2018 NIA-AA Research Framework to Investigate the Alzheimer ’ s Disease Continuum 1 2 DRAFT 7-18-17 3 4 5 Clifford

17 In 2011 the National Institute on Aging and Alzheimer’s Association (NIA-AA) created 18 separate diagnostic recommendations for preclinical, mild cognitive impairment, and dementia 19 stages of Alzheimers disease. Scientific progress in the interim led to an initiative by the NIA20 AA to update and unify the 2011 guidelines. This unifying update is labeled a “research 21 framework”, because its intended use is observational and interventional research studies, not 22 routine clinical care. In the 2018 research framework Alzheimers disease is defined by its 23 underlying pathophysiologic processes which can be documented in vivo by biomarkers or by 24 post-mortem examination. Notably, the clinical consequences of the disease (i.e. 25 symptoms/signs) will no longer be required for diagnosis. The framework outlined here focuses 26 on the diagnosis of Alzheimer’s disease with biomarkers in living persons. Biomarkers are 27 grouped into those of β-amyloid deposition, tau pathology, and neurodegeneration. Three 28 cognitive staging schemes are described with different contexts of use envisioned for each: a 29 scheme employing 3 traditional syndromal categories, a 6 stage numeric scheme and staging 30 using continuous cognitive measures. We envision that this framework will help establish a 31