Molsberry Samantha A, Lecci Fabrizio, Kingsley Lawrence, Junker Brian, Reynolds Sandra, Goodkin Karl, Levine Andrew J, Martin Eileen, Miller Eric N, Munro Cynthia A, Ragin Ann, Sacktor Ned, Becker James T
aDepartment of Psychiatry, University of Pittsburgh bDepartment of Statistics, Carnegie Mellon University, Pittsburgh cInfectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania dDepartment of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland eAIDS Healthcare Foundation, Los Angeles fDepartment of Neurology, University of California Los Angeles, California gDepartment of Psychiatry, Rush University School of Medicine, Chicago, Illinois hDepartment of Psychiatry, University of California Los Angeles, California iDepartment of Psychiatry jDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland kDepartment of Radiology Northwestern University, Evanston, Illinois lDepartment of Neurology mDepartment of Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
AIDS. 2015 Mar 27;29(6):713-21. doi: 10.1097/QAD.0000000000000561.
The longitudinal trajectories that individuals may take from a state of normal cognition to HIV-associated dementia are unknown. We applied a novel statistical methodology to identify trajectories to cognitive impairment, and factors that affected the 'closeness' of an individual to one of the canonical trajectories.
The Multicenter AIDS Cohort Study (MACS) is a four-site longitudinal study of the natural and treated history of HIV disease among gay and bisexual men.
Using data from 3892 men (both HIV-infected and HIV-uninfected) enrolled in the neuropsychology substudy of the MACS, a Mixed Membership Trajectory Model (MMTM) was applied to capture the pathways from normal cognitive function to mild impairment to severe impairment. MMTMs allow the data to identify canonical pathways and to model the effects of risk factors on an individual's 'closeness' to these trajectories.
First, we identified three distinct trajectories to cognitive impairment: 'normal aging' (low probability of mild impairment until age 60); 'premature aging' (mild impairment starting at age 45-50); and 'unhealthy' (mild impairment in 20s and 30s) profiles. Second, clinically defined AIDS, and not simply HIV disease, was associated with closeness to the premature aging trajectory, and, third, hepatitis-C infection, depression, race, recruitment cohort and confounding conditions all affected individual's closeness to these trajectories.
These results provide new insight into the natural history of cognitive dysfunction in HIV disease and provide evidence for a potential difference in the pathophysiology of the development of cognitive impairment based on trajectories to impairment.
个体从正常认知状态发展到与艾滋病相关痴呆的纵向轨迹尚不清楚。我们应用了一种新颖的统计方法来识别认知障碍的轨迹，以及影响个体与典型轨迹之一“接近程度”的因素。
多中心艾滋病队列研究（MACS）是一项针对男同性恋和双性恋男性中艾滋病自然史及治疗史的四点纵向研究。
利用参与MACS神经心理学子研究的3892名男性（包括感染HIV和未感染HIV者）的数据，应用混合成员轨迹模型（MMTM）来捕捉从正常认知功能到轻度损害再到重度损害的路径。MMTM允许数据识别典型路径，并对风险因素对个体与这些轨迹“接近程度”的影响进行建模。
首先，我们识别出三种不同的认知障碍轨迹：“正常衰老”（60岁前轻度损害可能性低）；“早衰”（45 - 50岁开始出现轻度损害）；以及“不健康”（20多岁和30多岁出现轻度损害）模式。其次，临床定义的艾滋病，而非仅仅是HIV疾病，与接近早衰轨迹相关，第三，丙型肝炎感染、抑郁、种族、招募队列和混杂状况均影响个体与这些轨迹的接近程度。
这些结果为HIV疾病认知功能障碍的自然史提供了新见解，并为基于认知障碍轨迹的认知损害发展病理生理学潜在差异提供了证据。
