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管理的疾病。许多出生时感染艾滋病毒的儿童，以前寿命很短，现在都能活到成年。这就需要更充分地了解这些青年在成为独立、有生产力的成年人时遇到的障碍。在成人中，HIV通常与记忆和执行功能（如抑制、认知灵活性和解决问题）的损伤有关，这增加了日常功能问题的风险，包括药物不依从性。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非常有限，而且没有一个包括前瞻性记忆（即执行未来意图的能力）的测量，这是一个特别可靠的预测成人艾滋病毒感染者日常功能的指标。此外，我们目前对HIV对大脑发育的功能影响的理解是有限的。本研究将首次在重要功能结果的背景下评估发育和HIV感染对记忆和执行功能的复杂相互作用，以努力推进儿科神经艾滋病的临床科学。该研究将验证以下假设：1)围产期获得的艾滋病毒与记忆和执行功能缺陷有关；2)艾滋病毒的严重程度和病史，包括疾病最严重时的年龄，将与记忆和执行功能的损害程度有关；3)随着时间的推移，发育变化和艾滋病毒严重程度的变化将相互作用，影响这些功能；4)记忆和执行功能的损伤会导致日常功能的问题（包括药物依从性、学习成绩和适应性行为）。使用纵向设计来检查和控制青春期这些功能的发展变化，我们将在两个时间点（间隔两年）对200名艾滋病毒感染者和75名未感染的9-18岁青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的测量。数据将在8个地点收集，这些地点参与了一项大型的全国性围产期HIV感染结果纵向研究，即儿童HIV/艾滋病队列研究青少年总方案，从而使我们能够在围产期HIV感染的人口统计学、健康相关、认知和行为方面的更大背景下，以有效和具有成本效益的方式检查记忆和执行功能。这是一个重要的研究领域，因为艾滋病毒青年的记忆和执行功能缺陷可能对他们在成年后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的影响。我们预计这项研究不仅将阐明围产期获得性艾滋病毒的发育神经认知方面，而且还将为围产期感染艾滋病毒的青少年提供重要的信息和额外的工具，以针对有不良功能结局风险的围产期艾滋病毒感染的目标领域进行干预。