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

项目摘要/摘要 老年艾滋病毒携带者(PLHIV)现在面临与年龄有关的神经退行性疾病的风险，如 阿尔茨海默病(AD)及其前驱遗忘性轻度认知障碍(AMCI)。由于潜在的 艾滋病毒和衰老对大脑的复合影响，以及高比率的医疗条件(例如，慢性 炎症)是AD的危险因素，PLHIV可能有更高的神经退行性疾病风险，如 作为AD。识别PLHIV与aMCI是复杂的，因为aMCI的定义特征是记忆 功能障碍在HIV相关的神经认知障碍(HAND)中也很常见，这种疾病仍然流行于 Cart Era(30%-50%)，特别是在老年PLHIV中。为了提供早期、有针对性的干预和预测 认知功能障碍的进展，临床医生必须能够准确地区分手和 AMCI。然而，由于这种老龄化趋势是相对较新的，针对以下方面的研究很少 解开手和AMCI。由于潜在的大脑变化的不同，记忆障碍呈现 在手部神经认知测试和aMCI上的不同。具体地说，手(更前额-和 基于亚皮质的)的特征是回忆能力受损，但在 神经认知测试，而aMCI(与内侧颞叶萎缩有关)的特征是 在回忆和再认方面都有障碍。因此，再认可能是临床上有用的神经认知标记物。 以辨别Hand和AMCI。到目前为止，大多数的艾滋病毒神经认知研究优先集中在 关于回忆缺陷，并没有审查认可。需要研究来评估这种药物的临床效用。 通过检测识别是否与神经解剖学相关来解开AMCI和手的识别 与aMCI关联的结构。因此，该F31研究项目旨在1)检查神经解剖学 回忆和再认的相关性，以及2)检查内侧颞叶的结构完整性是否相关 在老年人中，未来遗忘性下降(即回忆和再认成绩的下降)。另外， 探索性分析将探索使PLHIV处于更大的急性心肌梗死风险的生物机制，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， 神经影像和神经心理学资料收集自中枢神经系统HIV抗逆转录病毒治疗的效果 研究(特许)计划。最后，F31资助机制提供的培训机会将 促进申请者成为一名独立的学术神经心理学家的长期目标 改进对临床多样化的高危人群中与年龄相关的神经认知下降的检测。

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.