Neural Correlates of Working Memory Training For HIV Patients

HIV 患者工作记忆训练的神经相关性

• 批准号: 9493185
• 负责人: LINDA CHANG
• 金额: $ 55.8万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-15 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9493185
• 关键词: AIDS Dementia Complex; AIDS prevention; Activities of Daily Living; Address; Adult; Aging; Alcohol abuse; Alcohols; Alleles; Anti-Inflammatory Agents; Anti-inflammatory; Attention; Attention deficit hyperactivity disorder; Attentional deficit; Back; Biological Markers; Brain; CCL2 gene; CXCL10 gene; Cannabis; Caring; Cerebrospinal Fluid; Chemotactic Factors; Child; Cognition; Cognitive; Cognitive deficits; Computers; Consent; Dependence; Double-Blind Method; E-learning; Effectiveness; Fractalkine; Functional Magnetic Resonance Imaging; Functional disorder; Future; Genes; Genetic study; Goals; HIV; HIV Seronegativity; HIV Seropositivity; HIV therapy; HIV-associated neurocognitive disorder; Heterozygote; High Prevalence; IL8 gene; Incidence; Individual; Infection; Institutes; Interleukin-1; Intervention; Lead; Learning; Maintenance; Marijuana; Marijuana Abuse; Memory; Memory impairment; Mind; Occupational; Patient Care; Patients; Placebos; Prevalence; Research Project Grants; Risk; SNP genotyping; Short-Term Memory; Signal Transduction; Spinal Puncture; Stroke; Substance abuse problem; System; Training; Training Programs; Variant; Verbal Learning; Visual; Visual attention; aging population; antiretroviral therapy; base; blood oxygen level dependent; cognitive function; cognitive performance; cognitive testing; cognitive training; cost; cytokine; disability; effective therapy; frontal lobe; improved; innovation; medication compliance; memory process; memory recognition; monoamine; nervous system disorder; neural correlate; neuroinflammation; normal aging; novel; placebo controlled study; psychostimulant; search engine; stimulant abuse; transcription factor; treatment planning

DESCRIPTION (provided by applicant): Despite the wide availability of potent antiretroviral therapy, up to 50% of HIV-infected individuals continue to demonstrate milder forms of HIV-associated neurocognitive disorders (HAND). With the increasing aging population of HIV-infected patients who are at greater risk for developing HAND, the cost of care may nearly double in the next two decades. Co-morbid issues such as alcohol, marijuana or psychostimulant abuse, which occur at much higher prevalence amongst HIV patients, can further exacerbate their cognitive deficits. Since effective treatment and preventions for HAND are still lacking, developing effective treatments or adjunctive therapy for these patients are critical. Working memory (WM) and attention deficits are common and may underlie cognitive deficits that lead to HAND. Therefore, we propose to evaluate the efficacy of an adaptive WM computer based training program called Cogmed. Effectiveness of adaptive WM training was shown in children with attention deficit and hyperactivity disorder (ADHD), and in adults with other neurological disorders, but has not been evaluated in HIV-positive subjects. WM deficits also may be related to neuroinflammation, frontal lobe dysfunction or decreased dopaminergic function. Therefore, the aims of this proposal are: 1) To perform a double blind placebo-controlled study using Cogmed™ to determine whether the intensive adaptive WM training will lead to greater improvement (gain) on WM and other cognitive functions (transfer of gain) in HIV-infected individuals and in HIV-seronegative (SN) controls than fixed low level (placebo) training, at one-month and at six months after training (maintenance of gain). 2) To assess the neural correlates of WM training: Whether brain activation will improve, at 1-month and 6-months after the training, on BOLD-fMRI during WM and attention. 3) Since individuals with the AA genotype for the SNP (rs4657412) for LMX1A showed greater magnitudes of training-related gains in verbal WM in a prior study, we will assess our subjects for this allelic variation on thei training effects (gain and maintenance). Lastly, we will assess changes in neuroinflammatory markers and monoamine metabolites in the CSF of those who consent to lumbar punctures before and 6 months after training, and evaluate the relationships between these CSF makers, cognitive performance and training effects, as well as brain activation fMRI. Although Cogmed™ is not a "cure" for HAND, this research project may identify a new and effective adjunctive therapy to improve cognitive function and hence these patients' activities of daily living and functioning. Our genetic study may identify individuals who might benefit the most from the WM training, and therefore help to guide future treatment plans for HIV-infected individuals. Finally, we will also learn how brain activation, neuroinflammation and CSF monoamine levels might relate to WM function before and after the training.

描述（由适用提供）：尽管潜在的抗逆转录病毒疗法有广泛可用性，但多达50％的HIV感染者继续证明米勒形式的HIV相关神经认知疾病（HAND）。随着艾滋病毒感染患者的老龄化人群的增加，他们有更大的发展风险，在接下来的二十年中，护理费用可能几乎翻了一番。在艾滋病毒患者中发生的饮酒，大麻或精神刺激滥用等合并症，例如艾滋病毒患者的患病率要高得多，可能会进一步加剧其认知缺陷。由于仍然缺乏有效的治疗和手动预防，因此为这些患者开发有效的治疗或辅助治疗至关重要。工作记忆（WM）和注意力缺陷很常见，可能是导致手的认知缺陷的基础。因此，我们建议评估称为CogMed的自适应WM计算机培训计划的有效性。自适应WM训练的有效性显示在患有注意力缺乏和多动症（ADHD）的儿童以及其他神经系统疾病的成年人中，但尚未在HIV阳性受试者中进行评估。 WM定义也可能与神经炎症，前叶功能障碍或改善的多巴胺能功能有关。因此，该提案的目的是：1）使用COGMED™进行一项双重盲安慰剂对照研究，以确定强化适应性的WM培训是否会在HIV感染的个体和HIV（SN）对照（SN）对照（固定型）训练（在固定的训练中），在六个月的培训中，在六个月的培训中，在一项训练中，在一项训练中，在一项训练中，对HIV感染的个体和六个月的培训（在一项训练中），在一项训练中，在一项训练中，在一项训练中，是否会在WM和其他认知功能（收益转移）上进行更大的改善（增益），并在一项训练中进行培训。 2）评估WM训练的神经相关性：在训练后的1个月和6个月内，大脑激活在WM和注意力期间是否会在1个月和6个月后改善。 3）由于LMX1A的SNP具有AA基因型的个体（RS4657412）在先前的研究中显示出与训练相关的培训相关收益的幅度更大，因此我们将评估我们对训练效应（增益和维持）的等位基因变异的对象。最后，我们将评估CSF中神经炎症标志物和单胺代谢产物的变化，这些人同意在训练之前和6个月后同意腰椎穿刺，并评估这些CSF制造商，认知性能和训练效果之间的关系，以及大脑激活。尽管COGMED™不是手的“治疗方法”，但该研究项目可能会确定一种新的有效的辅助疗法，以改善认知功能，从而确定这些患者的日常生活和功能。我们的遗传研究可能会确定可能从WM培训中受益最大的人，因此有助于指导感染HIV的人的未来治疗计划。最后， 我们还将学习脑部激活，神经炎症和CSF单胺水平如何与训练之前和之后的WM功能有关。