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

Abstract and Introduction


Early 2018 saw the release of new diagnostic guidance on Alzheimer's disease from the National Institute on Ageing and the Alzheimer's Association (NIA-AA). This proposed research framework represents a fundamental change in how we think about Alzheimer's disease, moving from diagnosis based on clinical features to diagnosis based solely on biomarkers. These recommendations are contentious and have important implications for patients, clinicians, policy makers and the pharmaceutical industry. In this commentary, we offer a summary of the NIA-AA research framework. We then focus on five key areas: divorcing neuropathology from the clinical syndrome; the emphasis placed on one dementia subtype; validity of available biomarkers; the changing meaning of the term 'Alzheimer's disease'; and the potential for a research framework to influence clinical practice.


In order to understand a concept and use it effectively, we first have to define it. Medical conceptualisation of the common form of dementia experienced by older people has seen many iterations. Initially labelled 'senile dementia', it was considered an inevitable consequence of ageing and was generally presumed to be due to cerebral atherosclerosis. By the mid-20th century, this dogma was shaken by the observations that many people with so-called senile dementia had post-mortem neuropathological changes similar to those described by Alois Alzheimer.[1] Since then, creating consensus on how to classify and identify common forms of dementia, including Alzheimer's disease dementia (AD), has proven challenging. Various criteria have been suggested and these continue to evolve as our knowledge of the condition increases. In 2012 the United States National Institute on Ageing and the Alzheimer's Association (NIA-AA) issued dementia diagnostic guidance that incorporated new technologies such as cerebrospinal fluid (CSF) biomarkers as an adjunct to the traditional tools of history taking and examination.[2] For the first time, a state of pre-clinical dementia was defined based solely on biomarker patterns suggestive of underlying disease, without the need for any discernible clinical symptoms.

In response to the exponential growth of biomarker research since the publication of the 2012 guidelines, the NIA-AA convened an international expert panel to further collate the evidence. The results, published in early 2018, were a set of new diagnostic guidance materials entitled 'A Research Framework: Towards a biological definition of Alzheimer's Disease'.[3] Although described as a 'framework' and for research only, the NIA-AA materials make a number of suggestions that fundamentally challenge our current understanding of AD.