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

Summary of the Guidance

The main thrust of the research framework is to change the definition of AD from a clinical syndrome to a disease identified by specific biological features alone. The justification for this change in emphasis is that the disease of Alzheimer's is characterised by neuropathological change of amyloid plaque and neurofibrillary tangle and that it is this biological disease, rather than symptoms, that should be the focus of research attention.

We now have a substantial body of longitudinal data showing detectable change in various proteins many years prior to clinical symptoms of AD. Based on these data, and since in-vivo neuropathological diagnosis is unlikely, the framework proposes that biomarkers are used as a proxy for the neuropathology of AD in living subjects. The biomarkers of choice are markers of amyloid deposition (A), markers of fibrillary tau (T) and markers of neurodegeneration (N). For each category both a CSF and a neuroimaging biomarker are suggested. An AD spectrum disease is defined by the presence of at least one positive amyloid (A) biomarker, while the other biomarkers help to 'stage' the pathological process. Thus, a series of biomarker profiles based on differing combinations of A, T and N are possible, akin to the tumour, node, metastasis (TNM) system used in oncology. Accompanying cognitive symptoms can be added to the ATN system, but are not mandated or indeed necessary for diagnosis.

The full NIA-AA research framework documents along with commentary and supporting materials are available open access online.[3]