Dubois Bruno, Villain Nicolas, Schneider Lon, Fox Nick, Campbell Noll, Galasko Douglas, Kivipelto Miia, Jessen Frank, Hanseeuw Bernard, Boada Mercè, Barkhof Frederik, Nordberg Agneta, Froelich Lutz, Waldemar Gunhild, Frederiksen Kristian Steen, Padovani Alessandro, Planche Vincent, Rowe Christopher, Bejanin Alexandre, Ibanez Agustin, Cappa Stefano, Caramelli Paulo, Nitrini Ricardo, Allegri Ricardo, Slachevsky Andrea, de Souza Leonardo Cruz, Bozoki Andrea, Widera Eric, Blennow Kaj, Ritchie Craig, Agronin Marc, Lopera Francisco, Delano-Wood Lisa, Bombois Stéphanie, Levy Richard, Thambisetty Madhav, Georges Jean, Jones David T, Lavretsky Helen, Schott Jonathan, Gatchel Jennifer, Swantek Sandra, Newhouse Paul, Feldman Howard H, Frisoni Giovanni B
Département de Neurologie, Groupe Hospitalier Pitié-Salpêtrière, AP-HP Sorbonne Université, Institute of Memory and Alzheimer's Disease, Paris, France.
Sorbonne Université, INSERM U1127, CNRS 7225, Institut du Cerveau - ICM, FrontLab, Paris, France.
JAMA Neurol. 2024 Dec 1;81(12):1304-1311. doi: 10.1001/jamaneurol.2024.3770.
Since 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's 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.
To 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.
PubMed 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.
In 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.
The 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.
自2018年以来，基于生物标志物的研究结果，出现了将阿尔茨海默病（AD）定义为一种纯粹生物学实体的趋势。阿尔茨海默病协会（AA）对AD标准的最新修订进一步推动了这一方向。然而，对于将AD的纯粹生物学定义应用于临床、广大社会对AD的理解以及基于血液的生物标志物转化为临床实践的担忧促使国际工作组（IWG）更新了这些建议。
考虑修订后的AA标准，并提供一种将AD视为临床生物学构建体以供临床使用的替代性定义观点。2021年IWG诊断标准的建议进行了更新，以进一步阐述风险状态和症状前状态。
在PubMed上搜索2020年7月1日至2024年3月1日期间发表的文章，使用的检索词为“生物标志物”或“淀粉样蛋白”或“tau蛋白”或“神经退行性变”或“临床前”或“脑脊液”或“正电子发射断层扫描”或“血浆”以及“阿尔茨海默病”。还检索了相关文章的参考文献。
在新的AA诊断标准中，AD在临床上可定义为包括具有一种核心AD生物标志物的认知正常人群。然而，最近的文献表明，大多数生物标志物呈阳性的认知正常个体在近期内不会出现症状。在临床环境中，仅向具有一种核心AD生物标志物的认知正常人群披露AD诊断是该疾病纯粹生物学定义最具问题的影响。
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构建体的情况下诊断AD的方法是不合理的，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。建议仅淀粉样蛋白呈阳性的个体，更普遍地说，大多数生物标志物呈阳性的认知正常个体，不应被标记为患有AD。相反，应将他们视为有患AD的风险。对于具有特定生物标志物模式、表明他们在不久的将来接近症状表达的个体，症状前AD的扩展被视为一种更好的诊断构建体。
