Criteria for the clinical diagnosis of Alzheimer’s Disease (AD) were established by a National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and the Alzheimer’s Disease and Related Disorders Association (ADRDA) workgroup in 1984 . These criteria were universally adopted, have been extremely useful, and have survived intact without modification for over a quarter of a century. In the intervening 27 years, however, important advances in our understanding of AD, in our ability to detect the pathophysiological process of AD, and changes in conceptualization regarding the clinical spectrum of the disease have occurred.
By 2009 broad consensus existed throughout academia and industry that the criteria should be revised to incorporate scientific advances in the field. In response to this imperative the National Institute on Aging (NIA) and the Alzheimer’s Association (AA) sponsored a series of advisory round table meetings in 2009 whose purpose was to establish a process for revising diagnostic and research criteria for the continuum of AD. These advisory meetings included members from academia and industry with an international representation. The consensus from the advisory meetings was that three separate work groups should be formed under the auspices of the NIA and AA. One work group was assigned the task of formulating diagnostic criteria for the dementia phase of AD. A second was asked to focus on diagnostic criteria for the symptomatic pre-dementia phase of AD. The third workgroup was asked to propose a research agenda for the asymptomatic, preclinical phase of AD. Individuals were selected to serve in these work groups, by the NIA and the AA, with the objective of having balanced expertise and international representation from academia and industry. From early to mid 2010 the three work groups met via conference call and in person (as feasible). Each formulated a set of recommendations. These recommendations were presented in a symposium at the 2010 ICAD meeting. They were posted on the Alzheimer’s Association website for a period of public comment over the summer of 2010. Comments received during this period, from the website and other venues, were given to the individual workgroups and incorporated into revisions of each document in the fall of 2010. Lastly, a subcommittee representing individuals from each of the workgroups was asked to review the recommendations, particularly with regard to the approach to biomarkers, and a final round of revisions was made to each document in the late fall of 2010 for purposes of harmonizing the discussion of biomarkers. The final documents were submitted simultaneously in early 2011 to the NIA for review and to the journal for peer review.
The charge to the workgroups was very specific and did not include several related topics. First, it was decided at the outset that a fourth, separate workgroup would be organized to develop revised pathological criteria. Thus, while neuropathologists were represented on each of the three workgroups, the recommendations of the three workgroups do not include a detailed discussion of neuropathologic criteria. The deliberations of the neuropathology workgroup are expected to appear later in 2011. Second, the workgroups were asked to outline future issues that need to be addressed by the research community as a whole, but the specifics for how this will be done, including potential timelines, are not included in these recommendations. This is particularly relevant to the discussion of biomarkers in each of the three documents. There was a consensus among the members of the workgroups that it was premature to define specific cut-points denoting normal vs abnormal values for the biomarkers discussed, and that much work remains to be done with regard to uniform assessment and standardization of biomarkers. Third, the workgroups were specifically asked to focus on the spectrum of AD, and not to try to revise criteria for other neurodegenerative diseases or cerebrovascular dementias. Thus, the set of recommendations presented here only refer to other disorders as they relate to differential diagnosis of AD.