International Working Group Recommends Against Diagnosing Alzheimer Disease Based on Biomarkers Alone

According to a Special Communication from the International Working Group (IWG), published in JAMA Neurology, most people who are cognitively normal and have biomarkers of Alzheimer disease (AD), including those who are amyloid-positive, should not be diagnosed with AD. The new recommendations are a response to the Alzheimer’s Association’s recently published “Revised Criteria for Diagnosis and Staging of Alzheimer's Disease,” which propose that AD be defined based on biological evidence alone. The IWG’s recommendations were also presented at the 17th annual Clinical Trials on Alzheimer’s Disease (CTAD) conference.

According to the authors, disclosing a diagnosis of AD to cognitively normal people with only core 1 AD biomarkers represents a problematic, purely biological definition of disease, whereas according to recent literature, the majority of people with biomarkers of AD do not become symptomatic over a proximate timespan. Instead, the authors propose the use of 3 terms, which are intended to integrate clinical and biological factors of disease.

• At Risk of Alzheimer Disease refers to cognitively normal individuals who are at increased lifetime risk of AD due to a biomarker profile associated with brain amyloidosis and/or tauopathy or a positive phosphorylated tau biomarker.
• Presymptomatic Alzheimer Disease refers to cognitively normal individuals with specific biomarker profiles with a very high or almost deterministic lifetime risk of AD, such as people with Down syndrome.
• Alzheimer Disease refers to people with cognitive impairment and specific clinical phenotypes and cerebrospinal fluid (CSF) or PET AD biomarkers, including people with mild cognitive impairment (MCI) and dementia.

The IWG recommends that biomarker testing for cognitively normal individuals only be performed on the basis of evaluating, communicating, and reducing risk, and that biomarkers not be used to diagnose AD in those with normal cognition with or without complaints (eg, subjective cognitive decline).