PDF(Pubmed)
Abstract：
The growing prevalence of dementia makes it important for us to better understand its pathophysiology and treatment modalities, to improve the quality of life of patients and caregivers. Alzheimer\'s disease (AD), a neurodegenerative disease, is the most common form of amnestic dementia in the geriatric population. Pathophysiology of AD is widely attributed to aggregation of amyloid-beta (Aβ) plaques and hyperphosphorylation of tau proteins. Initial treatment modalities aimed to increase brain perfusion in a non-specific manner. Subsequent therapy focused on rectifying neurotransmitter imbalance in the brain. Newer drugs modify the progression of the disease by acting against aggregated Aβ plaques. However, not all drugs used in therapy of AD have been granted approval by the United States Food and Drug Administration (FDA). This review categorizes and summarizes the FDA-approved drugs in the treatment of AD in a manner that would make it a convenient reference for researchers and practicing physicians alike. Drugs that mitigate symptoms of dementia may be categorized into mitigators of Behavioral and Psychological Symptoms of Dementia (BPSD), and mitigators of cognitive decline. BPSD mitigators include brexpiprazole, an atypical antipsychotic with a once-daily dosage suited to treat agitation in dementia patients, and suvorexant, an orexin receptor antagonist used to treat sleep disturbances. Cognitive decline mitigators include cholinesterase inhibitors such as donepezil, rivastigmine, and galantamine and glutamate inhibitors such as memantine. Donepezil is the most commonly prescribed drug. It is cheap, well-tolerated, and may be prescribed orally once daily, or as a transdermal patch once weekly. It increases ACh levels, enhances oligodendrocyte differentiation and also protects against Aβ toxicity. However, regular cardiac monitoring is required due to reports of cardiac conduction side effects. Rivastigmine requires a twice-daily oral dosage or once-daily replacement of transdermal patch. It has fewer cardiac side effects than donepezil, but local application-site reactions have been noted. Galantamine, in addition to improving cognitive symptoms in a short span of time, also delays the development of BPSDs and has minimal drug-drug interactions by virtue of having multiple metabolic pathways. However, cardiac conduction disturbances must be closely monitored for. Memantine, a glutamate regulator, acts as an anti-Parkinsonian agent and an antidepressant, in addition to improving cognition and neuroprotection, and requires a once-daily dosage in the form of immediate-release or sustained-release oral tablets. Disease-modifying drugs such as aducanumab and lecanemab reduce the Aβ burden. Both act by binding with fibrillary conformations of Aβ plaques in the brain. These drugs have a risk of causing amyloid-related imaging abnormalities, especially in persons with ApoE4 gene. Aducanumab is administered once every 4 weeks and lecanemab once every 2 weeks. The decision on the choice of the drug must be made after considering the availability of drug, compliance of patient (once-daily vs. multiple doses daily), cost, specific comorbidities, and the risk-benefit ratio for the particular patient. Other non-pharmacological treatment modalities must also be adopted to have a holistic approach toward the treatment of AD.
摘要：
痴呆症的患病率越来越高，因此我们必须更好地了解其病理生理学和治疗方式，改善患者和护理人员的生活质量。阿尔茨海默病（AD），一种神经退行性疾病,是老年人群中最常见的遗忘型痴呆。AD的病理生理学广泛归因于淀粉样β(Aβ)斑块的聚集和tau蛋白的过度磷酸化。初始治疗模式旨在以非特异性方式增加脑灌注。随后的治疗重点是纠正大脑中的神经递质失衡。较新的药物通过对抗聚集的Aβ斑块来改变疾病的进展。然而,并非所有用于治疗AD的药物都获得了美国食品和药物管理局(FDA)的批准.这篇综述对FDA批准的治疗AD的药物进行了分类和总结，使其成为研究人员和执业医师的方便参考。缓解痴呆症症状的药物可以分为痴呆症行为和心理症状缓解剂（BPSD），和认知衰退的缓解剂。BPSD缓解剂包括布立哌唑，一种非典型抗精神病药物，每日一次的剂量适合治疗痴呆患者的躁动，还有Suvorexant,一种用于治疗睡眠障碍的食欲素受体拮抗剂。认知衰退缓解剂包括胆碱酯酶抑制剂，如多奈哌齐，利伐斯的明,加兰他敏和谷氨酸抑制剂如美金刚。多奈哌齐是最常用的处方药。它很便宜，耐受性良好,并且可以每天口服一次，或作为透皮贴剂每周一次。它增加了ACh水平，增强少突胶质细胞分化并防止Aβ毒性。然而,由于心脏传导副作用的报告，需要定期心脏监测。卡巴拉汀需要每日两次口服剂量或每日一次替换透皮贴剂。它的心脏副作用比多奈哌齐少，但已注意到局部应用现场反应。加兰他敏,除了在短时间内改善认知症状，还延迟了BPSD的发展，并且由于具有多个代谢途径而具有最小的药物-药物相互作用。然而,心脏传导紊乱必须密切监测。美金刚,谷氨酸调节剂,作为抗帕金森病药物和抗抑郁药，除了改善认知和神经保护，并且需要以立即释放或持续释放口服片剂形式的每日一次剂量。诸如aducanumab和lecanemab之类的疾病改善药物可降低Aβ负担。两者都通过与大脑中Aβ斑块的原纤维构象结合而起作用。这些药物有引起淀粉样蛋白相关成像异常的风险,尤其是有ApoE4基因的人.Aducanumab每4周施用一次，lecanemab每2周施用一次。药物的选择必须在考虑药物的可用性后做出决定，患者的依从性(每天一次vs.每日多剂量)，成本,特定的合并症，以及特定患者的风险收益比。还必须采用其他非药物治疗方式以具有治疗AD的整体方法。
