Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD.
HIV Neurobehavioral Research Program, Department of Psychiatry, School of Medicine, University of California, San Diego, La Jolla, CA.
J Acquir Immune Defic Syndr. 2019 Sep 1;82(1):61-70. doi: 10.1097/QAI.0000000000002093.
The presentation of cognitive impairments in HIV-infected individuals has transformed since the introduction of antiretroviral therapies. Although the overall prevalence of cognitive impairments has not changed considerably, frank dementia is now infrequent, and milder forms of cognitive impairments predominate. Mechanistic insights to the underlying causes of these residual cognitive impairments have been elusive, in part due to the heterogenous etiology of cognitive dysfunction in this population. Here, we sought to categorize longitudinal change in HIV-infected patients based on the performance in specific cognitive domains.
This study consisted of 193 participants from the CHARTER cohort with detailed demographic, clinical, and neuropsychological testing data obtained from 2 study visits interspersed by ∼6 months. Cognitive testing assessed executive function, learning and delayed recall, working memory, verbal fluency, speed of information processing, and motor skills. Change scores were calculated for each domain between the 2 study visits. Dimension reduction and clustering was accomplished by principal component analysis of change scores and k-means clustering to identify cognitive domains that group together and groups of subjects with similar patterns of change.
We identified 4 distinct cognitive change phenotypes that included declines in: (1) verbal fluency, (2) executive function (3) learning and recall, and (4) motor function, with approximately equal numbers of participants in each phenotype.
Each of the 4 cognitive change phenotypes identify deficits that imply perturbations in specific neural networks. Future studies will need to validate if cognitive change phenotypes are associated with alterations in associated neural pathways.
自抗逆转录病毒疗法问世以来，HIV 感染者认知障碍的表现形式发生了变化。尽管认知障碍的总体患病率没有显著变化，但明显的痴呆症现在已经很少见，而更轻微的认知障碍则更为常见。这些残留认知障碍的潜在原因的机制研究一直难以捉摸，部分原因是该人群认知功能障碍的病因具有异质性。在这里，我们试图根据特定认知领域的表现对 HIV 感染者的纵向变化进行分类。
这项研究包括来自 CHARTER 队列的 193 名参与者，他们具有详细的人口统计学、临床和神经心理学测试数据，这些数据是从两次研究访问中获得的，两次访问之间间隔约 6 个月。认知测试评估了执行功能、学习和延迟回忆、工作记忆、语言流畅性、信息处理速度和运动技能。在两次研究访问之间，为每个领域计算了变化分数。通过对变化分数进行主成分分析和 k-均值聚类来实现维度减少和聚类，以识别出聚集在一起的认知领域和具有相似变化模式的受试者组。
我们确定了 4 种不同的认知变化表型，包括：（1）语言流畅性下降，（2）执行功能下降，（3）学习和记忆下降，以及（4）运动功能下降，每个表型的参与者数量大致相等。
这 4 种认知变化表型中的每一种都确定了缺陷，暗示特定神经网络受到干扰。未来的研究需要验证认知变化表型是否与相关神经通路的改变相关。
