Personalized risk for clinical progression in cognitively normal subjects-the ABIDE project
Open accessAbstract
BACKGROUND: Biomarkers such as cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) have predictive value for progression to dementia in patients with mild cognitive impairment (MCI). The pre-dementia stage takes far longer, and the interpretation of biomarker findings is particular relevant for individuals who present at a memory clinic, but are deemed cognitively normal. The objective of the current study is to construct biomarker-based prognostic models for personalized risk of clinical progression in cognitively normal individuals presenting at a memory clinic. METHODS: We included 481 individuals with subjective cognitive decline (SCD) from the Amsterdam Dementia Cohort. Prognostic models were developed by Cox regression with patient characteristics, MRI, and/or CSF biomarkers to predict clinical progression to MCI or dementia. We estimated 5- and 3-year individualized risks based on patient-specific values. External validation was performed on Alzheimer's Disease Neuroimaging Initiative (ADNI) and an European dataset. RESULTS: Based on demographics only (Harrell's C = 0.70), 5- and 3-year progression risks varied from 6% [3-11] and 4% [2-8] (age 55, MMSE 30) to 38% [29-49] and 28% [21-37] (age 70, MMSE 27). Normal CSF biomarkers strongly decreased progression probabilities (Harrell's C = 0.82). By contrast, abnormal CSF markedly increased risk (5 years, 96% [56-100]; 3 years, 89% [44-99]). The CSF model could reclassify 58% of the individuals with an "intermediate" risk (35-65%) based on the demographic model. MRI measures were not retained in the models. CONCLUSION: The current study takes the first steps in a personalized approach for cognitively normal individuals by providing biomarker-based prognostic models.
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Individuals with subjective cognitive decline with biomarker-based evidence of Alzheimer's disease are at higher risk for developing cognitive decline.
“Individuals with SCD with a biomarker-based evidence of AD are at higher risk for developing cognitive decline [5–7].”
From Psychotherapeutic interventions in individuals at risk for Alzheimer’s dementia: a systematic review (2022) · cites this paper as [6]
Current individualised prediction models do not work sufficiently well in cognitively unimpaired people compared with people who are in the prodromal stage of Alzheimer's disease.
“current individualised prediction models do not work sufficiently well in cognitively unimpaired people compared with people who are in the prodromal stage of Alzheimer’s disease.62”
From Clinical diagnosis of Alzheimer’s disease: Recommendations of the International Working Group (2021) · cites this paper as [62]
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- Authors
- Initiative, F. T. A. D. N., van Maurik, I. S., Slot, R. E. R., Verfaillie, S. C. J., Zwan, M. D., Bouwman, F. H., Prins, N. D., Teunissen, C. E., Scheltens, P., Barkhof, F., Wattjes, M. P., Molinuevo, J. L., Rami, L., Wolfsgruber, S., Peters, O., Jessen, F., Berkhof, J., & van der Flier, W. M.
- Affiliations
- Amsterdam Neuroscience (NL)
- University of Bonn (DE)
- University of Cologne (DE)
- Amsterdam University Medical Centers (NL)
- ORCID
- Venue
- Alzheimer's Research & Therapy
- Published
- 2019-04-16
- Volume
- 11
- Issue
- 1
- Pages
- 33-33
- ISSN
- 1758-9193 (ISSN-L)
- PMC
- PMC6466790
- OpenAlex
- W2938385363
- Cited by
- 47
- References
- 53
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 7 · 2023: 6 · 2022: 5 · 2021: 11 · 2020: 8 · 2019: 2
- FWCI
- 5.18
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Alzheimer s Research & Therapy (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UCL Discovery (University College London) (submittedVersion)
- DZNE Pub (submittedVersion, cc-by)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- LSH-TKI (LSHM16025)
- 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
- cognitively normal individuals, subjective cognitive decline, dementia risk prediction, cerebrospinal fluid biomarkers, MRI biomarkers, prognostic model, pre-dementia, memory clinic patients, Alzheimer's disease
- MeSH terms
- Aged, Brain, Dementia, Female, Humans, Male, Middle Aged, Risk Factors, Biomarkers, Disease Progression, Precision Medicine, Cognitive Dysfunction
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