. An Operational Approach to NIA-AA Criteria for Preclinical Alzheimer’s Disease. Ann Neurol. 2011 Oct 1;


Objective: A workgroup commissioned by the Alzheimer’s Association (AA) and the National Institute on Aging (NIA) recently published research criteria for preclinical Alzheimer’s disease (AD). We performed a preliminary assessment of these guidelines.

Methods: We employed Pittsburgh compound B positron emission tomography (PET) imaging as our biomarker of cerebral amyloidosis and 18fluorodeoxyglucose PET imaging and hippocampal volume as biomarkers of neurodegeneration. A group of 42 clinically diagnosed AD subjects was used to create imaging biomarker cut-points. A group of 450 cognitively normal (CN) subjects from a population based sample was used to develop cognitive cut-points and to assess population frequencies of the different preclinical AD stages using different cut-point criteria.

Results: The new criteria subdivide the preclinical phase of AD into stages 1-3. To classify our CN subjects, two additional categories were needed. Stage 0 denotes subjects with normal AD biomarkers and no evidence of subtle cognitive impairment. Suspected Non-AD Pathophysiology (SNAP) denotes subjects with normal amyloid PET imaging, but abnormal neurodegeneration biomarker studies. At fixed cut-points corresponding to 90% sensitivity for diagnosing AD and the 10th percentile of CN cognitive scores, 43% of our sample was classified as stage 0; 16% stage 1; 12 % stage 2; 3% stage 3; and 23% SNAP.

Interpretation: This cross-sectional evaluation of the NIA-AA criteria for preclinical AD indicates that the 1-3 staging criteria coupled with stage 0 and SNAP categories classify 97% of CN subjects from a population-based sample, leaving just 3% unclassified. Future longitudinal validation of the criteria will be important.


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  1. Overall, I think this is an important step forward in validating the preclinical staging framework in a well-characterized sample drawn from a community-dwelling cohort. The designation of additional categories is useful to provide a classification scheme for all "normals," but I think it will be important to learn more about the SNAP group in terms of other pathologies (cerebrovascular, other neurodegenerative diseases, hippocampal sclerosis, etc). Ultimately, the question is whether the Stage 1-3 preclinical framework is useful in predicting likelihood of decline towards MCI and AD dementia, for use in secondary prevention and very early intervention trials.

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