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June 2016

Cognitive Decline in Preclinical Stage 2 Alzheimer Disease and Implications for Prevention Trials

Author Affiliations
  • 1Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston
  • 2Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
JAMA Neurol. 2016;73(6):640-642. doi:10.1001/jamaneurol.2016.0281

In 2011, a National Institute on Aging−Alzheimer’s Association (NIA-AA) work group published criteria for classifying clinically normal older individuals into biomarker-defined stages of preclinical Alzheimer disease using measures of Aβ and neurodegeneration (ND).1 These staging criteria assume a trajectory that begins with aberrant Aβ accumulation, followed by tau-mediated ND and subsequent cognitive decline. Clinically normal individuals in stage 1 are Aβ+/ND−, stage 2 are Aβ+/ND+, and stage 3 are similarly Aβ+/ND+ but also show subtle cognitive impairment (Figure). These criteria have created a common rubric to advance the study of preclinical Alzheimer disease and to move the field toward early intervention, when disease-modifying therapies may be the most efficacious. Along these lines, secondary prevention trials are using biomarker data to recruit clinically normal older individuals in the preclinical stage of Alzheimer disease to test whether an anti-Aβ therapy may prevent or mitigate cognitive decline.2

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