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

痴呆家族史和 APOE e4 状态可预测 HIV 感染者的神经认知轨迹

• 批准号: 10327232
• 负责人: Maulika Kohli
• 金额: $ 3.9万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10327232
• 关键词: Family; history; dementia; APOE; e4; Family; history; dementia; APOE; e4

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.

项目摘要/摘要 随着引入高度活跃的抗逆转录病毒疗法，艾滋病毒（PWH）的人的寿命更长， 促进年龄与中等年龄PWH的风险增加有关。 与年龄相关的神经发生疾病，包括阿尔茨海默氏病。慢性艾滋病毒和衰老都是 与认知相关的定义超出了正常衰老的期望。合并症也提高了 较旧的PWH可能会增加神经退行性疾病的风险。因此，必须 将研究工作重点放在研究PWH中神经认知障碍的预定危险因素上。 神经退行性疾病被认为是部分遗传的。实际上，载脂蛋白E4（APOE E4） 等位基因增加了神经退行性疾病（例如阿尔茨海默氏病）的风险，与 较差的神经认知结果。此外，患有痴呆症家族史的HIV未感染（HIV-）成年人 （FHD）被认为是痴呆遗传标志物的代理，患痴呆症的风险较高 与没有FHD的认知能力下降相比。我们已经证明FHD可能是 艾滋病毒相关的神经认知障碍作为FHD患者的全球神经认知明显较差 与没有FHD的功能相比。然而，这些横截面数据并未解决潜力 FHD和APOE E4对较老的全球和域特异性神经认知率的添加作用 PWH。评估FHD，APOE E4和神经认知能力下降之间的关系至关重要 在较老的PWH脆弱人群中确定风险和神经保护因素。因此， 拟议的F31项目将在最初对FHD和神经认知的横断面检查中进行跟进。 命令：1）确定一级和二级亲戚和APOE E4状态之间的FHD是否为 与中等年龄较大的PWH中的全球和域特异性神经认知有关； 2）确定 FHD和APOE E4状态是否预测神经认知轨迹； 3）探索潜在影响 人口统计学，神经精神病学，药物使用，日常功能，合并症和艾滋病毒疾病 FHD和APOE-E4状态对神经认知轨迹的特征。拟议的研究将使用 来自多维成功的中间人PWH的横截面和纵向档案数据 HIV感染的成年人和中枢神经系统HIV抗逆转录病毒疗法的衰老影响研究计划。这 通过这种F31机制提供的机会将促进申请人的专业发展 成为一名致力于促进神经认知弹性的独立学术神经心理学家 在较旧的PWH中。