Commentary
Video
Educating the Clinical Community on Differences in Alzheimer Diagnostic Criteria: Clifford Jack, MD
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The neuroradiologist at Mayo Clinic provided clinical insights on the controversy with two recently published Alzheimer criteria, with one diagnosing the disease based on biomarkers alone vs clinical symptoms. [WATCH TIME: 4 minutes]
WATCH TIME: 4 minutes
"The logical flaw falls because the IWG uses a non-specific entity, clinical symptoms, to define Alzheimer’s disease. Symptoms have never been... a lot of things can cause symptoms. Alzheimer disease is one of them, but so can LATE (limbic-predominant age-related TDP-43 encephalopathy) and so can microinfarcts. And LATE is not Alzheimer disease. Microinfarcts are not Alzheimer disease."
In 2024, the clinical community saw two new diagnostic criteria published for Alzheimer's disease (AD): one by the Alzheimer’s Association (AA) and the other by the International Working Group (IWG). While the understanding of the underpinnings of the disease has improved, these two criteria differ in ways that could impact clinical care and the diagnosis of the disease.
The criteria by the AA define AD as a biological process that begins with the appearance of AD neuropathologic change while individuals are asymptomatic. To establish a diagnosis of AD according to this definition, an abnormal core 1 biomarker result is needed, while later-changing core 2 biomarkers may provide more prognostic information. In addition, the AA introduced an integrated biological and clinical staging scheme that accommodates the fact that common copathologies, cognitive reserve, and resistance may modify relationships between clinical and biological AD stages. The IWG criteria offer an alternative definitional view of AD as a clinical-biological construct, recommending that those who are amyloid-positive only, and more generally, biomarker-positive cognitively normal individuals, should not be labeled as having AD.1,2
The differences between these two criteria were discussed in a presentation by Clifford Jack, MD, at the 2025 AD/PD International Conference on Alzheimer’s and Parkinson’s Diseases, held April 1-5 in Vienna, Austria. Jack, a neuroradiologist at Mayo Clinic and lead author of the 2024 AA criteria, spoke on the controversy in the diagnostic criteria for AD, stressing that the AA’s approach offers a more precise and scientifically accurate framework. Above all, Jack highlighted the need for the clinical community to be on the same page with AD diagnosis, emphasizing that it is not unique to AD that diseases are defined by biology and staged by biology plus clinical symptoms.
Click here for more coverage of AD/PD 2025.
