Amyloid Neuroimaging in Older HIV+ Individuals with Cognitive Impairment

描述（由申请人提供）：目前，超过75%的50岁以上的HIV+患者死于非HIV相关原因，这表明老年HIV+患者的认知障碍原因可能与老年HIV患者的认知障碍原因重叠。老年HIV+个体中HIV相关神经认知障碍（HAND）的病因尚不清楚，可能是由于HIV病毒本身，早发性神经退行性疾病，如阿尔茨海默病（AD）或微血管缺血性（小中风）相关认知障碍。基于先前的研究，我们假设了一个新的概念框架，即脑血管疾病合并症可能导致50-59岁年龄组HIV+个体的认知障碍，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）使用[18F] AV-45检测淀粉样蛋白摄取增加，这是AD的一个特征性发现，可用于确定这种特定的病理生理机制对老年HIV+个体认知障碍的贡献，并可能在2012年用于临床应用。我们建议的具体目的是：1)确定在年轻、年轻和老年HIV+个体中是否存在PET [18F] AV-45测量的大脑异常淀粉样蛋白积累，2)确定老年（50-59岁和60岁）HIV+ HAND患者中是否存在大脑异常淀粉样蛋白积累，3)确定异常淀粉样蛋白积累是否预测老年HIV+个体的执行功能下降。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，在时间上是不合适的；2)PET [18F] AV-45在老年HIV+ HAND个体中与未患HAND的老年HIV+个体相比摄取增加；3)PET [18F] AV-45摄取增加将预测老年HIV+个体的执行功能下降。其他新的AD、血管疾病和异常脂质代谢的神经影像学标志物也将被检查，以确定它们与HIV+ HAND患者PET [18F] AV-45摄取的关系，以及它们预测执行功能衰退的能力。我们的建议将是一种新型放射性药物示踪剂[18F] AV-45首次应用于老年HIV+患者（有或没有HAND）以及年龄和人口统计学匹配的HIV-个体。我们的建议将增加我们对50-59岁和60岁HIV+ HAND患者认知功能障碍发病机制的理解，后者是一个以前没有详细研究过的年龄范围。PET AV-45作为老年HIV+个体HAND的替代标记物的鉴定和验证可以用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.