ImportanceSince 2018, a movement has emerged to define Alzheimer disease (AD) as a purely biological entity based on biomarker findings. The recent revision of the Alzheimer Association (AA) criteria for AD furthers this direction. However, concerns about a purely biological definition of AD being applied clinically, the understanding of AD by society at large, and the translation of blood-based biomarkers into clinical practice prompt these International Working Group (IWG) updated recommendations.ObjectiveTo consider the revised AA criteria and to offer an alternative definitional view of AD as a clinical-biological construct for clinical use. The recommendations of the 2021 IWG diagnostic criteria are updated for further elaborating at-risk and presymptomatic states.Evidence ReviewPubMed was searched for articles published between July 1, 2020, and March 1, 2024, using the terms “biomarker” OR “amyloid” OR “tau” OR “neurodegeneration” OR “preclinical” OR “CSF” OR “PET” OR “plasma” AND “Alzheimer’s disease.” The references of relevant articles were also searched.FindingsIn the new AA diagnostic criteria, AD can be defined clinically as encompassing cognitively normal people having a core 1 AD biomarker. However, recent literature shows that the majority of biomarker-positive cognitively normal individuals will not become symptomatic along a proximate timeline. In the clinical setting, disclosing a diagnosis of AD to cognitively normal people with only core 1 AD biomarkers represents the most problematic implication of a purely biological definition of the disease.Conclusions and RelevanceThe ultimate aim of the field was to foster effective AD treatments, including preventing symptoms and dementia. The approach of diagnosing AD without a clinical and biological construct would be unwarranted and potentially concerning without a clear knowledge of when or whether symptoms will ever develop. It is recommended that those who are amyloid-positive only and, more generally, most biomarker-positive cognitively normal individuals, should not be labeled as having AD. Rather, they should be considered as being at risk for AD. The expansion of presymptomatic AD is viewed as a better diagnostic construct for those with a specific pattern of biomarkers, indicating that they are proximate to the expression of symptoms in the near future.

中文翻译：

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阿尔茨海默病作为一种临床生物学结构——国际工作组建议


重要性自 2018 年以来，出现了一种运动，根据生物标志物的发现将阿尔茨海默病 （AD） 定义为纯生物实体。最近修订的阿尔茨海默病协会 （AA） AD 标准进一步推动了这一方向。然而，对临床应用 AD 的纯生物学定义的担忧、整个社会对 AD 的理解以及将基于血液的生物标志物转化为临床实践的担忧促使这些国际工作组 （IWG） 更新了这些建议。目的考虑修订后的 AA 标准，并提供 AD 作为临床使用的临床生物学结构的替代定义观点。更新了 2021 年 IWG 诊断标准的建议，以进一步详细说明风险和症状前状态。证据综述PubMed 检索了 2020 年 7 月 1 日至 2024 年 3 月 1 日期间发表的文章，使用术语“生物标志物”或“淀粉样蛋白”或“tau”或“神经退行性变”或“临床前”或“CSF”或“PET”或“血浆”和“阿尔茨海默病”。还检索了相关文章的参考文献。发现在新的 AA 诊断标准中，AD 临床上可以定义为包括具有核心 1 AD 生物标志物的认知正常人。然而，最近的文献表明，大多数生物标志物阳性的认知正常个体不会在近代内出现症状。在临床环境中，向只有核心 1 个 AD 生物标志物的认知正常人披露 AD 的诊断代表了该疾病的纯生物学定义的最有问题的含义。该领域的最终目标是促进有效的AD治疗，包括预防症状和痴呆。 在没有临床和生物学结构的情况下诊断 AD 的方法是没有根据的，并且在不清楚症状何时或是否会出现的情况下可能令人担忧。建议那些仅淀粉样蛋白阳性的人，更普遍地说，大多数生物标志物阳性的认知正常个体，不应被标记为患有 AD。相反，他们应该被视为有患 AD 的风险。对于那些具有特定生物标志物模式的人来说，症状前 AD 的扩展被视为更好的诊断结构，表明它们接近于不久的将来症状的表达。