Tomaszewski S, Gauthier S, Wimo A, Rosa-Neto P
Serge Gauthier, McGill Center for Studies in Aging, Douglas Mental Health University Institute, Douglas Hospital, Verdun, QC, Canada. Phone: +1 514-766-2010; Fax: +1 514-888-4050. Email:
J Prev Alzheimers Dis. 2016;3(3):164-172. doi: 10.14283/jpad.2015.85.
Current drugs for treatment of mild to severe dementia of the Alzheimer's type include cholinesterase inhibitors and the NMDA non-competitive receptor antagonist memantine. There is controversy as to the additive benefit of these symptomatic drugs, and their effects are clinically modest. Patients with Alzheimer's disease (AD) are known to have characteristic pathology, including senile plaques with amyloid beta-protein aggregates and neurofibrillary tangles with assembled tau proteins, which start in the hippocampus and spread to neighboring areas. Amyloid and tau modifying drugs are under clinical testing. Based on this pathophysiology, it is crucial to investigate whether anti-amyloid and anti-tau combined therapy would show efficacy in early stage of AD, beyond what could be achieved with anti-amyloid or anti-tau monotherapy. It is equally important to consider the socio-economic implications of such a combination therapy, if effective. We hypothesize that the high costs of combination therapy for early-stage AD patients will require societal and public health initiatives to ensure universal access to AD treatment. In order to better predict these socio-economic implications, we summarize the management of other combination therapies used for tuberculosis, HIV/AIDS, and breast cancer, based on a database search of PubMed and other relevant sources. We put forward a framework for testing a potential anti-amyloid and anti-tau disease modifying combination therapy for early-stage AD patients and present an analysis of the socio-economic implications of such a combination therapy.
目前用于治疗轻至重度阿尔茨海默病型痴呆的药物包括胆碱酯酶抑制剂和N-甲基-D-天冬氨酸（NMDA）非竞争性受体拮抗剂美金刚。关于这些对症药物的附加益处存在争议，而且它们的临床效果有限。已知阿尔茨海默病（AD）患者具有特征性病理改变，包括含有β-淀粉样蛋白聚集体的老年斑和含有组装tau蛋白的神经原纤维缠结，这些病变始于海马体并扩散至邻近区域。淀粉样蛋白和tau蛋白修饰药物正在进行临床试验。基于这种病理生理学，研究抗淀粉样蛋白和抗tau蛋白联合治疗在AD早期是否比抗淀粉样蛋白或抗tau蛋白单一疗法更有效至关重要。同样重要的是，如果联合治疗有效，要考虑其社会经济影响。我们假设，早期AD患者联合治疗的高昂成本将需要社会和公共卫生举措来确保普遍获得AD治疗。为了更好地预测这些社会经济影响，我们基于对PubMed和其他相关来源的数据库搜索，总结了用于治疗结核病、艾滋病毒/艾滋病和乳腺癌的其他联合治疗的管理情况。我们提出了一个框架，用于测试针对早期AD患者的潜在抗淀粉样蛋白和抗tau蛋白疾病修饰联合治疗，并对这种联合治疗的社会经济影响进行分析。
