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IWG Proposes New Clinical-Biological Definition for Diagnosing Alzheimer’s Disease

NextEdge Admin

07 Nov 2024

2 min 43 sec

JAMA Neurology,The International Working Group (IWG)

The International Working Group (IWG) has proposed a new definition of Alzheimer's disease, emphasizing that cognitive deficits must be present alongside brain amyloid to make a diagnosis. This approach, presented at the Clinical Trials on Alzheimer's Disease (CTAD) meeting and published in *JAMA Neurology*, contrasts with a recent Alzheimer's Association (AA) workgroup’s biological definition, which allows diagnosis based solely on positive biomarkers, even if cognitive symptoms are absent. The IWG definition highlights Alzheimer's as a "clinical-biological entity," requiring both cognitive symptoms and biomarkers for diagnosis.

Howard Feldman, MD, from UC San Diego, explained that the IWG's definition permits an early Alzheimer's diagnosis when mild cognitive signs are observed. The IWG framework addresses concerns that diagnosing cognitively normal individuals with only positive biomarkers, as proposed by the AA, could lead to false positives. The AA's biological definition reflects practices in cancer and heart disease diagnosis, but IWG members argue this may wrongly label asymptomatic individuals as having Alzheimer’s. Bruno Dubois, MD, a lead IWG member, warned that many biomarker-positive individuals might never develop symptomatic Alzheimer's.

The IWG categorizes individuals based on symptoms and biomarker status: those with cognitive impairment and positive biomarkers have Alzheimer's disease, cognitively normal individuals with amyloid biomarkers are "asymptomatic at risk," and those with genetic risk factors or specific biomarkers are "presymptomatic." Ronald Petersen, MD, from the Mayo Clinic, noted that while the AA recommends against testing asymptomatic individuals outside research, the growing availability of biomarker tests raises ethical concerns. The IWG thus maintains that Alzheimer's should remain a diagnosis grounded in both clinical symptoms and pathology, rather than solely biomarker positivity, preserving the focus on risk versus disease.