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（由申请人提供）：尽管有效的抗逆转录病毒疗法已被广泛使用，但随着艾滋病毒感染者人口老龄化的增加，高达 50% 的艾滋病毒感染者仍然表现出较轻微的艾滋病毒相关神经认知障碍 (HAND)。对于那些患 HAND 的风险更大的人来说，未来二十年的护理费用可能会增加近一倍。 酒精、大麻或精神兴奋剂滥用等共病问题在这些人群中的发生率要高得多。 HIV 患者的认知缺陷可能会进一步恶化，因为仍然缺乏针对 HAND 的有效治疗和预防措施，因此为这些患者开发有效的治疗或辅助疗法至关重要，工作记忆 (WM) 和注意力缺陷很常见，并且可能是导致认知缺陷的原因。因此，我们建议评估基于计算机的适应性 WM 训练计划（称为 Cogmed）的有效性。适应性 WM 训练的有效性已在患有注意力缺陷多动障碍 (ADHD) 的儿童以及患有其他神经系统疾病的成人中得到证实。还没有已在 HIV 阳性受试者中进行了评估。WM 缺陷也可能与神经炎症、额叶功能障碍或多巴胺能功能下降有关。因此，本提案的目的是：1) 使用 Cogmed™ 进行双盲安慰剂对照研究。确定强化适应性 WM 训练是否会导致 HIV 感染者和 HIV 血清阴性 (SN) 对照的 WM 和其他认知功能（增益转移）比固定低水平有更大的改善（增益） （安慰剂）训练，训练后 1 个月和 6 个月（维持增益） 2) 评估 WM 训练的神经相关性：训练后 1 个月和 6 个月时大脑激活是否会改善， 3) 由于 LMX1A 的 SNP (rs4657412) AA 基因型的个体在先前的研究中在言语 WM 方面表现出更大程度的与训练相关的增益，我们将评估受试者的等位基因变异对训练效果（增益和维持）的影响。最后，我们将评估那些同意在训练前和训练后 6 个月进行腰椎穿刺的受试者脑脊液中神经炎症标志物和单胺代谢物的变化。这些 CSF 制造者、认知表现和训练效果以及大脑激活功能磁共振成像 (fMRI) 之间的关系 虽然 Cogmed™ 不是 HAND 的“治愈方法”，但该研究项目可能会找到一种新的有效辅助疗法来改善。认知功能以及这些患者的日常生活和功能活动可以确定哪些人可能从 WM 培训中受益最多，从而有助于指导 HIV 感染者的未来治疗计划。 我们还将了解训练前后大脑激活、神经炎症和脑脊液单胺水平如何与 WM 功能相关。