NIA-AA Research Framework: Towards a Biological Definition of Alzheimer’s Disease

17 In 2011 the National Institute on Aging and Alzheimer’s Association (NIA-AA) created 18 separate diagnostic recommendations for the preclinical, mild cognitive impairment, and 19 dementia stages of Alzheimers disease. Scientific progress in the interim led to an initiative by 20 the NIA-AA to update and unify the 2011 guidelines. This unifying update is labeled a “research 21 framework”, because its intended use is for observational and interventional research, not routine 22 clinical care. In the NIA AA research framework Alzheimer’s disease (AD) is defined by its 23 underlying pathologic processes which can be documented by post-mortem examination or in 24 vivo by biomarkers. The diagnosis is not based on the clinical consequences of the disease (i.e. 25 symptoms/signs) in this research framework which shifts the diagnosis of AD in living people 26 from a syndromal to a biological construct. The research framework focuses on the diagnosis of 27 AD with biomarkers in living persons. Biomarkers are grouped into those of β-amyloid 28 deposition, pathologic tau, and neurodegeneration. Two cognitive staging schemes are described: 29 a scheme employing 3 traditional syndromal categories and a 6 stage numeric scheme. We 30 envision that defining AD as a biological construct will enable a more accurate characterization 31 DRAFT – AS of September 19, 2017 DO NOT REPRODUCE and understanding of the sequence of events that lead to cognitive impairment as well as the 32 multi factorial etiology of dementia. This approach also will enable a more precise approach to 33 interventional trials where specific pathways can be targeted in the disease process and in the 34 appropriate people. Importantly, the validity of this construct should be determined in more 35 diverse populations. 36