Comparing predictors of conversion and decline in mild cognitive impairment
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Objective: A variety of measurements have been individually linked to decline in mild cognitive impairment (MCI), but the identification of optimal markers for predicting disease progression remains unresolved. The goal of this study was to evaluate the prognostic ability of genetic, CSF, neuroimaging, and cognitive measurements obtained in the same participants. Methods:APOE ε4 allele frequency, CSF proteins (Aβ1-42, total tau, hyperphosphorylated tau [p-tau181p]), glucose metabolism (FDG-PET), hippocampal volume, and episodic memory performance were evaluated at baseline in patients with amnestic MCI (n = 85), using data from a large multisite study (Alzheimer9s Disease Neuroimaging Initiative). Patients were classified as normal or abnormal on each predictor variable based on externally derived cutoffs, and then variables were evaluated as predictors of subsequent conversion to Alzheimer disease (AD) and cognitive decline (Alzheimer9s Disease Assessment Scale–Cognitive Subscale) during a variable follow-up period (1.9 ± 0.4 years). Results: Patients with MCI converted to AD at an annual rate of 17.2%. Subjects with MCI who had abnormal results on both FDG-PET and episodic memory were 11.7 times more likely to convert to AD than subjects who had normal results on both measures (p ≤ 0.02). In addition, the CSF ratio p-tau181p/Aβ1-42 (β = 1.10 ± 0.53; p = 0.04) and, marginally, FDG-PET predicted cognitive decline. Conclusions: Baseline FDG-PET and episodic memory predict conversion to AD, whereas p-tau181p/Aβ1-42 and, marginally, FDG-PET predict longitudinal cognitive decline. Complementary information provided by these biomarkers may aid in future selection of patients for clinical trials or identification of patients likely to benefit from a therapeutic intervention.
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Most works support the hypothesis that amnestic subtype of MCI is more likely to subsequently convert to AD, although this is still debated.
“Most of works support the hypothesis that amnestic subtype of MCI is more likely to subsequently convert to AD [43], although this is still a debated issue [44].”
From Atrophy of presubiculum and subiculum is the earliest hippocampal anatomical marker of Alzheimer's disease (2015) · cites this paper as [43]
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Self-citationLimited agreement between biomarkers of neuronal injury at different stages of Alzheimer's disease
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- Authors
- Landau, S. M., Harvey, D., Madison, C. M., Reiman, E. M., Foster, N. L., Aisen, P. S., Petersen, R. C., Shaw, L. M., Trojanowski, J. Q., Jack, C. R., Weiner, M. W., & Jagust, W. J.
- Affiliations
- Mayo Clinic (US)
- From the Helen Wills Neuroscience Institute (S.M.L., C.M.M., W.J.J.), University of California, Berkeley; Department of Public Health Sciences (D.H.), School of Medicine, University of California, Davis; Banner Alzheimer's Institute (E.M.R.), Phoenix, AZ; Department of Neurology (N.L.F.), University of Utah, Salt Lake City; Department of Neurosciences (P.S.A.), University of California, San Diego; Behavioral Neurology (R.C.P.), Mayo Clinic College of Medicine, Rochester, MN; Department of Pathology...
- ORCID
- Venue
- Neurology
- Published
- 2010-07-20
- Volume
- 75
- Issue
- 3
- Pages
- 230-238
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC2906178
- OpenAlex
- W1969787718
- Cited by
- 616
- References
- 40
- Citations by year
- 2026: 10 · 2025: 18 · 2024: 27 · 2023: 17 · 2022: 22 · 2021: 30 · 2020: 35 · 2019: 39 · 2018: 32 · 2017: 40 · 2016: 51 · 2015: 47 · 2014: 53 · 2013: 69 · 2012: 57
- FWCI
- 41.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Donald W. Reynolds Foundation
- Larry L. Hillblom Foundation
- Amgen
- Bristol-Myers Squibb (U01 AG024904, AG024904)
- Eli Lilly and Company (U01 AG024904, AG024904)
- Pfizer (AG024904, U01 AG024904)
- AstraZeneca
- GlaxoSmithKline
- Baxter International
- Ben B. and Iris M. Margolis Foundation
- University of Pennsylvania (P50 NS053488)
- Alzheimer's Disease Neuroimaging Initiative (U01AG024904, AG024904)
- Takeda Pharmaceuticals U.S.A.
- University of Alabama at Birmingham
- University of Alabama
- Myriad Genetics
- University of Oxford
- Elan (U01 AG024904)
- Eisai (U01 AG024904, AG024904)
- National Institutes of Health (5u01ag024904-10, AG11378, U01-AG024904, NIA PO1 AG 17586-10, NINDS P50 NS053488-02, AG 17586, NS053488, AG024904, AG10483)
- Genentech (AG024904, U01 AG024904)
- U.S. Public Health Service (R01 G10897)
- Avid Radiopharmaceuticals
- National Institute on Aging (AG027984, U01-AG-024904, AG 10483, P30AG010129, R01AG027984, U01 AG024904-01, AG-06786, 10124, RC1AG035427, P01 AG 17586-10, R01AG030048, AG 024904, AG 16574, UO1AG029213-01, P30AG036468, U01AG006786, K01AG030514, R01AG029672, 1 U01 AG 024904-05, P30AG010124, P01AG009215, P30 AG 10124-18, P01AG017586, U01AG010483, AG17586, AG031581, R01AG011378, 17586, 1 U01 AG24904, 1P01 AG-19724-07, U01AG029213, R01AG031581, R01AG027859, AG027859, AG-11378, R01AG022394, R01AG016381, RC2AG036535, U19AG010483, P01 AG 09215-20, P01AG012435, P01AG019724, P50AG023501, P50AG016574, R01AG031252)
- National Institute of Neurological Disorders and Stroke (NS053488, RL1NS062412, P50NS053488, RC2NS069368, R01NS031966, T32NS007222)
- National Institute of Biomedical Imaging and Bioengineering (R01EB000768)
- National Center for Research Resources (P41RR023953, R24 RR021992)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
- Keywords
- mild cognitive impairment, cognitive decline, prognostic factors, FDG-PET, episodic memory, phosphorylated tau, amyloid-beta, cerebrospinal fluid biomarkers, hippocampal volume, APOE ε4, Alzheimer's disease
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Cognition Disorders, Female, Follow-Up Studies, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Memory Disorders, Middle Aged, Neuropsychological Tests, Peptide Fragments, Predictive Value of Tests, ROC Curve, Time Factors, Amyloid beta-Peptides, tau Proteins, Disease Progression, Statistics, Nonparametric, Fluorodeoxyglucose F18, Positron-Emission Tomography, Apolipoprotein E4
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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