Van Maurik, IS;
Slot, RER;
Verfaillie, SCJ;
Zwan, MD;
Bouwman, FH;
Prins, ND;
Teunissen, CE;
... Alzheimer’s Disease Neuroimaging Initiative; + view all
(2019)
Personalized risk for clinical progression in cognitively normal subjects—the ABIDE project.
Alzheimer's Research & Therapy
, 11
, Article 33. 10.1186/s13195-019-0487-y.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Personalized risk for clinical progression in cognitively normal subjects—the ABIDE project |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1186/s13195-019-0487-y |
| Publisher version: | https://doi.org/10.1186/s13195-019-0487-y |
| Language: | English |
| Additional information: | Copyright © The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
| Keywords: | Biomarkers, Progression, Cerebrospinal fluid, Magnetic resonance imaging |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Brain Repair and Rehabilitation |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10073998 |
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