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

老年艾滋病毒感染者的大脑形态、炎症和情景记忆特征

• 批准号: 10290302
• 负责人: Laura Michelle Campbell
• 金额: $ 3.98万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10290302
• 关键词: Acquired Immunodeficiency Syndrome; Adult; Affect; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; Archives; Atrophic; Basal Ganglia; Biological; Biological Markers; Brain; CCL2 gene; Characteristics; Chronic; Clinical; Cognition; Cognitive; Corpus striatum structure; Data; Detection; Development; Differential Diagnosis; Early Intervention; Elderly; Episodic memory; Fibrinogen; Funding Mechanisms; Future; Goals; HIV; HIV Seronegativity; HIV antiretroviral; HIV-associated neurocognitive disorder; Impaired cognition; Impairment; Inflammation; Inflammatory; Intervention; Learning; Literature; Measures; Medial; Mediating; Medical; Memory; Memory Loss; Memory impairment; Motor Skills; Nerve Degeneration; Neurocognitive; Neurocognitive Deficit; Neurodegenerative Disorders; Neuropsychology; Outcome; Performance; Peripheral; Persons; Plasma; Population; Populations at Risk; Prefrontal Cortex; Research; Research Project Grants; Retrieval; Risk; Risk Factors; Role; Sampling; Specificity; Structure; System; Temporal Lobe; age effect; age related; age related neurodegeneration; aged; amnestic mild cognitive impairment; antiretroviral therapy; base; brain morphology; forgetting; functional decline; high risk; improved; indexing; interest; memory recall; memory recognition; memory retrieval; middle age; neurobiological mechanism; neurocognitive test; neuroimaging; neurotoxic; preservation; processing speed; programs; tau Proteins; tool; training opportunity; trend

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.

项目摘要/摘要 艾滋病毒（PLHIV）的老龄化患者现在有与年龄有关的神经退行性疾病的风险 阿尔茨海默氏病（AD）及其前体赋予性轻度认知障碍（AMCI）。由于有潜力 艾滋病毒和衰老对大脑的复合作用以及高率的医疗率（例如，慢性病 炎症）是AD的危险因素，PLHIV可能患神经退行性疾病的风险更高 作为广告。用AMCI识别PLHIV很复杂，因为AMCI的定义特征，记忆 功能障碍，在与HIV相关的神经认知障碍（手）中也很常见，在 卡车擦除（30-50％），尤其是在较老的PLHIV中。为了提供早期，有针对性的干预措施并预测 认知障碍的进展，临床医生必须准确区分手，并且 AMCI。但是，由于这种衰老趋势相对较新，因此很少针对 解开手和AMCI。由于大脑的潜在变化差异，记忆功能障碍会出现 手工与AMCI的神经认知测试的不同。具体而言，手（前额叶和 基于下皮层的）的特征是召回中的损害，但在 神经认知测试，而AMCI（与培养基临时叶萎缩相关）的特征是 召回和认可的损害。因此，识别可能是临床上有用的神经认知标记 区分手和AMCI。迄今为止，大多数HIV神经认知研究优选为集中 在召回中定义，尚未检查识别。需要研究以评估 通过检查识别是否与神经解剖学相关，可以在解开AMCI和手中的识别 与AMCI相关的结构。因此，该F31研究项目的目的是1）检查神经解剖学 召回和识别的相关性，以及2）检查内侧临时叶的结构完整性是否相关 随着年龄较大的PLHIV的未来阳光下降（即召回和认可表现的下降）。此外， 探索性分析将探究生物学机制，这些机制使PLHIV通过检查AMCI的风险更大 周围炎症在记忆障碍和大脑完整性中的作用。这个项目将利用纵向， 从中枢神经系统HIV抗逆转录病毒疗法收集的档案神经影像学和神经心理学数据 研究（宪章）计划。最后，F31资助机制提供的培训机会将 促进申请人成为一名独立学术神经心理学家的长期目标 改善了与年龄相关的神经认知能力下降的检测，临床多样性，处于危险中。