Changing definitions of disease: Transformations in the diagnostic criteria for Alzheimer's disease

Whether Alzheimer's disease (AD) should be defined by symptoms, biological processes, or both, is a matter of debate. We aim to reconstruct the motivations, aims, and content of consecutive versions of AD diagnostic criteria.

We systematically analyzed publications on AD diagnostic criteria between 1984 and 2024.

Early diagnosis and incorporating recent scientific findings are recurring aims for criteria revisions but aims and motivations for revising are often unclear or ambiguous and reflection on previous criteria is lacking. The subsequent criteria, except International Working Group (IWG) 2021/2024, consistently lower the threshold for diagnosing AD and increasingly focus on amyloid β and tau biomarkers.

Subsequent AD criteria show an increasing "biomarkerization," but it is often unclear what problems revised criteria should solve and how effective they are. To overcome these limitations, future revisions should evaluate the effectiveness and impacts of previous criteria, and define clear problems and aims.

Early diagnosis and incorporating scientific insights are recurring aims. The aims of new criteria are often not clearly articulated or ambiguous. The number of requirements for an AD diagnosis decreases over time. Consecutive criteria for research and clinical use did not result in clear terminology. The AD definition is increasingly narrowed to amyloid β and tau.