Cited by 602Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCancer-related cognitive impairment studies

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

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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.·2012·Annals of Neurology

DOI 10.1002/ana.22628PMC PMC3586223

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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.

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Authors: Jack, C. R., Knopman, D. S., Weigand, S. D., Wiste, H. J., Vemuri, P., Lowe, V., Kantarci, K., Gunter, J. L., Senjem, M. L., Ivnik, R. J., Roberts, R. O., Rocca, W. A., Boeve, B. F., & Petersen, R. C.
Affiliations: Mayo Clinic (US)
Corresponding author: Jack, Clifford R.
ORCID: Jack, Clifford R.
Knopman, David S.
Weigand, Stephen D.
Wiste, Heather J.
Vemuri, Prashanthi
Lowe, Val
Kantarci, Kejal
Gunter, Jeffrey L.
Senjem, Matthew L.
Rocca, Walter A.
Boeve, Bradley F.
Petersen, Ronald C.
Venue: Annals of Neurology
Publisher: Wiley
Published: 2012-04-09
Volume: 71
Issue: 6
Pages: 765-775
ISSN: 0364-5134 (ISSN-L)
1531-8249
DOI: 10.1002/ana.22628
PMC: PMC3586223
OpenAlex: W2044429455
Cited by: 602
References: 71
Citations by year: 2026: 14 · 2025: 23 · 2024: 21 · 2023: 28 · 2022: 29 · 2021: 40 · 2020: 33 · 2019: 40 · 2018: 44 · 2017: 60 · 2016: 80 · 2015: 65 · 2014: 63 · 2013: 51 · 2012: 10
FWCI: 27.52
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Annals of Neurology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Mayo Clinic
Mayo Foundation for Medical Education and Research
National Institute on Aging (R01AG11378, P50‐AG16574, U01AG006786, R01AG011378, R01AG041851, P50AG016574)
National Center for Research Resources (C06RR018898)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Oncology › Cancer-related cognitive impairment studies
Keywords: preclinical Alzheimer's disease, NIA-AA criteria, Pittsburgh compound B PET, cerebral amyloidosis, FDG-PET, hippocampal volume, neurodegeneration biomarkers, cognitively normal older adults, diagnostic classification
MeSH terms: Aged, Aged, 80 and over, Alzheimer Disease, Aniline Compounds, Brain, Cognition Disorders, Female, Humans, Longitudinal Studies, Male, Mental Status Schedule, Neuropsychological Tests, Thiazoles, United States, Biomarkers, Disease Progression, Fluorodeoxyglucose F18, Positron-Emission Tomography, National Institute on Aging (U.S.)

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

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