Decreased brain dopamine transporters are related to cognitive deficits in HIV patients with or without cocaine abuse
Decreased brain dopamine transporters are related to cognitive deficits in HIV patients with or without cocaine abuse
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DOI：
10.1016/j.neuroimage.2008.05.011
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发表时间：
2008-08-15
期刊：
影响因子：
5.7
通讯作者：
Fowler, Joanna S.
中科院分区：
文献类型：
--
作者：
Chang, Linda;Wang, Gene-Jack;Fowler, Joanna S.
目的：人类免疫缺陷病毒（HIV）相关性痴呆患者基底神经节多巴胺转运蛋白（DAT）减少。因此，我们评估了纹状体DAT和多巴胺D2受体（D2 R）可用性与认知能力之间的关系，以及可卡因滥用（HIV患者中常见的共病状态）是否与DAT和D2受体的进一步降低相关。方法：35名HIV阳性受试者[24名无（HIV）和11名有可卡因依赖史（HIV+Coc）]和14名血清阴性对照（SN）接受PET评估，以使用[C-使用[C-11]雷氯必利的可卡因和D2 R结果：与SN对照组相比，两组HIV受试者在壳核中的DAT较低，（HIV+Coc：-16.7%，p = 0.003; HIV：-12.2%，p = 0.02），仅HIV+Coc在尾状核中显示较低的DAT（-12.2%，p = 0.04）。两个HIV组的两个区域中较低的D2 R是由更多的尼古丁使用引起的。较低的DAT，但不是D2 R，在壳核和尾状核与较差的性能油多项神经心理学测试，校正年龄的影响。教育、智力、情绪和尼古丁使用。此外，结构方程模型（SEM）表明，较低的平均多巴胺功能（DAT和D2 R）与神经心理学测试中较差的总体功能有关（p = 0.05）。解释：多巴胺能功能下降可能导致HIV患者的认知功能障碍，无论是否额外滥用可卡因。这些发现表明，这些HIV患者可能受益于增强多巴胺功能的治疗，即保护多巴胺细胞免受损伤。(C)2008年爱思唯尔公司All rights reserved.
Objective: Decreased dopamine transporters (DAT) in the basal ganglia were shown in patients with human immunodeficiency virus (HIV) associated dementia. Therefore, we assessed the relationship between striatal DAT and dopamine D2 receptors (D2R) availability and cognitive performance, and whether cocaine abuse, a common co-morbid condition in HIV patients, would be associated with further decreases in DAT and D2 receptors.Methods: 35 HIV-positive subjects [24 without (HIV) and 11 with a history of cocaine-dependence (HIV+Coc)] and 14 seronegative controls (SN) were evaluated with PET to measure DAT using [C-11]cocaine and D2R using [C-11]raclopride (availability of DAT or D2R estimated with Bmax/Kd), and a battery of neuropsychological tests.Results: Compared to SN controls, both HIV subject groups had lower DAT in putamen (HIV+Coc: - 16.7%, p = 0.003; HIV: - 12.2%, p = 0.02) and only HIV+Coc showed lower DAT in caudate (- 12.2%, p = 0.04). Lower D2R in both regions of both HIV groups were accounted by the greater nicotine use. Lower DAT, but not D2R, in putamen and caudate were associated with poorer performance oil Multiple neuropsychological tests, corrected for the effects of age. education, intelligence, mood, and nicotine use. Furthermore, a structural equation model (SEM) indicated that lower average dopamine function (both DAT and D2R) were related to poorer overall function oil neuropsychological tests (p = 0.05).Interpretation: Reduced dopaminergic function may contribute to cognitive dysfunction in HIV patients with or without additional cocaine abuse. These findings suggest that these HIV patients may benefit from treatments that enhance dopamine function OF protection from dopamine cell injury. (C) 2008 Elsevier Inc. All rights reserved.