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An operational approach to National Institute on Aging–Alzheimer's Association criteria for preclinical Alzheimer disease
Author(s) -
Jack 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.
Publication year - 2012
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.22628
Subject(s) - biomarker , alzheimer's disease , medicine , population , neurodegeneration , dementia , positron emission tomography , disease , stage (stratigraphy) , cognitive decline , oncology , psychology , pathology , nuclear medicine , paleontology , biochemistry , chemistry , environmental health , biology
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 ANN NEUROL 2012;