Do we treat dementia of the Alzheimer type or Alzheimer's disease? Anti-dementia drugs in the era of biomarkers

Guido Dorman, Santiago O'Neill, Franco Appiani, Ignacio Flores, María Del Rosario Chiesa, Florencia Vallejos, Julian Bustin
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Abstract

Approved drug treatments for Alzheimer´s disease (AD) are symptomatic and don´t modify the disease course. These include acetylcholinesterase inhibitors (AchI) and N-methyl-D-aspartate receptor antagonist, memantine. Around 20 years ago, these drugs were approved for Alzheimer type Dementia. This wasbased on clinical trials which inclusion criteria were focused on a clinical amnestic AD presentation. At that time, subjects with an atypical AD clinical presentation or biomarkers were not included in the pharmacological trials. New biomarkers that detect amyloid and neurodegeneration have allowed us to evaluate pathological changes compatible with AD. These new advances from aclinical and biomarkers perspective allowed a diagnostic criteria update; going from an exclusively clinical criteria to one that is hybrid: clinical presentation and biomarkers based criteria.New biomarkers facilitate the early diagnosis of AD and other dementias.However, they also generate new challenges and questions regarding the adequate pharmacological treatment.There is a need for clinical trials that evaluate anti-dementia drug’s efficacy based on current diagnostic criteria (clinical profile and biomarkers) and new practice guidelines. In addition, regulatory authorities should update ACHI and memantine indications.This will help doctors to prescribe the best possible treatment for this specific population without increasing risks.

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我们治疗阿尔茨海默型痴呆或阿尔茨海默病吗?生物标志物时代的抗痴呆药物
经批准的阿尔茨海默病(AD)药物治疗是有症状的,不会改变病程。这些药物包括乙酰胆碱酯酶抑制剂(AchI)和n -甲基- d -天冬氨酸受体拮抗剂美金刚胺。大约20年前,这些药物被批准用于治疗阿尔茨海默型痴呆症。这是基于临床试验,其纳入标准集中在临床遗忘性阿尔茨海默病的表现。当时,具有非典型阿尔茨海默病临床表现或生物标志物的受试者不包括在药理学试验中。检测淀粉样蛋白和神经变性的新生物标志物使我们能够评估与AD相容的病理变化。从临床和生物标志物的角度来看,这些新进展使诊断标准得以更新;从一个完全的临床标准到一个混合的:临床表现和基于生物标志物的标准。新的生物标志物有助于阿尔茨海默病和其他痴呆症的早期诊断。然而,它们也对适当的药物治疗产生了新的挑战和问题。有必要根据现有的诊断标准(临床概况和生物标志物)和新的实践指南进行临床试验,以评估抗痴呆药物的疗效。此外,监管机构应更新ACHI和美金刚适应症。这将有助于医生在不增加风险的情况下为这一特定人群开出最佳治疗方案。
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