An operational approach to National Institute on Aging–Alzheimer's Association criteria for preclinical Alzheimer disease
Article first published online: 9 APR 2012
Copyright © 2012 American Neurological Association
Annals of Neurology
Volume 71, Issue 6, pages 765–775, June 2012
How to Cite
Jack, C. R., Knopman, D. S., Weigand, S. D., Wiste, H. J., Vemuri, P., Lowe, V., Kantarci, K., Gunter, J. L., Senjem, M. L., Ivnik, R. J., Roberts, R. O., Rocca, W. A., Boeve, B. F. and Petersen, R. C. (2012), An operational approach to National Institute on Aging–Alzheimer's Association criteria for preclinical Alzheimer disease. Ann Neurol., 71: 765–775. doi: 10.1002/ana.22628
- Issue published online: 20 JUN 2012
- Article first published online: 9 APR 2012
- Accepted manuscript online: 12 SEP 2011 08:28AM EST
- Manuscript Accepted: 2 SEP 2011
- Manuscript Revised: 24 AUG 2011
- Manuscript Received: 6 JUL 2011
- NIH/National Institute on Aging. Grant Numbers: R01 AG11378, U01 AG006786, P50 AG16574, C06 RR018898
A workgroup commissioned by the Alzheimer's Association (AA) and the National Institute on Aging (NIA) recently published research criteria for preclinical Alzheimer disease (AD). We performed a preliminary assessment of these guidelines.
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 cutpoints. A group of 450 cognitively normal (CN) subjects from a population-based sample was used to develop cognitive cutpoints and to assess population frequencies of the different preclinical AD stages using different cutpoint criteria.
The new criteria subdivide the preclinical phase of AD into stages 1 to 3. To classify our CN subjects, 2 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 cutpoints 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.
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 only 3% unclassified. Future longitudinal validation of the criteria will be important ANN NEUROL 2012;