Amyloid Neuroimaging in Older HIV+ Individuals with Cognitive Impairment

描述(申请人提供)：现在超过75%的50岁以上的艾滋病毒携带者死于与艾滋病毒无关的原因，这表明老年艾滋病毒携带者的认知障碍的原因可能与老年艾滋病毒携带者的原因重叠。在艾滋病毒+的老年人中，艾滋病毒相关神经认知障碍(HAND)的原因尚未完全确定，可能是由于艾滋病毒本身，即阿尔茨海默病(AD)或微血管缺血(小中风)等神经退行性疾病的较早发病与认知障碍有关。基于先前的研究，我们假设了一个新的概念框架，即脑血管疾病合并发病可能导致50-59岁年龄组HIV+个体的认知障碍，而神经退行性疾病，如AD和脑血管疾病，导致60岁亚组HIV+个体认知障碍的频率增加。正电子发射断层扫描(PET)与[18F]AV-45一起检测淀粉样蛋白摄取增加，这是AD的一个特征发现，可以用来确定这种特定的病理生理机制对老年HIV+患者认知障碍的贡献，并可能在2012年投入临床使用。我们建议的具体目的是：1)确定用PET[18F]AV-45检测在年轻、年轻和老年HIV+患者中是否存在脑内异常淀粉样蛋白积聚，2)确定在手部HIV+患者(50-59岁和60岁)大脑中是否存在异常淀粉样蛋白积聚，以及3)确定淀粉样蛋白异常积聚是否可以预测老年HIV+患者的执行功能下降。我们假设1)PET[18F]AV-45将在HIV+个体中检测到，并且与年龄匹配的HIV个体相比在时间上将是不合适的，2)与没有手的老年HIV+个体相比，PET[18F]AV-45在有手的老年HIV+个体中的摄取将增加，以及3)PET[18F]AV-45摄取增加将预测老年HIV+个体的执行功能下降。还将检查AD、血管疾病和脂代谢异常的其他新的神经成像标记物与手部HIV+患者的PET[18F]AV-45摄取以及它们预测执行功能下降的能力之间的关系。我们的建议将是首次将新型放射性药物示踪剂[18F]AV-45应用于有或没有手和年龄以及人口统计匹配的艾滋病毒携带者的老年艾滋病毒携带者。我们的建议将增加我们对50-59岁和60岁HIV+手部感染者认知障碍发病机制的理解，后者的年龄范围以前没有详细研究过。在老年HIV+患者中，PET AV-45作为手部的替代标志物的识别和验证可能有助于识别有认知能力下降风险的患者，并可能确定治疗干预的细胞靶点。

DESCRIPTION (provided by applicant): More than 75% of HIV+ individuals over the age of 50 now die from non-HIV related causes, suggesting that the causes of cognitive impairment among older HIV+ individuals may overlap with those among elderly HIV- individuals. The cause of HIV-associated neurocognitive disorders (HAND) among older HIV+ individuals is not well established and could be due to the HIV virus itself, the earlier onset of neurodegenerative diseases such as Alzheimer's disease (AD) or microvascular ischemic (small stroke) associated cognitive impairment. Based upon previous studies, we hypothesize a new conceptual framework that cerebrovascular disease co-morbidity may contribute to cognitive impairment among HIV+ individuals in the 50-59 year age group and neurodegenerative conditions such as AD and cerebrovascular disease contribute to the increased frequency of cognitive impairment among HIV+ individuals in the ¿ 60 year subgroup. Positron emission tomography (PET) with [18F] AV-45 to detect increased amyloid uptake, a characteristic finding in AD, can be used to identify the contribution of this specific pathophysiological mechanism for cognitive impairment in older HIV+ individuals and is likely to be available for clinical use in 2012. The specific aimsof our proposal are: 1) to determine whether abnormal amyloid accumulation in brain as measured by PET [18F] AV-45 is present among young, younger aged, and older aged HIV+ individuals, 2) to determine whether abnormal amyloid accumulation in brain is present in older (50-59 year and ¿ 60 year old) HIV+ individuals with HAND, and 3) to determine whether abnormal amyloid accumulation predicts executive functioning decline in older HIV+ individuals. We hypothesize that 1) PET [18F] AV-45 will be detected in HIV+ individuals, and will be chronologically inappropriate compared to age-matched HIV- individuals, 2) PET [18F] AV-45 will have increased uptake in older HIV+ individuals with HAND compared to older HIV+ individuals without HAND, and 3) increased PET [18F] AV-45 uptake will predict executive functioning decline in older HIV+ individuals. Other novel neuroimaging markers of AD, vascular disease, and abnormal lipid metabolism will also be examined for their association with both PET [18F] AV-45 uptake in HIV+ individuals with HAND, and their ability to predict executive functioning decline. Our proposal will be the first application of [18F] AV-45, a novel radiopharmaceutical tracer, in older HIV+ individuals with and without HAND and age and demographically matched HIV- individuals. Our proposal will increase our understanding of pathogenetic mechanisms of cognitive impairment in both 50-59 year old and ¿ 60 year old HIV+ individuals with HAND, the latter group an age range not previously examined in detail. The identification and validation of PET AV-45 as a surrogate marker for HAND in older HIV+ individuals could serve to identify patients at risk for cognitive decline, and may identify cellular targets for therapeutic intervention.