An operational approach to National Institute on Aging-Alzheimer's Association criteria for preclinical Alzheimer disease.
Jack, Clifford R. Jr MD 1,*; Knopman, David S. MD 2,3; Weigand, Stephen D. MS 4; Wiste, Heather J. BA 4; Vemuri, Prashanthi PhD 1; Lowe, Val MD 1; Kantarci, Kejal MD 1; Gunter, Jeffrey L. PhD 1; Senjem, Matthew L. MS 1; Ivnik, Robert J. PhD, LP 5; Roberts, Rosebud O. MBBCh 3,6; Rocca, Walter A. MD, MPH 2,6; Boeve, Bradley F. MD 2,7; Petersen, Ronald C. MD, PhD 2,3,6
[Article]
Annals of Neurology.
71(6):765-775, June 2012.
(Format: HTML, PDF)
Objective: 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.
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 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.
Results: 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.
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 only 3% unclassified. Future longitudinal validation of the criteria will be important ANN NEUROL 2012;
Copyright (C) 2012 John Wiley & Sons, Inc.