Yiannopoulou Konstantina G, Papageorgiou Sokratis G
Memory Center, Neurological Department, Henry Dunant Hospital Center, Athens, Greece.
Cognitive Disorders/Dementia Unit, 2nd Neurological Department, National and Kapodistrian University of Athens, Attikon General University Hospital, Athens, Greece.
J Cent Nerv Syst Dis. 2020 Feb 29;12:1179573520907397. doi: 10.1177/1179573520907397. eCollection 2020.
Disease-modifying treatment strategies for Alzheimer disease (AD) are still under extensive research. Nowadays, only symptomatic treatments exist for this disease, all trying to counterbalance the neurotransmitter disturbance: 3 cholinesterase inhibitors and memantine. To block the progression of the disease, therapeutic agents are supposed to interfere with the pathogenic steps responsible for the clinical symptoms, classically including the deposition of extracellular amyloid β plaques and intracellular neurofibrillary tangle formation. Other underlying mechanisms are targeted by neuroprotective, anti-inflammatory, growth factor promotive, metabolic efficacious agents and stem cell therapies. Recent therapies have integrated multiple new features such as novel biomarkers, new neuropsychological outcomes, enrollment of earlier populations in the course of the disease, and innovative trial designs. In the near future different specific agents for every patient might be used in a "precision medicine" context, where aberrant biomarkers accompanied with a particular pattern of neuropsychological and neuroimaging findings could determine a specific treatment regimen within a customized therapeutic framework. In this review, we discuss potential disease-modifying therapies that are currently being studied and potential individualized therapeutic frameworks that can be proved beneficial for patients with AD.
阿尔茨海默病(AD)的疾病修饰治疗策略仍在广泛研究中。目前,针对这种疾病只有对症治疗方法,所有这些方法都试图平衡神经递质紊乱:3种胆碱酯酶抑制剂和美金刚。为了阻止疾病进展,治疗药物应该干扰导致临床症状的致病步骤,传统上包括细胞外淀粉样β斑块的沉积和细胞内神经原纤维缠结的形成。其他潜在机制则通过神经保护、抗炎、生长因子促进、代谢有效药物和干细胞疗法来靶向。最近的治疗方法整合了多个新特点,如新型生物标志物、新的神经心理学结果、在疾病过程中纳入更早阶段的人群以及创新的试验设计。在不久的将来,可能会在“精准医学”背景下为每个患者使用不同的特定药物,其中异常的生物标志物伴随着特定模式的神经心理学和神经影像学发现,可以在定制的治疗框架内确定特定的治疗方案。在这篇综述中,我们讨论了目前正在研究的潜在疾病修饰疗法以及可能被证明对AD患者有益的潜在个体化治疗框架。