Memory Functioning in Children and Adolescents with Perinatal HIV Infection

围产期艾滋病毒感染儿童和青少年的记忆功能

• 批准号: 7845398
• 负责人: SHARON L NICHOLS
• 金额: $ 56.78万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-18 至 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7845398
• 关键词: AIDS neuropathy; AIDS/HIV problem; Academic achievement; Accounting; Adaptive Behaviors; Adherence; Adolescence; Adolescent; Adult; Affect; Age; Anti-Retroviral Agents; Area; Attention; Behavior; Behavioral; Birth; Brain; Caregivers; Caring; Centers for Disease Control and Prevention (U.S.); Child; Childhood; Chronic Disease; Clinical Sciences; Cognition; Cognitive; Cohort Studies; Communities; Complex; Data; Development; Diagnosis; Disease; Disease Marker; Evaluation; Failure; Future; Generations; Goals; HIV; HIV Infections; HIV-1; Health; Healthcare; Impairment; Infection; Intention; Intervention; Investigation; Knowledge; Language; Learning; Life; Literature; Longevity; Longitudinal Studies; Measures; Medical; Medication Management; Memory; Mosses; Neuraxis; Neurocognitive; Occupational; Outcome; Parents; Pattern; Performance; Perinatal; Perinatal Infection; Persons; Pharmaceutical Preparations; Pilot Projects; Population; Problem Solving; Protocols documentation; Provider; Public Health; Quality of life; Reading; Recording of previous events; Regimen; Relative (related person); Research; Research Design; Research Personnel; Resistance; Resources; Risk; Sample Size; Sampling; Self Care; Severities; Severity of illness; Short-Term Memory; Site; Speed; Staging; Task Performances; Testing; Time; Underserved Population; Verbal Learning; Viral; Virus; Visit; Youth; advanced disease; base; coping; cost; daily functioning; design; economic implication; effective intervention; executive function; falls; flexibility; functional outcomes; health economics; improved functioning; insight; longitudinal design; medication compliance; meetings; neuropathology; pediatric human immunodeficiency virus; peer; physical conditioning; prospective memory; public health relevance; skills; social; social skills; therapy development; tool; young adult

DESCRIPTION (provided by applicant): Current treatments have transformed HIV/AIDS from an inevitably fatal disease to one commonly managed as a chronic illness. Many children born with HIV infection, who previously suffered brief life spans, are now surviving into adulthood. This creates the need to understand more fully the obstacles these youth encounter in becoming independent, productive adults. In adults, HIV commonly is associated with impairments in memory and executive functions (such as inhibition, cognitive flexibility, and problem solving), which increase the risk of problems in day-to-day functioning, including medication nonadherence. Studies of memory and executive functions in children and youth with HIV infection are extremely limited, however, and none have included measures of prospective memory (that is, the ability to execute a future intention), which is a particularly robust predictor of daily functioning in adults with HIV. Furthermore, our current understanding of the functional impact of HIV on brain development is limited. The study proposed here would be the first to evaluate the complex interplay between development and HIV infection on memory and executive functions in the context of important functional outcomes in an effort to advance the clinical science of pediatric neuroAIDS. The study will test the hypotheses that: 1) perinatally acquired HIV is associated with deficits in memory and executive functioning; 2) HIV severity and history, including age at greatest disease severity, will be associated with degree of impairment in memory and executive functioning ; 3) developmental change and changes in HIV severity will interact to influence these functions over time; and 4) impairments in memory and executive function contribute to problems in daily functioning (including medication adherence, academic achievement, and adaptive behavior). Using a longitudinal design to examine and control for developmental changes in these functions during adolescence, we will administer measures of verbal and nonverbal retrospective memory, prospective memory, executive functions, and medication adherence to 200 HIV-infected and 75 uninfected youth age 9-18 at two time points, two years apart. Data will be collected at eight sites participating in a large national, longitudinal study of outcomes of perinatal HIV infection, the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol, thus allowing us to examine memory and executive functioning in an efficient and cost-effective manner in the larger context of demographic, health-related, cognitive, and behavioral aspects of perinatal HIV infection. This is an important area for investigation because deficits in memory and executive function in youth with HIV could have wide-ranging effects on their acquisition of health and medication management skills, adaptive and academic functioning, behavior, and, ultimately, social and occupational outcome in adulthood. We anticipate this study will not only elucidate developmental neurocognitive aspects of perinatally acquired HIV but will also provide important information and additional tools to target areas of intervention for perinatally HIV-infected youth at risk for poor functional outcomes. PUBLIC HEALTH RELEVANCE: This study will evaluate the effect of HIV infection acquired before or during birth on the ability of children and youth to learn and recall information, remember to perform future tasks, and manage their own attention and behavior. The data will give us valuable insight into the impact of HIV on aspects of cognitive development previously not studied. The study also will examine whether problems in memory and executive functioning affect day-to-day behavior in critical areas such as medication adherence, thus providing helpful information to design effective future interventions for youth with HIV. Strengths The study captures a well-defined population of children participating already in longitudinal observational pediatric HIV research - PHACS-AMP, thus, good data on early infection, ART regimens, CD4/VL patterns/nadir, and Stage of disease are available. The collaborative team has proposed an extremely detailed assessment of verbal/functional/memory cognition (including WRAML, verbal learning, design memory, prospective memory, memory for intentions, fluency, inhibition/interference control, problem solving, working memory, cognitive flexibility, global cognition, language, and psychomotor speed) to be conducted on 200 HIV-1 infected and 75 HIV-1 uninfected children at 2.5 and 4.5 year visits- this is a large sample size with detailed assessment. The investigators have revised the application to take into account multiple comparisons Weaknesses The study is observational and involves 2 time points - more timepoints in a subset of children for a subset of evaluations would allow assessment of consistency/stability of the assessments and whether there are specific functions or groups of children with more labile changes in function/memory. Including an intervention pilot/study to enhance memory/function while characterizing

