Title | An operational approach to National Institute on Aging-Alzheimer's Association criteria for preclinical Alzheimer disease. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Jack, CR, Knopman, DS, Weigand, SD, Wiste, HJ, Vemuri, P, Lowe, V, Kantarci, K, Gunter, JL, Senjem, ML, Ivnik, RJ, Roberts, RO, Rocca, WA, Boeve, BF, Petersen, RC |
Journal | Ann Neurol |
Volume | 71 |
Issue | 6 |
Pagination | 765-75 |
Date Published | 2012 Jun |
ISSN | 1531-8249 |
Keywords | Aged, Aged, 80 and over, Alzheimer Disease, Aniline Compounds, Biomarkers, Brain, Cognition Disorders, Disease Progression, Female, Fluorodeoxyglucose F18, Humans, Longitudinal Studies, Male, Mental Status Schedule, National Institute on Aging (U.S.), Neuropsychological Tests, Positron-Emission Tomography, Thiazoles, United States |
Abstract | 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. |
DOI | 10.1002/ana.22628 |
Alternate Journal | Ann. Neurol. |
PubMed ID | 22488240 |
PubMed Central ID | PMC3586223 |
Grant List | C06 RR018898 / RR / NCRR NIH HHS / United States C06 RR018898 / RR / NCRR NIH HHS / United States P50 AG016574 / AG / NIA NIH HHS / United States P50 AG16574 / AG / NIA NIH HHS / United States R01 AG011378 / AG / NIA NIH HHS / United States R01 AG041851 / AG / NIA NIH HHS / United States R01 AG11378 / AG / NIA NIH HHS / United States U01 AG006786 / AG / NIA NIH HHS / United States U01 AG006786 / AG / NIA NIH HHS / United States |