SuperAging in HIV-infected Adults: Biopsychosocial Predictors of Neurocognitive Aging Trajectories

项目摘要/摘要 接受抗逆转录病毒疗法(ART)的艾滋病毒携带者(PLWH)的预期寿命稳步上升 增加，在美国估计有50%的PLWH年龄在50岁及以上。尽管美国人的寿命延长了 在ART时代，老年PLWH过早和加速发展为老年性心脏病的风险增加 症状，包括神经认知障碍(NCI)、虚弱和日常功能依赖。神经性艾滋病毒 研究优先研究艾滋病毒的复合神经生物学负担引起的不良后果 和老龄化；然而，三分之一到三分之二的老年PLWH不符合NCI的标准。尽管神经认知 神经认知未受损的老年PLWH之间的异质性，神经认知的个体差异 人们对衰老的轨迹知之甚少。我们最近描述了一组较老的PLWH的特征 年轻的神经认知能力类似于健康的25岁，在这个年龄，大多数神经认知能力 匹克。这些被称为超级老年人(SA)的神经认知精英显示出类似的艾滋病毒特征 疾病严重程度与认知正常、非超级和认知受损的同龄人相比，尚未 有更好的日常功能，与心理和身体健康相关的生活质量，更少的合并症，更高 病前智商。这些发现与认知和生理储备的模型一致，表明健壮的 认知和生理资源的维护使SA能够有效地对抗神经和生理 艾滋病毒感染导致衰老的压力源。然而，这些横截面数据并没有说明SA是否保持 随着时间的推移，最大的神经认知能力，以及这种神经认知弹性是否与整体一致 生物、心理和社会储备指标。评估SA作为反映抵抗能力的结构的有效性 神经认知功能减退对确定易感人群中的神经保护因素至关重要 较老的PLWH。因此，拟议的F31项目旨在1)表征神经认知老化轨迹 2)确定神经认知的生物-心理-社会预测因子 轨迹；以及3)检查人口统计学、神经精神病学、物质使用和日常生活的潜在影响 神经认知轨迹的功能因素。拟议的研究将采用潜在增长混合物。 利用中枢神经系统HIV抗逆转录病毒治疗效果中老年PLWH的纵向档案数据进行建模 研究计划。通过F31机制提供的机会将有助于申请者 向独立的学术神经心理学家的职业发展 促进老年PLWH的神经认知弹性。

PROJECT SUMMARY/ABSTRACT The life expectancy of people living with HIV (PLWH) receiving antiretroviral therapy (ART) has steadily increased, with an estimated 50% of PLWH in the U.S. aged 50 years and older. Despite increased longevity in the ART-era, older PLWH are at enhanced risk for premature and accelerated development of geriatric syndromes, including neurocognitive impairment (NCI), frailty, and daily functioning dependence. NeuroHIV research preferentially studies adverse outcomes stemming from the combined neurobiological burdens of HIV and aging; however, one to two-thirds of older PLWH do not meet criteria for NCI. Despite the neurocognitive heterogeneity among neurocognitively `unimpaired' older PLWH, inter-individual differences in neurocognitive aging trajectories are poorly understood. We have recently characterized a subgroup of older PLWH with youthful neurocognition akin to that of a healthy 25 year-old, an age at which most neurocognitive capacities peak. These neurocognitively elite individuals, termed SuperAgers (SA), display comparable profiles of HIV disease severity as compared to their cognitively normal non-super and cognitively impaired counterparts, yet have better daily functioning, mental and physical health-related quality of life, fewer comorbidities, and higher premorbid IQ. These findings align with a model of cognitive and physiological reserve, suggesting that robust maintenance of cognitive and physiological resources enables SA to effectively combat the neural and physical stressors of aging with HIV. Nevertheless, these cross-sectional data do not address whether SA maintain maximal neurocognition over time, and whether such neurocognitive resilience converges with holistic indicators of biopsychosocial reserve. Assessing the validity of SA as a construct reflecting resilience against neurocognitive decline is critical toward identifying neuroprotective factors among the vulnerable population of older PLWH. Accordingly, the proposed F31 project aims to 1) characterize neurocognitive aging trajectories and determine their relation to SA in older PLWH; 2) determine biopsychosocial predictors of neurocognitive trajectories; and 3) examine potential effects of demographic, neuropsychiatric, substance use, and daily functioning factors on neurocognitive trajectories. The proposed research will employ latent growth mixture modeling using longitudinal, archival data of older PLWH from the CNS HIV Antiretroviral Therapy Effects Research program. The opportunities afforded via this F31 mechanism will facilitate the applicant's professional development toward becoming an independent academic neuropsychologist dedicated to promoting neurocognitive resilience among older PLWH.