Short-term clinical outcomes for stages of NIA-AA preclinical Alzheimer disease

David S Knopman, Clifford R Jr. Jack, H. J. Wiste, S. D. Weigand, Prashanthi D Vemuri, Val Lowe, Kejal M Kantarci, J. L. Gunter, M. L. Senjem, R. J. Ivnik, Rosebud O Roberts, Bradley F Boeve, Ronald Carl Petersen

Research output: Contribution to journalArticle

184 Citations (Scopus)

Abstract

Objective: Recommendations for the diagnosis of preclinical Alzheimer disease (AD) have been formulated by a workgroup of the National Institute on Aging and Alzheimer's Association. Three stages of preclinical AD were described. Stage 1 is characterized by abnormal levels of β-amyloid. Stage 2 represents abnormal levels of β-amyloid and evidence of brain neurodegeneration. Stage 3 includes the features of stage 2 plus subtle cognitive changes. Stage 0, not explicitly defined in the criteria, represents subjects with normal biomarkers and normal cognition. The ability of the recommended criteria to predict progression to cognitive impairment is the crux of their validity. Methods: Using previously developed operational definitions of the 3 stages of preclinical AD, we examined the outcomes of subjects from the Mayo Clinic Study of Aging diagnosed as cognitively normal who underwent brain MRI or [18F]fluorodeoxyglucose and Pittsburgh compound B PET, had global cognitive test scores, and were followed for at least 1 year. Results: Of the 296 initially normal subjects, 31 (10%) progressed to a diagnosis of mild cognitive impairment (MCI) or dementia (27 amnestic MCI, 2 nonamnestic MCI, and 2 non-AD dementias) within 1 year. The proportion of subjects who progressed to MCI or dementia increased with advancing stage (stage 0, 5%; stage 1, 11%; stage 2, 21%; stage 3, 43%; test for trend, p 0.001). Conclusions: Despite the short follow-up period, our operationalization of the new preclinical AD recommendations confirmed that advancing preclinical stage led to higher proportions of subjects who progressed to MCI or dementia.

Original languageEnglish (US)
Pages (from-to)1576-1582
Number of pages7
JournalNeurology
Volume78
Issue number20
DOIs
StatePublished - May 15 2012

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Alzheimer Disease
Dementia
Amyloid
National Institute on Aging (U.S.)
Aptitude
Fluorodeoxyglucose F18
Brain
Cognition
Cognitive Dysfunction
Alzheimer's Disease
Mild Cognitive Impairment
Biomarkers
Proportion

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

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Short-term clinical outcomes for stages of NIA-AA preclinical Alzheimer disease. / Knopman, David S; Jack, Clifford R Jr.; Wiste, H. J.; Weigand, S. D.; Vemuri, Prashanthi D; Lowe, Val; Kantarci, Kejal M; Gunter, J. L.; Senjem, M. L.; Ivnik, R. J.; Roberts, Rosebud O; Boeve, Bradley F; Petersen, Ronald Carl.

In: Neurology, Vol. 78, No. 20, 15.05.2012, p. 1576-1582.

Research output: Contribution to journalArticle

Knopman, David S ; Jack, Clifford R Jr. ; Wiste, H. J. ; Weigand, S. D. ; Vemuri, Prashanthi D ; Lowe, Val ; Kantarci, Kejal M ; Gunter, J. L. ; Senjem, M. L. ; Ivnik, R. J. ; Roberts, Rosebud O ; Boeve, Bradley F ; Petersen, Ronald Carl. / Short-term clinical outcomes for stages of NIA-AA preclinical Alzheimer disease. In: Neurology. 2012 ; Vol. 78, No. 20. pp. 1576-1582.
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AU - Jack, Clifford R Jr.

AU - Wiste, H. J.

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AU - Vemuri, Prashanthi D

AU - Lowe, Val

AU - Kantarci, Kejal M

AU - Gunter, J. L.

AU - Senjem, M. L.

AU - Ivnik, R. J.

AU - Roberts, Rosebud O

AU - Boeve, Bradley F

AU - Petersen, Ronald Carl

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N2 - Objective: Recommendations for the diagnosis of preclinical Alzheimer disease (AD) have been formulated by a workgroup of the National Institute on Aging and Alzheimer's Association. Three stages of preclinical AD were described. Stage 1 is characterized by abnormal levels of β-amyloid. Stage 2 represents abnormal levels of β-amyloid and evidence of brain neurodegeneration. Stage 3 includes the features of stage 2 plus subtle cognitive changes. Stage 0, not explicitly defined in the criteria, represents subjects with normal biomarkers and normal cognition. The ability of the recommended criteria to predict progression to cognitive impairment is the crux of their validity. Methods: Using previously developed operational definitions of the 3 stages of preclinical AD, we examined the outcomes of subjects from the Mayo Clinic Study of Aging diagnosed as cognitively normal who underwent brain MRI or [18F]fluorodeoxyglucose and Pittsburgh compound B PET, had global cognitive test scores, and were followed for at least 1 year. Results: Of the 296 initially normal subjects, 31 (10%) progressed to a diagnosis of mild cognitive impairment (MCI) or dementia (27 amnestic MCI, 2 nonamnestic MCI, and 2 non-AD dementias) within 1 year. The proportion of subjects who progressed to MCI or dementia increased with advancing stage (stage 0, 5%; stage 1, 11%; stage 2, 21%; stage 3, 43%; test for trend, p 0.001). Conclusions: Despite the short follow-up period, our operationalization of the new preclinical AD recommendations confirmed that advancing preclinical stage led to higher proportions of subjects who progressed to MCI or dementia.

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