身就是一个重要的预测者，因为年龄的神经认知表现越来越多，而不是在艾滋病的神经认知表现方面如此。尽管包括痴呆症在内的年龄与各种神经精神疾病之间存在已知的联系，但直到最近才对HIV疾病，衰老和神经精神疗法的可能相互作用引起了很多关注。本应用的目的是获得资金，以比较和对比与HIV/AIDS相关的大脑结构和功能异常与心血管异常的关系。随着心血管疾病的速度随着年龄的增长而增加，这些疾病的后果也是如此，包括大脑小血管中的异常，灰质体积减少，白质完整性改变以及区域大脑血流的变化。了解衰老的这些正常后果如何受HIV的影响对于临床护理，新治疗策略的发展以及了解与HIV相关的神经认知疾病的病理生理学。我们将评估340名参与多中心艾滋病队列研究（MACS）心血管疾病的男性的心血管，认知和大脑结构/功能状态。我们将利用近25年的先前临床和神经心理学数据，再加上新的CVD变量（例如冠状动脉钙，颈动脉内膜膜厚度）和MRI发现（解剖学，扩散成像，血液，血液流量和光谱），以解决一系列链接的脑结构和功能相关的关系，并与之相关，并将其功能相关性，这些变体的关系效果，这些变化良好，构建良好的关系，构建型，并依次，这些变化良好，并依次依靠互联性，并依次依靠链接性，这些变化效果，这些变化效果，这些变化良好，并构成了这些变化，并依次依靠互联性的关系。 HIV血清和HIV感染严重程度的标记。 MAC积累了证据表明医疗合并症是风险修饰符在神经病理过程的临床表达中的重要性，这可能是由于“认知储备”下降所致。我们将通过使用来自50岁至75岁的研究参与者的横断面和纵向数据来评估该模型。我们将检验以下假设：小血管疾病及其后果不仅改变了大脑的结构和功能，而且通过这样做，可以减少大脑/认知储备，从而使HIV疾病的影响早些时候表达，并且处于不太“严重”的临床阶段。如果支持该假设，它可能有可能改变我们在获得适当医疗管理的患者中对艾滋病毒疾病的治疗方法。我们建议HIV和CVD对大脑结构/功能有直接影响，并且CNS完整性是与认知功能的直接联系。 CVD本身可以通过增长来预测。我们预测，HIV感染会节省CVD和大脑结构之间的途径强度。也就是说，相对于未感染的男性，CVD对艾滋病毒感染者的影响将增强。