%0 Journal Article %J Ann Neurol %D 2012 %T An operational approach to National Institute on Aging-Alzheimer's Association criteria for preclinical Alzheimer disease. %A Jack, Clifford R %A Knopman, David S %A Weigand, Stephen D %A Wiste, Heather J %A Vemuri, Prashanthi %A Lowe, Val %A Kantarci, Kejal %A Gunter, Jeffrey L %A Senjem, Matthew L %A Ivnik, Robert J %A Roberts, Rosebud O %A Rocca, Walter A %A Boeve, Bradley F %A Petersen, Ronald C %K Aged %K Aged, 80 and over %K Alzheimer Disease %K Aniline Compounds %K Biomarkers %K Brain %K Cognition Disorders %K Disease Progression %K Female %K Fluorodeoxyglucose F18 %K Humans %K Longitudinal Studies %K Male %K Mental Status Schedule %K National Institute on Aging (U.S.) %K Neuropsychological Tests %K Positron-Emission Tomography %K Thiazoles %K United States %X

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 (18) fluorodeoxyglucose 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.

%B Ann Neurol %V 71 %P 765-75 %8 2012 Jun %G eng %N 6 %1 http://www.ncbi.nlm.nih.gov/pubmed/22488240?dopt=Abstract %R 10.1002/ana.22628