When Is Alzheimer's Not Dementia—Cochrane Commentary on the National Institute on Ageing and Alzheimer's Association Research Framework for Alzheimer's Disease

Jenny Mccleery; Leon Flicker; Edo Richard; Terence J. Quinn


Age Ageing. 2019;48(2):174-177. 

In This Article

How Good are the Biomarkers

Data validating the suggested biomarkers against the development of clinical dementia are still sparse. Where data are available, these are often confined to unrepresentative populations and fail to adhere to best methodological practice.[6] The predictive value of individual biomarkers in persons with cognitive complaints, is low and the added value over and above simple cognitive tests has not been unequivocally shown.[7] As explained in the framework paper itself, up to 60% of cognitively unimpaired people aged over 80 would be classified within the Alzheimer's spectrum proposed, yet many of them would never develop cognitive symptoms.

Even within the exclusive neuropathological framework there are validity issues. The chosen CSF and imaging markers are described as interchangeable but the agreement between them is far from perfect. The NIA-AA state that this apparent discrepancy reflects choice of cut-points used to define biomarker positivity and the properties of the different assays. However, the framework does not offer practical guidance on standardising the measurement processes or interpreting conflicting biomarker results. The anticipation is that results will inevitably converge over a longer timescale, but this entails a certain amount of wishful thinking.