The ethics of biomarker-based preclinical diagnosis of Alzheimer’s disease

Abstract

In older adults who are developing Alzheimer-typical pathology but do not experience any symptoms—a condition termed “preclinical” Alzheimer’s disease—the individual prognostic value of current biomarkers is low. Only a minority of those who have positive findings on biomarkers in the cerebrospinal fluid or upon brain imaging experience cognitive decline within 3–5 years. On the other hand, the majority of people who have negative biomarker results remain cognitively intact. This may be expected in research settings where alternative causes of cognitive impairment are infrequent. The main reasons for the poor predictive performance of biomarkers in asymptomatic individuals are the dynamic nature of the assessments with abnormality evolving over time and the large interindividual variability of the threshold for clinical manifestation. We do not recommend biomarker assessment and disclosure of biomarker results to asymptomatic individuals outside of research protocols or clinical trials at this point in time. More needs to be learned about the interplay between biomarkers, risk factors, and protective factors. Also, studies are required with extended follow-up intervals on less selected participant groups to determine the long-term predictive potential of biomarkers in presymptomatic Alzheimer’s disease.