Journal
ANNALS OF NEUROLOGY
Volume 74, Issue 2, Pages 199-208Publisher
WILEY
DOI: 10.1002/ana.23931
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Funding
- NIH National Institute on Aging [U01 AG006786, P50 AG016574, R01 AG034676, R01 AG011378, RO1 AG041851]
- Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program
- ADNI (NIH) [U01 AG024904]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- Canadian Institutes of Health Research
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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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