Family history of dementia and APOE e4 status predict neurocognitive trajectories among persons with HIV

项目摘要/摘要 随着高效抗逆转录病毒疗法的引入，艾滋病毒携带者(PWH)的寿命延长， 中老年威尔斯亲王比例继续上升。年龄越大，患糖尿病的风险越高。 与年龄相关的神经生殖疾病，包括阿尔茨海默病。慢性艾滋病毒和老龄化都是 与超出正常衰老预期的认知缺陷有关。合并症也增加了 年龄较大的PWH可能会增加患神经退行性疾病的风险。因此，当务之急是 重点研究PWH患者神经认知损害的预先确定的危险因素。 神经退行性疾病被认为是部分遗传的。事实上，载脂蛋白e4(Apoe E4) 等位基因会增加阿尔茨海默病等神经退行性疾病的风险，并与 神经认知结果较差。此外，有痴呆症家族史的未感染艾滋病毒(HIV-)的成年人 (FHD)被认为是痴呆症遗传标记物的替代品，患痴呆症的风险更高， 与那些没有FHD的人相比，长期的认知能力下降。我们已经证明，FHD可能是一个危险因素 与HIV相关的神经认知障碍，FHD患者的整体神经认知能力明显较差 与那些没有FHD的人相比，它的功能更好。然而，这些横截面数据并没有考虑到潜在的 FHD和APOE e4对老年人全局性和领域特异性神经认知减退率的相加效应 威尔斯亲王医院。评估FHD、APOE e4和神经认知功能下降之间的关系对于 确定老年威尔斯亲王医院易患人群的风险和神经保护因素。因此， 拟议的F31项目将跟进FHD和神经认知的初步横断面检查 顺序：1)确定一级和二级亲属的FHD和APOE e4状态是否 与中老年PWH的全局和领域特异性神经认知较差有关；2)确定 FHD和APOE e4状态是否可以预测神经认知轨迹；以及3)探讨 人口学、神经精神病学、物质使用、日常功能、合并症和艾滋病毒疾病 FHD和APOE-E4状态下的神经认知轨迹特征。拟议的研究将使用 多维成功的中老年PWH横断面和纵向档案资料 HIV感染者中的老龄化与中枢神经系统HIV抗逆转录病毒治疗效果研究项目。这个 通过F31机制提供的机会将促进申请者的职业发展 成为一名致力于促进神经认知韧性的独立学术神经心理学家 在较老的威尔斯亲王医院中。

PROJECT SUMMARY/ABSTRACT With the introduction of highly-active antiretroviral therapy, people with HIV (PWH) are living longer and the proportion of middle-older age PWH continues to rise. Advancing age is associated with an increased risk of age-related neurogenerative diseases including Alzheimer’s disease. Both chronic HIV and aging are associated with cognitive deficits beyond the expectations of normal aging. Comorbidities are also elevated in older PWH which may additionally increase risk for neurodegenerative diseases. As such, it is imperative to focus research efforts on investigating pre-determined risk factors of neurocognitive impairment among PWH. Neurodegenerative diseases are considered to be partially inherited. In fact, the apolipoprotein e4 (APOE e4) allele increases the risk of neurodegenerative diseases such as Alzheimer’s disease and is associated with poorer neurocognitive outcomes. Furthermore, HIV-uninfected (HIV-) adults with a family history of dementia (FHD), considered a proxy for genetic markers of dementia, are at a higher risk for developing dementia and long-term cognitive decline compared to those without FHD. We have shown that FHD may be a risk factor for HIV-associated neurocognitive disorders as persons with FHD have significantly worse global neurocognitive function compared to those without FHD. Nevertheless, these cross-sectional data do not address the potential additive effect of FHD and APOE e4 on rate of global and domain-specific neurocognitive decline among older PWH. Assessing the relationships between FHD, APOE e4 and neurocognitive decline is critical toward identifying risk and neuroprotective factors among the vulnerable population of older PWH. Accordingly, the proposed F31 project will follow-up on the initial cross-sectional examination of FHD and neurocognition in order to: 1) determine whether FHD among first- and second-degree relatives and APOE e4 status are associated with worse global- and domain-specific neurocognition in middle-to-older age PWH; 2) determine whether FHD and APOE e4 status predict neurocognitive trajectories; and 3) explore potential effects of demographic, neuropsychiatric, substance use, daily functioning, comorbidities, and HIV disease characteristics on neurocognitive trajectories by FHD and APOE-e4 status. The proposed research will use cross-sectional and longitudinal archival data of middle-to-older PWH from the Multi-Dimensional Successful Aging Among HIV-Infected Adults and CNS HIV Antiretroviral Therapy Effects Research programs. The opportunities afforded via this F31 mechanism will facilitate the applicant’s professional development toward becoming an independent academic neuropsychologist dedicated to promoting neurocognitive resilience among older PWH.