Forlenza Orestes V, Aprahamian Ivan, de Paula Vanessa J, Hajek Tomas
Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo. Rua Dr. Ovídio Pires de Campos 785, 05403-010 - São Paulo, SP, Brazil..
Curr Alzheimer Res. 2016;13(8):879-86. doi: 10.2174/1567205013666160219112854.
Preclinical studies have shown that lithium modifies pathological cascades implicated in certain neurodegenerative disorders, such as Alzheimer's disease (AD), Huntigton`s disease (HD), multiple system atrophy (MSA) and amyotrophic lateral sclerosis (ALS). A critical question is whether these pharmacodynamic properties of lithium translate into neurodegenerative diseases modifying effects in human subjects.
We reviewed all English controlled clinical trials published in PubMed, PsycINFO, Embase, SCOPUS, ISI-Web with the use of lithium for the treatment of neurodegenerative disorders between July 2004 and July 2014.
Lithium showed evidence for positive effects on cognitive functions and biomarkers in amnestic mild cognitive impairment (aMCI, 1 study) and AD (2 studies), even with doses lower than those used for mood stabilisation. Studies of Li in HD, MSA and CSI did not show benefits of lithium. However, due to methodological limitations and small sample size, these studies may be inconclusive. Studies in ALS showed consistently negative results and presented evidence against the use of lithium for the treatment of this disease.
In absence of disease modifying treatments for any neurodegenerative disorders, the fact that at least 3 studies supported the effect of lithium in aMCI/AD is noteworthy. Future studies should focus on defining the dose range necessary for neuroprotective effects to occur.
临床前研究表明，锂可改变某些神经退行性疾病（如阿尔茨海默病（AD）、亨廷顿舞蹈病（HD）、多系统萎缩（MSA）和肌萎缩侧索硬化症（ALS））中涉及的病理级联反应。一个关键问题是锂的这些药效学特性是否能转化为对人类受试者神经退行性疾病的改善作用。
我们检索了2004年7月至2014年7月期间发表在PubMed、PsycINFO、Embase、SCOPUS、ISI-Web上所有使用锂治疗神经退行性疾病的英文对照临床试验。
锂对遗忘型轻度认知障碍（aMCI，1项研究）和AD（2项研究）的认知功能和生物标志物显示出积极作用，即使使用的剂量低于用于稳定情绪的剂量。锂在HD、MSA和CSI方面的研究未显示出益处。然而，由于方法学上的局限性和样本量小，这些研究可能尚无定论。ALS方面的研究结果始终为阴性，并提供了反对使用锂治疗该疾病的证据。
在没有针对任何神经退行性疾病的疾病改善治疗方法的情况下，至少有3项研究支持锂对aMCI/AD的作用这一事实值得注意。未来的研究应集中于确定产生神经保护作用所需的剂量范围。
