Accurate risk estimation of β‐amyloid positivity to identify prodromal Alzheimer's disease: Cross‐validation study of practical algorithms
Open accessAbstract
Introduction: The aim was to create readily available algorithms that estimate the individual risk of β‐amyloid (Aβ) positivity. Methods: The algorithms were tested in BioFINDER (n = 391, subjective cognitive decline or mild cognitive impairment) and validated in Alzheimer's Disease Neuroimaging Initiative (n = 661, subjective cognitive decline or mild cognitive impairment). The examined predictors of Aβ status were demographics; cognitive tests; white matter lesions; apolipoprotein E (APOE); and plasma Aβ 42/Aβ 40, tau, and neurofilament light. Results: Aβ status was accurately estimated in BioFINDER using age, 10‐word delayed recall or Mini–Mental State Examination, and APOE (area under the receiver operating characteristics curve = 0.81 [0.77–0.85] to 0.83 [0.79–0.87]). When validated, the models performed almost identical in Alzheimer's Disease Neuroimaging Initiative (area under the receiver operating characteristics curve = 0.80–0.82) and within different age, subjective cognitive decline, and mild cognitive impairment populations. Plasma Aβ 42/Aβ 40 improved the models slightly. Discussion: The algorithms are implemented on http://amyloidrisk.com where the individual probability of being Aβ positive can be calculated. This is useful in the workup of prodromal Alzheimer's disease and can reduce the number needed to screen in Alzheimer's disease trials.
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Previous research attempted to develop algorithms combining multiple factors and showed better and more robust performance in predicting Aβ positivity of Alzheimer's disease.
“Previous research attempted to develop algorithms combining multiple factors and showed better and more robust performance in predicting Aβ positivity of Alzheimer’s disease.”
From Integrated algorithm combining plasma biomarkers and cognitive assessments accurately predicts brain β-amyloid pathology (2023) · cites this paper as [13]
Refinements to clinical pretest probability estimates will probably further improve plasma biomarker diagnostic performance and interpretation.
“Fourth, refinements to the clinical pretest probability estimates (for example, through polygenetic risk scores58 or through basic algorithms incorporating age, APOE genotype and cognitive testing59) will probably further improve plasma biomarker diagnostic performance and interpretation.”
From Diagnosis of Alzheimer's disease using plasma biomarkers adjusted to clinical probability (2024) · cites this paper as [59]
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- Authors
- Palmqvist, S., Insel, P. S., Zetterberg, H., Blennow, K., Brix, B., Stomrud, E., Initiative, T. A. D. N., study, T. S. B., Mattsson, N., & Hansson, O.
- Affiliations
- Lund University (SE)
- Sahlgrenska University Hospital (SE)
- Euroimmun Medizinische Labordiagnostika (Germany) (DE)
- Corresponding author
- Palmqvist, Sebastian
- Hansson, Oskar
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2018-10-23
- Volume
- 15
- Issue
- 2
- Pages
- 194-204
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC6374284
- OpenAlex
- W2897862050
- Cited by
- 65
- References
- 54
- Citations by year
- 2026: 1 · 2025: 9 · 2024: 8 · 2023: 10 · 2022: 5 · 2021: 13 · 2020: 11 · 2019: 8
- FWCI
- 6.25
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- H2020 European Research Council
- Vetenskapsrådet
- Hjärnfonden
- National Institutes of Health (U01 AG024904)
- U.S. Department of Defense (W81XWH-12-2-0012)
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- 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
- prodromal Alzheimer's disease
- MeSH terms
- Aged, Algorithms, Alzheimer Disease, Apolipoproteins E, Female, Humans, Male, Predictive Value of Tests, Biomarkers, Amyloid beta-Peptides, Positron-Emission Tomography, Cognitive Dysfunction
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