Rethinking Alzheimer Diagnosis and Disease Staging: Clifford Jack, MD

WATCH TIME: 4 minutes

"Alzheimer disease is a chronic disease—if you wait until symptoms appear, the brain damage is already extensive and irreversible. We need to think ahead."

In 2024, 2 major frameworks for Alzheimer disease (AD) diagnosis–the Alzheimer’s Association (AA) and the International Working Group (IWG)–offered updated criteria, each reflecting differing approaches to defining the disease. The AA’s criteria emphasized a biological definition, classifying AD strictly based on the presence of amyloid (A), tau (T), and neurodegeneration (N) biomarkers, regardless of clinical symptoms. In contrast, the IWG 2024 criteria maintained a clinical-biological approach, requiring not only biomarker confirmation of AD pathology but also the presence of specific cognitive symptoms, particularly amnestic syndromes, for diagnosis.

At the 2025 AD/PD International Conference on Alzheimer’s and Parkinson’s Diseases, held April 1-5 in Vienna, Austria, Clifford Jack, MD, lead author of the AA’s published criteria, led a session on the differences between the 2 criterias. Jack, a neuroradiologist at Mayo Clinic, sat down with NeurologyLive® during the meeting to discuss ways the clinical community can come together to address some of the controversies between these criterias. In the interview, he noted that historical trials using symptom-based enrollment led to significant diagnostic error rates, reinforcing the need for biomarker-based confirmation.

Despite supporting the scientific validity of identifying preclinical AD pathology, Jack stressed that asymptomatic individuals should not yet be tested–given the absence of an approved treatment for this population. However, he urged clinicians to begin to think of AD as a chronic disease, with a likely future where early detection and preclinical intervention will become standard.

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REFERENCES
1. Jack CR, Andrews JS, Beach TG, et al. Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup. Alzheimers & Dement. 2024;20(8):5143-5169. doi:10.1002/alz.13859
2. Dubois B, Villain N, Schneider L, et al. Alzheimer Disease as a Clinical-Biological Construct—An International Working Group Recommendation. JAMA Neurol. 2024;81(12):1304-1311. doi:10.1001/jamaneurol.2024.3770