An operational approach to National Institute on Aging-Alzheimer's Association criteria for preclinical Alzheimer disease

• Published in: Annals of neurology Vol. 71; no. 6; pp. 765 - 775
• Main Authors: Jack Jr, Clifford R., Knopman, David S., Weigand, Stephen D., Wiste, Heather J., Vemuri, Prashanthi, Lowe, Val, Kantarci, Kejal, Gunter, Jeffrey L., Senjem, Matthew L., Ivnik, Robert J., Roberts, Rosebud O., Rocca, Walter A., Boeve, Bradley F., Petersen, Ronald C.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.06.2012; Wiley-Liss; Wiley Subscription Services, Inc
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - diagnosis; Aniline Compounds - standards; Biological and medical sciences; Biomarkers; Brain - diagnostic imaging; Cognition Disorders - diagnosis; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Progression; Female; Fluorodeoxyglucose F18 - standards; Humans; Longitudinal Studies; Male; Medical sciences; Mental Status Schedule; National Institute on Aging (U.S.) - standards; Neurodegeneration; Neurology; Neuropsychological Tests; Positron-Emission Tomography; Thiazoles - standards; United States; Nervous system diseases; Senescence; Alzheimer disease; Central nervous system disease; Surgical approach; Degenerative disease; Asymptomatic; Cerebral disorder
• ISSN: 0364-5134; 1531-8249; 1531-8249
• DOI: 10.1002/ana.22628

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;