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

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.

项目总结/摘要 随着高效抗逆转录病毒疗法的引入，艾滋病毒感染者（PWH）的寿命延长， 中老年威尔斯亲王医院的比例持续上升。年龄增长与以下风险增加有关： 与年龄相关的神经退行性疾病，包括阿尔茨海默病。慢性艾滋病和衰老都是 与超出正常衰老预期的认知缺陷有关。合并症也增加， 这可能会增加患神经退行性疾病的风险。因此，必须 集中研究工作，调查预先确定的危险因素，神经认知功能障碍的PWH。 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） 等位基因增加神经退行性疾病如阿尔茨海默病的风险，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的代表，患痴呆症的风险更高， 长期认知能力下降的人相比，没有FHD。我们已经表明，FHD可能是一个危险因素， HIV相关的神经认知障碍与FHD患者相比， 与没有FHD的人相比。然而，这些横截面数据并没有解决潜在的 老年人中FHD和APOE e4对整体和领域特异性神经认知下降率的累加效应 PWH。评估FHD、APOE e4和神经认知功能下降之间的关系对于 在年老威尔斯亲王医院的弱势人口中找出风险和神经保护因素。因此 拟议中的F31项目将对FHD和神经认知的初步横断面检查进行随访， 为了：1）确定一级和二级亲属中的FHD和APOE e4状态是否 与中老年PWH中更差的全局和领域特异性神经认知相关; 2）确定 FHD和APOE e4状态是否可预测神经认知轨迹;以及3）探索 人口统计学、神经精神病学、物质使用、日常功能、合并症和HIV疾病 FHD和APOE-e4状态对神经认知轨迹的影响。该研究将使用 中老年PWH的横截面和纵向档案数据来自多维成功 HIV感染成人的衰老和CNS HIV抗逆转录病毒治疗效果研究项目。的 通过这种F31机制提供的机会将促进申请人的专业发展， 成为一名独立的学术神经心理学家，致力于促进神经认知弹性 在老年威尔斯亲王医院。