Alzheimer's Association Update for January 2013

In 2011, workgroups established by the National Institute on Aging and the Alzheimer’s Association (NIA-AA) published four papers in which they proposed revising the 25-year-old criteria for diagnosing Alzheimer’s disease (AD)[1–4]. The aim of the new criteria revised guidelines was to improve diagnostic accuracy, particularly during the early phases of disease. These papers have generated a flurry of discussion in the Alzheimer’s community as researchers, clinicians, and pharmaceutical companies consider the implications of implementing revised criteria in clinical practice, research, and drug development. Among those weighing in were participants in the Alzheimer’s Association’s Research Roundtable, a consortium of scientists from the pharmaceutical, biotechnology, imaging, and cognitive testing industries. Along with scientists from academia, the National Institutes of Health, the U.S. Food and Drug Administration, and the AA, the Research Roundtable met on October 1 and 2, 2012, in Washington, DC, to address concerns, identify research gaps, and recommend next steps toward validating and implementing the new criteria. Chaired by Robert Dean, MD, PhD, of Eli Lilly & Co, and David Knopman, MD, of the Mayo Clinic, the meeting considered not only the NIA-AA guidelines, but also those of the International Working Group (IWG), which published research criteria in 2007. “Both of these efforts reflect a struggle between what we know vs what we assume about the linkages between the pathology and the clinical manifestations of the disease,” said Dean in his opening remarks. Moreover, both groups understand that the flood of new data being generated demands regular reconsideration and revision of the criteria. “Clearly we can’t wait another 25 years to do that,” said Dean. Recognizing that AD occurs on a continuum, the NIA-AA workgroups designated three phases of the disease: preclinical AD, mild cognitive impairment resulting from AD, and dementia resulting from AD. Both the NIA-AA and IWG incorporate biomarker evidence into their criteria to enable more precise diagnosis. For example, based on biomarker evidence, dementia may be classified as probably, possibly, or unlikely to be of the Alzheimer’s type. The new diagnostic criteria may have their greatest effect in the clinical trials arena, including upcoming prevention trials in presymptomatic AD. Although harmonization of the NIA-AA and IWG criteria would be beneficial, most Roundtable participants agreed that the differences between the two are minimal and will continue to evolve as further studies in representative, heterogeneous populations converge on a definitive, common set of criteria. Widespread acceptance of biomarkers for use in research and clinical settings, and in clinical trials, will require standardization of methods for conducting biomarker tests as well as establishment of cutpoints that distinguish positive biomarker signals from negative signals. International consortia organized by the AA, the Coalition Against Major Diseases, and other organizations have alreadymade substantial headway in this area. Roundtable participants ended the meeting with a sense of optimism tempered by realization of the challenges that lie ahead as the field moves toward identifying individuals at the earliest possible stage of the disease. Clinical criteria combined with biomarkers appear to increase confidence in diagnosis, yet the question remains as to how specific the criteria need to be—or, in other words, how good is good enough? A more detailed report of this meeting will appear in a future issue of Alzheimer’s & Dementia.