Jack CR, Knopman DS, Weigand SD, Wiste HJ, Vemuri P, Lowe V, Kantarci K, Gunter JL, Senjem ML, Petersen RC.
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.