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

Disclosures

Age Ageing. 2019;48(2):174-177. 

In This Article

Clinical Creep

The framework's authors recognise that clinical adoption of their new criteria could fuel over-diagnosis and emphasise that the definitions are for research purposes only at the moment. However, research criteria and nomenclature do not, and arguably should not, exist in a separate space to clinical practice. These proposals will inevitably shift the disease boundary in the clinic. In doing so, they will provide a powerful impetus to the spread of biomarkers into diagnostic practice. Such changes are already occurring, under commercial pressure, despite the lack of validation and the absence of any evidence of improved outcomes. The definition of what constitutes an improved clinical outcome is also being stretched, with recent studies addressing the value of these investigations including such inconsequential outcomes as clinical trial referrals or additional tests.[8] We note that the UK National Institute for Health and Care Excellence has promoted use of CSF and imaging biomarker tests in its recent guidance on dementia diagnosis, which is intended to inform clinical practice.[9] When considering the risk of clinical creep, we should be aware that the proposed disease definitions will be, in practice, inapplicable in low income settings and probably also beyond the available resources in many higher income settings, leading to serious inconsistencies in practice.

The framework also has important implications for drug development and the pharmaceutical industry. Defining disease on the basis of biomarkers alone is a very large step towards the approval of treatments on the basis of effects on those biomarkers, rather than on the basis of demonstrable benefits to patients. The large and growing proportion of older adults in the population makes this a potentially lucrative market.

The authors of the framework envisage that additional biomarker domains will be incorporated into the model. The implication is that more and more asymptomatic people will be identified as having a neurodegenerative disease, with no requirement for the disease labels to be accompanied by either symptoms or a thorough understanding of prognosis or treatment implications. This is an alarming expansion of the concept of disease which may have far-reaching psychological, social, legal and financial consequences for individuals, consequences which are hard to study or to quantify.[10]

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