Mild cognitive impairment due to Alzheimer disease in the community

Ronald Carl Petersen, Paul Aisen, Bradley F Boeve, Yonas Endale Geda, Robert J. Ivnik, David S Knopman, Michelle M Mielke, Vernon S. Pankratz, Rosebud O Roberts, Walter A Rocca, Stephen Weigand, Michael Weiner, Heather Wiste, Clifford R Jr. Jack

Research output: Contribution to journalArticle

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Abstract

Objective The newly proposed National Institute on Aging-Alzheimer's Association (NIA-AA) criteria for mild cognitive impairment (MCI) due to Alzheimer disease (AD) suggest a combination of clinical features and biomarker measures, but their performance in the community is not known. Methods The Mayo Clinic Study of Aging (MCSA) is a population-based longitudinal study of nondemented subjects in Olmsted County, Minnesota. A sample of 154 MCI subjects from the MCSA was compared to a sample of 58 amnestic MCI subjects from the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI-1) to assess the applicability of the criteria in both settings and to assess their outcomes. Results Fourteen percent of MCSA and 16% of ADNI-1 of subjects were biomarker negative. In addition, 14% of MCSA and 12% of ADNI-1 subjects had evidence for amyloid deposition only, whereas 43% of MCSA and 55% of ADNI-1 subjects had evidence for amyloid deposition plus neurodegeneration (magnetic resonance imaging atrophy, fluorodeoxyglucose positron emission tomography hypometabolism, or both). However, a considerable number of subjects had biomarkers inconsistent with the proposed AD model; for example, 29% of MCSA subjects and 17% of ADNI-1 subjects had evidence for neurodegeneration without amyloid deposition. These subjects may not be on an AD pathway. Neurodegeneration appears to be a key factor in predicting progression relative to amyloid deposition alone. Interpretation The NIA-AA criteria apply to most MCI subjects in both the community and clinical trials settings; however, a sizeable proportion of subjects had conflicting biomarkers, which may be very important and need to be explored.

Original languageEnglish (US)
Pages (from-to)199-208
Number of pages10
JournalAnnals of Neurology
Volume74
Issue number2
DOIs
StatePublished - Aug 2013

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Alzheimer Disease
Neuroimaging
Amyloid
National Institute on Aging (U.S.)
Biomarkers
Positron-Emission Tomography
Atrophy
Longitudinal Studies
Cognitive Dysfunction
Magnetic Resonance Imaging
Clinical Trials
Population

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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Mild cognitive impairment due to Alzheimer disease in the community. / Petersen, Ronald Carl; Aisen, Paul; Boeve, Bradley F; Geda, Yonas Endale; Ivnik, Robert J.; Knopman, David S; Mielke, Michelle M; Pankratz, Vernon S.; Roberts, Rosebud O; Rocca, Walter A; Weigand, Stephen; Weiner, Michael; Wiste, Heather; Jack, Clifford R Jr.

In: Annals of Neurology, Vol. 74, No. 2, 08.2013, p. 199-208.

Research output: Contribution to journalArticle

Petersen, Ronald Carl ; Aisen, Paul ; Boeve, Bradley F ; Geda, Yonas Endale ; Ivnik, Robert J. ; Knopman, David S ; Mielke, Michelle M ; Pankratz, Vernon S. ; Roberts, Rosebud O ; Rocca, Walter A ; Weigand, Stephen ; Weiner, Michael ; Wiste, Heather ; Jack, Clifford R Jr. / Mild cognitive impairment due to Alzheimer disease in the community. In: Annals of Neurology. 2013 ; Vol. 74, No. 2. pp. 199-208.
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AU - Petersen, Ronald Carl

AU - Aisen, Paul

AU - Boeve, Bradley F

AU - Geda, Yonas Endale

AU - Ivnik, Robert J.

AU - Knopman, David S

AU - Mielke, Michelle M

AU - Pankratz, Vernon S.

AU - Roberts, Rosebud O

AU - Rocca, Walter A

AU - Weigand, Stephen

AU - Weiner, Michael

AU - Wiste, Heather

AU - Jack, Clifford R Jr.

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N2 - Objective The newly proposed National Institute on Aging-Alzheimer's Association (NIA-AA) criteria for mild cognitive impairment (MCI) due to Alzheimer disease (AD) suggest a combination of clinical features and biomarker measures, but their performance in the community is not known. Methods The Mayo Clinic Study of Aging (MCSA) is a population-based longitudinal study of nondemented subjects in Olmsted County, Minnesota. A sample of 154 MCI subjects from the MCSA was compared to a sample of 58 amnestic MCI subjects from the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI-1) to assess the applicability of the criteria in both settings and to assess their outcomes. Results Fourteen percent of MCSA and 16% of ADNI-1 of subjects were biomarker negative. In addition, 14% of MCSA and 12% of ADNI-1 subjects had evidence for amyloid deposition only, whereas 43% of MCSA and 55% of ADNI-1 subjects had evidence for amyloid deposition plus neurodegeneration (magnetic resonance imaging atrophy, fluorodeoxyglucose positron emission tomography hypometabolism, or both). However, a considerable number of subjects had biomarkers inconsistent with the proposed AD model; for example, 29% of MCSA subjects and 17% of ADNI-1 subjects had evidence for neurodegeneration without amyloid deposition. These subjects may not be on an AD pathway. Neurodegeneration appears to be a key factor in predicting progression relative to amyloid deposition alone. Interpretation The NIA-AA criteria apply to most MCI subjects in both the community and clinical trials settings; however, a sizeable proportion of subjects had conflicting biomarkers, which may be very important and need to be explored.

AB - Objective The newly proposed National Institute on Aging-Alzheimer's Association (NIA-AA) criteria for mild cognitive impairment (MCI) due to Alzheimer disease (AD) suggest a combination of clinical features and biomarker measures, but their performance in the community is not known. Methods The Mayo Clinic Study of Aging (MCSA) is a population-based longitudinal study of nondemented subjects in Olmsted County, Minnesota. A sample of 154 MCI subjects from the MCSA was compared to a sample of 58 amnestic MCI subjects from the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI-1) to assess the applicability of the criteria in both settings and to assess their outcomes. Results Fourteen percent of MCSA and 16% of ADNI-1 of subjects were biomarker negative. In addition, 14% of MCSA and 12% of ADNI-1 subjects had evidence for amyloid deposition only, whereas 43% of MCSA and 55% of ADNI-1 subjects had evidence for amyloid deposition plus neurodegeneration (magnetic resonance imaging atrophy, fluorodeoxyglucose positron emission tomography hypometabolism, or both). However, a considerable number of subjects had biomarkers inconsistent with the proposed AD model; for example, 29% of MCSA subjects and 17% of ADNI-1 subjects had evidence for neurodegeneration without amyloid deposition. These subjects may not be on an AD pathway. Neurodegeneration appears to be a key factor in predicting progression relative to amyloid deposition alone. Interpretation The NIA-AA criteria apply to most MCI subjects in both the community and clinical trials settings; however, a sizeable proportion of subjects had conflicting biomarkers, which may be very important and need to be explored.

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