Brain Morphology, Inflammation and Episodic Memory Profiles Among Persons Aging with HIV

项目概要/摘要 老年艾滋病毒感染者（PLHIV）现在面临着与年龄相关的神经退行性疾病的风险， 阿尔茨海默病（AD）及其前驱遗忘型轻度认知障碍（aMCI）。由于可能发生 艾滋病毒和衰老对大脑的复合影响，以及高发病率的医疗条件（例如，慢性 炎症）是AD的风险因素，PLHIV可能具有更高的神经退行性疾病风险， 如AD。识别艾滋病毒携带者和aMCI是复杂的，因为aMCI的定义特征，记忆， 功能障碍，也常见于艾滋病毒相关的神经认知障碍（HAND），这仍然是流行的， cART时代（30-50%），特别是在老年人中。为了提供早期、有针对性的干预措施， 认知障碍进展，临床医生必须能够准确区分手和 aMCI。然而，由于这种老龄化趋势是相对较新的，因此缺乏针对 解开HAND和aMCI。由于潜在的大脑变化的差异，记忆功能障碍 在HAND和aMCI的神经认知测试中有不同的表现。具体来说，手（更前-和 基于皮层下的）的特征在于回忆受损，但相对保留了对 神经认知测试，而aMCI（与内侧颞叶萎缩相关）的特征是 记忆和认知的损伤。因此，识别可能是临床上有用的神经认知标记物 区分HAND和aMCI。迄今为止，大多数艾滋病毒神经认知研究都优先关注 没有研究过认知能力。需要进行研究以评估 通过检查识别是否与神经解剖学相关， 与aMCI相关的结构。因此，F31研究项目旨在1）检查神经解剖学 回忆和识别的相关性，以及2）检查内侧颞叶的结构完整性是否与 随着将来的遗忘衰退（即，记忆和识别能力下降）。此外，本发明还 探索性分析将通过检查 外周炎症在记忆障碍和大脑完整性中的作用。该项目将利用纵向， 从CNS收集的存档神经影像学和神经心理学数据HIV抗逆转录病毒治疗效果 研究（宪章）计划。最后，F31供资机制提供的培训机会将 促进申请人的长期目标，成为一个独立的学术神经心理学家，致力于 改善临床多样化、高危人群中年龄相关神经认知功能下降的检测。

PROJECT SUMMARY/ABSTRACT Aging persons living with HIV (PLHIV) are now at risk of age-related neurodegenerative diseases such as Alzheimer’s disease (AD) and its precursor amnestic mild cognitive impairment (aMCI). Due to the potential for compounding effects of HIV and aging on the brain, as well as high rates of medical conditions (e.g., chronic inflammation) that are risk factors for AD, PLHIV are likely at higher risk for neurodegenerative diseases such as AD. Identifying PLHIV with aMCI is complicated because the defining characteristic of aMCI, memory dysfunction, is also common in HIV-associated neurocognitive disorders (HAND), which are still prevalent in the cART era (30-50%), particularly among older PLHIV. In order to provide early, targeted interventions and predict cognitive impairment progression, it is imperative that clinicians are able to accurately differentiate HAND and aMCI. However, because this aging trend is relatively recent, there is a paucity of research aimed at disentangling HAND and aMCI. Due to differences in underlying brain changes, memory dysfunction presents differently on neurocognitive testing in HAND versus aMCI. Specifically, HAND (more prefrontally- and subcortically-based) is characterized by impairment in recall but relatively preserved recognition performance on neurocognitive tests, whereas aMCI (associated with medial temporal lobe atrophy) is characterized by impairment in both recall and recognition. Therefore, recognition may be a clinically-useful neurocognitive marker to differentiate HAND and aMCI. To-date, the majority of HIV neurocognitive studies have preferentially focused on recall deficits and have not examined recognition. Research is needed to assess the clinical utility of recognition in disentangling aMCI and HAND by examining if recognition correlates with neuroanatomical structures associated with aMCI. This F31 research project therefore aims to 1) examine neuroanatomical correlates of recall and recognition, and 2) examine if structural integrity of the medial temporal lobe is associated with future amnestic decline (i.e., decline in recall and recognition performance) among older PLHIV. Additionally, exploratory analyses will probe biological mechanisms that put PLHIV at greater risk of aMCI by examining the role of peripheral inflammation in memory impairment and brain integrity. This project will utilize longitudinal, archival neuroimaging and neuropsychological data collected from the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) program. Finally, the training opportunities afforded by the F31 funding mechanism will facilitate the applicant’s long-term goal of becoming an independent academic neuropsychologist dedicated to improving detection of age-related neurocognitive decline in clinically-diverse, at-risk populations.