MRI and cerebrospinal fluid biomarkers for predicting progression to Alzheimer's disease in patients with mild cognitive impairment: a diagnostic accuracy study
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Objectives: To assess the incremental value of MRI and cerebrospinal fluid (CSF) analysis after a short memory test for predicting progression to Alzheimer's disease from a pragmatic clinical perspective. Design: Diagnostic accuracy study in a multicentre prospective cohort study. Setting: Alzheimer Disease Neuroimaging Initiative participants with complete data on neuropsychological assessment, MRI of the brain and CSF analysis. Participants: Patients with mild cognitive impairment (MCI; n=181) were included. Mean follow-up was 38.9 months (range 5.5–75.9). Main outcome measures: Diagnostic accuracy of individual instruments and incremental value of entorhinal cortex volume on MRI and p-τ/Aβ ration in CSF after administration of Rey's Auditory Verbal Learning Memory Test are calculated and expressed as the ‘Net Reclassification Improvement’ (NRI), which is the change in the percentage of individuals that are correctly diagnosed as Alzheimer or non-Alzheimer case. Results: Tested in isolation, a short memory test, MRI and CSF all substantially contribute to the differentiation of those MCI patients who remain stable during follow-up from those who progress to develop Alzheimer's disease. The memory test, MRI and CSF improved the diagnostic classification by 21% (95% CI 15.1 to 26.9), 22.1% (95% CI 16.1 to 28.1) and 18.8% (95% CI 13.1 to 24.5), respectively. After administration of a short memory test, however, the NRI of MRI is +1.1% (95% CI 0.1 to 3.9) and of CSF is −2.2% (95% CI −5.6 to −0.6). Conclusions: After administration of a brief test of memory, MRI or CSF do not substantially affect diagnostic accuracy for predicting progression to Alzheimer's disease in patients with MCI. The NRI is an intuitive and easy to interpret measure for evaluation of potential added value of new diagnostic instruments in daily clinical practice.
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A number of studies have suggested that CSF markers in combination with neuroimaging and neuropsychological tools add to the accuracy of AD diagnosis.
“A number of studies have suggested that CSF markers in combination with neuroimaging and neuropsychological tools add to the accuracy of AD diagnosis (Richard et al., 2013; Schuff et al., 2009; Vemuri et al., 2010).”
From T1rho MRI and CSF biomarkers in diagnosis of Alzheimer's disease (2015) · cites this paper as Richard et al., 2013
The Discussion (Implications for clinical practice and research; page not provided) concludes that neither MRI nor CSF analysis importantly increases diagnostic accuracy for progression to AD in patients with mild cognitive impairment when a brief memory test is administered first. That is contrary to attributing an accuracy gain from combining these tools to this study. (LLM, conf=0.88)
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- Authors
- Richard, E., Schmand, B. A., Eikelenboom, P., & Van Gool, W. A.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Corresponding author
- Richard, Edo
- Venue
- BMJ Open
- Publisher
- BMJ
- Published
- 2013-06
- Volume
- 3
- Issue
- 6
- Pages
- e002541
- ISSN
- 2044-6055 (ISSN-L)
- PMC
- PMC3686215
- OpenAlex
- W2107634703
- Cited by
- 84
- References
- 5
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 4 · 2022: 2 · 2021: 4 · 2020: 8 · 2019: 10 · 2018: 8 · 2017: 9 · 2016: 6 · 2015: 14 · 2014: 7 · 2013: 4
- FWCI
- 7.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- BMJ Open (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- UvA-DARE (University of Amsterdam) (publishedVersion, other-oa)
- Pure Amsterdam UMC (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Foundation for the National Institutes of Health (P30AG010129, K01 AG030514, U01AG024904, Grant U01 AG024904, AG024904)
- Alzheimer's Association (AG010129, U01 AG024904)
- Dana Foundation (P30 AG010129, K01 AG030514, U01 AG024904)
- Bristol-Myers Squibb (U01 AG024904, AG024904)
- Eli Lilly and Company (U01 AG024904, AG024904)
- Pfizer (AG024904, U01 AG024904)
- AstraZeneca
- Biogen (U01 AG024904, AG024904)
- F. Hoffmann-La Roche (AG024904, U01 AG024904)
- Medpace (U01 AG024904)
- Meso Scale Diagnostics (U01 AG024904, AG024904)
- Synarc (U01 AG024904, P30 AG010129, K01 AG030514)
- Alzheimer's Disease Neuroimaging Initiative (U01AG024904, AG024904, P30 AG010129, K01 AG030514)
- Amorfix Life Sciences
- BioClinica (U01 AG024904, AG024904)
- Novartis Pharmaceuticals Corporation (U01 AG024904, AG024904)
- Northern California Institute for Research and Education (U01 AG024904, K01 AG030514, P30 AG010129)
- Bayer HealthCare
- Eisai (U01 AG024904, AG024904)
- Servier (AG024904, U01 AG024904)
- National Institutes of Health (3u01ag024904-10s2, U01-AG024904, Grant U01 AG024904, AG010129, AG024904)
- Genentech (AG024904, U01 AG024904)
- University of California, Los Angeles
- University of California, San Diego
- Canadian Institutes of Health Research (U01 AG024904, K01 AG030514, P30 AG010129)
- National Institute on Aging (U01-AG-024904, P30AG010129, AG 024904, K01AG030514, AG010129)
- National Institute of Biomedical Imaging and Bioengineering (U01 AG024904, AG024904)
- 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
- Alzheimer's disease, mild cognitive impairment, progression prediction, cerebrospinal fluid biomarkers, Rey Auditory Verbal Learning Test, magnetic resonance imaging, diagnostic accuracy, net reclassification improvement, incremental diagnostic value
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