描述（由申请人提供）：目前的治疗方法已将艾滋病毒/艾滋病从一种不可避免的致命疾病转变为一种通常作为慢性疾病进行治疗的疾病。许多出生时就感染艾滋病毒的儿童以前寿命很短，现在却能活到成年。这就需要更全面地了解这些年轻人在成为独立、富有成效的成年人时遇到的障碍。在成人中，艾滋病毒通常与记忆和执行功能（例如抑制、认知灵活性和问题解决能力）受损有关，这增加了日常功能出现问题的风险，包括不依从药物治疗。然而，对感染艾滋病毒的儿童和青少年的记忆和执行功能的研究极其有限，并且没有一项研究包括前瞻性记忆（即执行未来意图的能力）的测量，而前瞻性记忆是预测日常功能的特别有力的指标。感染艾滋病毒的成年人。此外，我们目前对艾滋病毒对大脑发育的功能影响的了解还有限。这里提出的这项研究将是第一个在重要功能结果的背景下评估发育和艾滋病毒感染之间对记忆和执行功能的复杂相互作用的研究，以努力推进儿科神经艾滋病的临床科学。该研究将检验以下假设：1）围产期感染艾滋病毒与记忆和执行功能缺陷有关； 2) HIV的严重程度和病史，包括疾病最严重的年龄，将与记忆和执行功能的损伤程度相关； 3) 随着时间的推移，发育变化和 HIV 严重程度的变化会相互作用，影响这些功能； 4) 记忆和执行功能受损会导致日常功能问题（包括药物依从性、学业成绩和适应行为）。使用纵向设计来检查和控制青春期期间这些功能的发育变化，我们将对 200 名 HIV 感染者和 75 名未感染的 9-18 岁青少年进行言语和非言语回顾性记忆、前瞻性记忆、执行功能和药物依从性测量两个时间点，相隔两年。数据将在参与围产期艾滋病毒感染结果的大型全国性纵向研究（儿科艾滋病毒/艾滋病队列研究青少年主方案）的八个地点收集，从而使我们能够以高效且具有成本效益的方式检查记忆和执行功能在围产期艾滋病毒感染的人口、健康相关、认知和行为方面的更大背景下。这是一个重要的研究领域，因为艾滋病毒青少年的记忆和执行功能缺陷可能会对他们获得健康和药物管理技能、适应和学术功能、行为以及最终的社会和职业结果产生广泛影响。成年期。我们预计这项研究不仅将阐明围产期感染艾滋病毒的发育神经认知方面的问题，还将提供重要信息和其他工具，为有功能结果不良风险的围产期艾滋病毒感染青少年提供针对性的干预领域。 公共健康相关性：本研究将评估出生前或出生期间感染艾滋病毒对儿童和青少年学习和回忆信息、记住执行未来任务以及管理自己的注意力和行为的能力的影响。这些数据将为我们提供宝贵的见解，让我们了解艾滋病毒对以前未研究过的认知发展方面的影响。该研究还将检查记忆和执行功能问题是否会影响药物依从性等关键领域的日常行为，从而为未来为感染艾滋病毒的青少年设计有效的干预措施提供有用的信息。 优势 该研究捕获了已经参与儿科 HIV 纵向观察研究 - PHACS-AMP 的明确儿童群体，因此可以获得有关早期感染、ART 方案、CD4/VL 模式/最低点和疾病阶段的良好数据。 合作团队提出了极其详细的言语/功能/记忆认知评估（包括WRAML、言语学习、设计记忆、前瞻记忆、意图记忆、流畅性、抑制/干扰控制、问题解决、工作记忆、认知灵活性、全局记忆）。认知、语言和精神运动速度）对 200 名 HIV-1 感染者和 75 名未感染 HIV-1 的儿童进行 2.5 和 4.5 年的访问——这是一个大样本量和详细的评估。 研究人员修改了应用程序以考虑多重比较 弱点 该研究是观察性的，涉及 2 个时间点 - 在儿童子集中进行更多时间点的子集评估，可以评估评估的一致性/稳定性，以及是否存在特定功能或儿童群体在功能/记忆方面存在更不稳定的变化。 包括一项干预试点/研究，以增强记忆/功能，同时表征