Neuropsychological Benefits of Cognitive Training in Ugandan HIV Children

描述(由申请者提供)：研究主题：超过11万名乌干达儿童因中枢神经系统艾滋病毒感染的进行性脑病而面临神经认知障碍的风险。即使临床情况稳定，这些儿童也可能有运动、注意力、记忆、视觉空间处理和其他执行功能障碍。乌干达卡云加区的150名感染艾滋病毒的学龄儿童将成为我们的参与者。这些儿童中的50名将被随机选择接受24次计算机认知康复治疗(CCRT)项目的培训，该项目名为船长日志，主要针对有注意力或学习问题的美国儿童。不以循序渐进的方式指导孩子进行训练的锁定版本的船长日志将被管理给第二个“主动控制”组；而第三组将是不接受任何计算机训练干预的被动控制组。研究目的1：在8周和3个月的随访期内，比较船长日志CCRT与主动对照组和被动对照组的24次训练对神经心理的影响。研究目的2：比较24次舰长日志CCRT训练课程与主动控制组和被动控制组在8周和3个月随访期内的精神益处。研究目的3：评估HIV亚型、ART治疗状态以及相应的临床稳定性如何改变儿童CCRT神经心理表现的进步和精神症状的减少。结果评估：考夫曼儿童评估组合，第二版。在为期8周的训练前后和3个月的随访中，进行KABC-2、注意变量(TOVA)视觉和听觉测试、CogState计算机化神经心理筛查测试、Bruininks-Oseretsky运动能力测试(BOT-2)和Achenbach儿童行为量表(CBCL)。我们以前对感染艾滋病毒的乌干达儿童使用了所有这些评估，以有效地评估神经心理和精神问题。船长日志有一个内部评估器功能，它将帮助我们监控儿童最好地响应的具体培训任务。根据我们之前对感染艾滋病毒的Kayunga儿童的研究，我们预计在研究登记时，我们的样本中约有40%是关于ART的，大约20%将是D亚型，60%将是A亚型。我们还观察到，携带艾滋病毒A亚型的儿童患神经认知缺陷的风险更大。分析：我们将比较三个研究组在8周训练期和3个月随访期内的神经心理学和精神病学方面的进步，预计CCRT干预组的儿童(研究目标1和2)的进步将显著更大。从长远来看，这些神经心理上的收获将与学校表现的改善相关。干预：接受抗逆转录病毒治疗的儿童将比未接受抗逆转录病毒疗法的儿童获得更大的收益，而艾滋病毒D亚型儿童的病毒载量更低，淋巴细胞激活水平更高，从而从CCRT中获得更大的收益(研究目标3)。结论：CCRT将被证明在增强ART对HIV儿童的神经认知益处方面是有效和可持续的。它将被证明对资源匮乏环境中的儿童进行评估和治疗是可行的。 公共卫生意义：除了儿科艾滋病毒感染对神经发育的直接影响之外，全球数千万艾滋病毒儿童和孤儿的艾滋病毒疾病对公共卫生造成的负担是巨大的，因为它如何进一步损害家庭环境的质量和已经贫穷的儿童的教育机会。如果计算机认知训练被证明在增强艾滋病毒儿童的神经心理功能和精神健康方面是实用和有效的，那么这将支持联合国千年发展目标的第二个目标，即确保所有儿童都有最好的机会完成小学教育。计算机化的认知培训和评估还可以在整个发展中世界资源匮乏的环境中进行成本效益高的干预，因为那里没有受过训练的专业人员的特殊教育或医疗康复护理。

DESCRIPTION (provided by applicant): Research Topic: Over 110,000 HIV Ugandan children are at risk for neurocognitive disorders due to the progressive encephalopathy of CNS HIV infection. Even if clinically stable, these children can have motor, attention, memory, visual-spatial processing, and other executive function impairment. One-hundred and fifty school-age children with HIV in Kayunga District, Uganda, will serve as our participants. Fifty of these children will be randomly selected to receive 24 training sessions of a computerized cognitive rehabilitation therapy (CCRT) program called Captain's Log, marketed mostly for American children with attention or learning problems. A locked version of Captain's Log which does not direct the child's training in a progressive manner will be administered to a second "active control" group; while a third group will be a passive control group not receiving any computer training intervention. Study Aim 1: To compare the neuropsychological benefit of 24 training sessions of Captain's Log CCRT to the active and passive control groups over a 8-week period, and at 3-month follow-up. Study Aim 2: To compare the psychiatric benefit of 24 training sessions of Captain's Log CCRT to the active and passive control groups over an 8-week period, and at 3-month follow-up. Study Aim 3: To evaluate how HIV subtype, ART treatment status, and the corresponding clinical stability of the child modifies CCRT neuropsychological performance gains and psychiatric symptom reduction. Outcome Assessments: The Kaufman Assessment Battery for Children, 2nd ed. (KABC-2), Tests of Variables of Attention (TOVA) visual and auditory tests, CogState computerized neuropsychological screening test, Bruininks-Oseretsky Test of Motor Proficiency (BOT-2), and Achenbach Child Behavior Checklist (CBCL) will be administered before and after the 8-week training period and at 3-month follow-up. We have previously used all these assessments with Ugandan children with HIV to effectively evaluate neuropsychological and psychiatric problems. Captain's Log has an internal evaluator feature which will help us monitor the specific training tasks to which the children best respond. Based on our prior research with Kayunga children with HIV, we anticipate that about 40% of our sample will be on ART at study enrollment, and about 20% will be Subtype D while 60% will be subtype A. We also observed that children with HIV Subtype A are at greater risk for neurocognitive deficits. Analyses: We will compare neuropsychological and psychiatric gains over the 8-week training period and at 3-mo follow-up for our three study groups, anticipating that they will be significantly greater for the CCRT intervention children (Study Aims 1 & 2). These neuropsychological gains will be associated with improved school performance over the long-term. Intervention children on ART will have greater gains than those not on ART, and HIV subtype D children will have lower viral loads and higher lymphocyte activation levels, resulting in greater gains from CCRT (Study Aim 3). Conclusion: CCRT will prove effective and sustainable in potentiating the neurocognitive benefit of ART in HIV children. It will prove viable for assessing and treating children in resource-poor settings. PUBLIC HEALTH RELEVANCE: Beyond the direct neurodevelopmental impact of pediatric HIV infection, the public health burden of HIV disease for tens of millions of HIV children and orphans globally is monumental when considering how it further compromises quality of home environment and educational opportunity for children already impoverished. If computerized cognitive training proves practical and effective for enhancing neuropsychological function and psychiatric well-being in HIV children, then this would support the second of the UN Millennium Development Goals, which is to ensure that all children have the best opportunity to complete primary schooling. Computerized cognitive training and assessment might also allow for cost/effective interventions in resource poor settings throughout the developing world where special education or medical rehabilitative care by trained professionals are not available.