The rationale behind the IWG criteria for Alzheimer's disease

Abstract

AbstractBackgroundThe development of in‐vivo biomarkers has moved the diagnosis of Alzheimer’s disease from the dementia stage towards the prodromal stage, and has introduced the potential for preclinical diagnosis (ie, before symptom onset). These developments are relevant for the testing of potential therapies for secondary prevention of Alzheimer’s disease.MethodReview of the literatureResultIn 2018, the US National Institute on Aging and the Alzheimer’s Association proposed a purely biological definition of Alzheimer’s disease that relies on biomarkers. Although the intended use of this framework was for research purposes, it has engendered debate and challenges regarding its use in everyday clinical practice, at least for the supposely preclinical stage of the disease. For instance, cognitively unimpaired individuals can have biomarker evidence of both amyloid β and tau pathology but will often not develop clinical manifestations in their lifetime. This was previously underlined by neuropathologists who indicate a consensus to disentangle the clinic‐pathological term ‘Alzheimer’s disease’ from the presence of Alzheimer lesions in the brain in their ‘NIA‐AA guidelines for the neuropathological assessment of Alzheimer’s disease’. Furthermore, a positive Alzheimer’s disease pattern of biomarkers can be observed in other brain diseases in which Alzheimer’s disease pathology is present as a comorbidity.ConclusionIn line with these observations, the International Working Group recommend that Alzheimer’s disease diagnosis be restricted to people who have positive biomarkers together with specific Alzheimer’s disease phenotypes, whereas biomarker‐positive cognitively unimpaired individuals should be considered only at‐risk for progression to Alzheimer’s disease.