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Mild cognitive impairment due to Alzheimer disease in the community
Open accessAbstract
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. Ann Neurol 2013;74:199–208
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“The rate of cognitive decline is significantly greater for cognitively impaired and CU individuals who have abnormalities in both an amyloid biomarker and a second biomarker type (which could be CSF T-tau or P-tau, atrophy, or hypometabolism) in comparison to individuals who have neither or only one of these biomarker abnormalities [30–35,39,40,42–45].”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [39]
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“However, the combination of an abnormal MRI, CSF T-tau, or FDG PET study with an abnormal amyloid biomarker provides much more powerful prediction of future cognitive decline [30–35,39,40,42–45] than an abnormal amyloid study alone.”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [39]
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“studies assessing biomarkers for Alzheimer's disease with PET scans have reported that about half of people with MCI have Alzheimer's-related brain changes.230,231”
From 2023 Alzheimer's disease facts and figures (2023) · cites this paper as [230]
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“Meanwhile, studies assessing biomarkers for Alzheimer's disease with PET scans have reported that about half of people with MCI have Alzheimer's‐related brain changes.”
From 2024 Alzheimer's disease facts and figures (2024) · cites this paper as [246]
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“MCI with negative biomarkers versus 1 or more AD pathology biomarkers (ie, AD pattern in CSF, high amyloid load in amyloid PET) or biomarkers of neurodegeneration (eg, AD pattern on structural MRI or fluorodeoxyglucose [FDG]-PET; high CSF tau and phospho-tau levels) has a 2 to 3 relative risk of progression to dementia (8% vs 17%-22% per year 33 ).”
From The Alzheimer’s Disease Clinical Spectrum (2019) · cites this paper as [33]
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Metadata
- Authors
- Petersen, R. C., Aisen, P., Boeve, B. F., Geda, Y. E., Ivnik, R. J., Knopman, D. S., Mielke, M., Pankratz, V. S., Roberts, R., Rocca, W. A., Weigand, S., Weiner, M., Wiste, H., & Jack, C. R.
- Affiliations
- Mayo Clinic (US)
- University of California San Diego (US)
- University of California, San Francisco (US)
- Corresponding author
- Petersen, Ronald C.
- ORCID
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2013-08
- Volume
- 74
- Issue
- 2
- Pages
- 199-208
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC3804562
- OpenAlex
- W1559001474
- Cited by
- 265
- References
- 51
- Citations by year
- 2026: 11 · 2025: 11 · 2024: 15 · 2023: 13 · 2022: 16 · 2021: 21 · 2020: 18 · 2019: 31 · 2018: 25 · 2017: 26 · 2016: 28 · 2015: 25 · 2014: 18 · 2013: 7
- FWCI
- 18.42
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (5u01ag024904-10)
- Canadian Institutes of Health Research
- National Institute on Aging (U01-AG-024904, R01AG034676, P30AG010129, U01AG006786, K01AG030514, R01AG011378, R01AG041851, P50AG016574)
- 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
- mild cognitive impairment, Alzheimer's disease, NIA-AA criteria, amyloid deposition, neurodegeneration, biomarkers, amyloid PET, FDG-PET hypometabolism, brain atrophy, conversion to dementia, Mayo Clinic Study of Aging, non-demented elderly
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Amyloid, Female, Humans, Male, Neuropsychological Tests, Random Allocation, Residence Characteristics, Biomarkers, Cognitive Dysfunction
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