Mechanisms of chemotherapy-induced cognitive disorders: neuropsychological, pathophysiological, and neuroimaging perspectives.
Mechanisms of chemotherapy-induced cognitive disorders: neuropsychological, pathophysiological, and neuroimaging perspectives.
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发表时间：
2003-10
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通讯作者：
A. Saykin;T. Ahles;B. McDonald
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作者：
A. Saykin;T. Ahles;B. McDonald
最近的研究表明，癌症化疗后经常出现神经心理缺陷和认知功能障碍。大多数早期报告是回顾性的，但前瞻性纵向研究正在进行中。虽然现有的证据表明，一个相当分散的变化模式，记忆和执行功能可能会优先受到影响。初步数据还表明，有些人可能比其他人更容易受到伤害，从而导致对遗传和其他风险因素的调查。我们对化疗相关认知变化的认识中最大的差距是缺乏对导致观察到的变化的机制的理解。几种病理生理学候选物包括导致脑灰质（GM）萎缩和/或白色物质（WM）纤维脱髓鞘的直接神经毒性作用、引起炎症反应的继发性免疫反应和微血管损伤。神经递质水平和代谢物的改变可能构成与神经毒性作用有关的另一种机制。先进的脑成像技术可以直接或间接地评估许多这些机制，但迄今为止，这些工具的应用非常有限。形态测量磁共振成像（MRI），功能性MRI（fMRI），扩散张量成像（DTI）和磁共振波谱（MRS）是非侵入性技术，可以产生重要的补充数据的性质化疗后的神经变化。电生理学研究和正电子发射断层扫描（PET）靶向分子成像也可以提供独特的信息。我们回顾了目前可用的最小成像数据，并注意到其他脑部疾病或治疗效果的研究，这些研究可能作为成像化疗引起的变化的模型。需要大规模的前瞻性研究来帮助分离与化疗相关的认知缺陷的病理生理机制。
Recent studies have indicated the frequent occurrence of neuropsychologic deficits and cognitive complaints after systemic cancer chemotherapy. Most early reports were retrospective, but prospective longitudinal studies are underway. Although the available evidence suggests a fairly diffuse pattern of changes, memory and executive functions could be preferentially affected. Preliminary data also suggest that some individuals might be more vulnerable than others, leading to investigation of genetic and other risk factors. The greatest gap in our knowledge regarding chemotherapy-related cognitive changes is a lack of understanding of the mechanism or mechanisms that account for the observed changes. Several pathophysiological candidates include direct neurotoxic effects leading to atrophy of cerebral gray matter (GM) and/or demyelination of white matter (WM) fibers, secondary immunologic responses causing inflammatory reactions, and microvascular injury. Altered neurotransmitter levels and metabolites could constitute an additional mechanism related to neurotoxic effects. Advanced brain imaging techniques can directly or indirectly assess many of these mechanisms, but to date there has been very limited application of these tools. Morphometric magnetic resonance imaging (MRI), functional MRI (fMRI), diffusion tensor imaging (DTI), and MR spectroscopy (MRS) are noninvasive techniques that could yield important complementary data regarding the nature of neural changes after chemotherapy. Electrophysiological studies and targeted molecular imaging with positron emission tomography (PET) could also provide unique information. We review the minimal imaging data available at present and also note studies of other brain disorders or treatment effects that might serve as a model for imaging chemotherapy-induced changes. Large-scale prospective studies are needed to help isolate the pathophysiological mechanisms underlying the cognitive deficits associated with chemotherapy.