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

Clifford R Jr. Jack, David S Knopman, Stephen D. Weigand, Heather J. Wiste, Prashanthi D Vemuri, Val Lowe, Kejal M Kantarci, Jeffrey L. Gunter, Matthew L. Senjem, Robert J. Ivnik, Rosebud O Roberts, Walter A Rocca, Bradley F Boeve, Ronald Carl Petersen

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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 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.

Original languageEnglish (US)
Pages (from-to)765-775
Number of pages11
JournalAnnals of Neurology
Volume71
Issue number6
DOIs
StatePublished - Jun 2012

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National Institute on Aging (U.S.)
Alzheimer Disease
Biomarkers
Positron-Emission Tomography
Population
Amyloid
Guidelines
Research

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

An operational approach to National Institute on Aging-Alzheimer's Association criteria for preclinical Alzheimer disease. / Jack, Clifford R Jr.; Knopman, David S; Weigand, Stephen D.; Wiste, Heather J.; Vemuri, Prashanthi D; Lowe, Val; Kantarci, Kejal M; Gunter, Jeffrey L.; Senjem, Matthew L.; Ivnik, Robert J.; Roberts, Rosebud O; Rocca, Walter A; Boeve, Bradley F; Petersen, Ronald Carl.

In: Annals of Neurology, Vol. 71, No. 6, 06.2012, p. 765-775.

Research output: Contribution to journalArticle

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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 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.",
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AU - Wiste, Heather J.

AU - Vemuri, Prashanthi D

AU - Lowe, Val

AU - Kantarci, Kejal M

AU - Gunter, Jeffrey L.

AU - Senjem, Matthew L.

AU - Ivnik, Robert J.

AU - Roberts, Rosebud O

AU - Rocca, Walter A

AU - Boeve, Bradley F

AU - Petersen, Ronald Carl

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