Elsevier

The Lancet Neurology

Volume 6, Issue 8, August 2007, Pages 734-746
The Lancet Neurology

Position Paper
Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS–ADRDA criteria

https://doi.org/10.1016/S1474-4422(07)70178-3Get rights and content

Summary

The NINCDS–ADRDA and the DSM-IV-TR criteria for Alzheimer's disease (AD) are the prevailing diagnostic standards in research; however, they have now fallen behind the unprecedented growth of scientific knowledge. Distinctive and reliable biomarkers of AD are now available through structural MRI, molecular neuroimaging with PET, and cerebrospinal fluid analyses. This progress provides the impetus for our proposal of revised diagnostic criteria for AD. Our framework was developed to capture both the earliest stages, before full-blown dementia, as well as the full spectrum of the illness. These new criteria are centred on a clinical core of early and significant episodic memory impairment. They stipulate that there must also be at least one or more abnormal biomarkers among structural neuroimaging with MRI, molecular neuroimaging with PET, and cerebrospinal fluid analysis of amyloid β or tau proteins. The timeliness of these criteria is highlighted by the many drugs in development that are directed at changing pathogenesis, particularly at the production and clearance of amyloid β as well as at the hyperphosphorylation state of tau. Validation studies in existing and prospective cohorts are needed to advance these criteria and optimise their sensitivity, specificity, and accuracy.

Section snippets

Background

For research purposes, the diagnosis of Alzheimer's disease (AD) is based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV-TR)1 and the National Institute of Neurological Disorders and Stroke–Alzheimer Disease and Related Disorders (NINCDS–ADRDA) working group.2 These accepted criteria are fulfilled in a two-step diagnostic process where there is initial identification of a dementia syndrome and then the application of criteria based on the

The case for revising the research criteria for AD diagnosis

There are several factors that highlight the need to update the current research criteria for AD.

Objectives

An international working group was convened in 2005 to discuss the opportunity for developing a diagnostic framework for AD that would include the prodromal stages and the integration of biomarkers and to define the future goals and steps for the validation of such a framework. This paper provides the consensus recommendations of the working group and sets out the framework for revised research criteria for AD that would apply both in the early stages and across the full spectrum of the illness.

Methods

15 international dementia experts were invited by two of the authors (Dubois and Scheltens) to attend a satellite workshop at the Second Congress of the International Society for Vascular Behavioural and Cognitive Disorders (Vas-Cog) in Florence on June 9, 2005. The participants were each asked to present the evidence base of published literature around a range of topics including clinical, functional, neuropsychiatric and behavioural, cognitive, neuroimaging, neuropathology, and laboratory

Proposed diagnostic criteria for probable AD

The proposed framework for revised criteria for probable AD retains the designation of probable AD. It does not include a designation of possible AD because of the incompatibility of this definition with diagnostic criteria that are highly specific for AD. The framework addresses the disease presentation that is typical for AD. We exclude atypical presentations including focal cortical syndromes (primary progressive aphasia, visuospatial dysfunction) where an antemortem diagnosis would at best

Discussion

This working group has identified, by consensus, that new research criteria are timely, realistic, and feasible. Our proposed AD diagnostic framework (panel 2)139 is anchored around a core clinical phenotype supported by brain-structure abnormalities, molecular imaging impairment, biochemical changes, or genetic mutations associated with AD. The timeliness of these criteria is underscored by the many drugs in development that are directed at changing the disease pathogenesis through amyloid

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    These authors contributed equally to this work

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