Abstract

BackgroundWe aimed to derive an algorithm to define the optimal proportion of patients with mild cognitive impairment (MCI) in whom cerebrospinal fluid (CSF) testing is of added prognostic value.MethodsMCI patients were selected from the Amsterdam Dementia Cohort (n = 402). Three-year progression probabilities to dementia were predicted using previously published models with and without CSF data (amyloid-beta1-42 (Abeta), phosphorylated tau (p-tau)). We incrementally augmented the proportion of patients undergoing CSF, starting with the 10% patients with prognostic probabilities based on clinical data around the median (percentile 45–55), until all patients received CSF. The optimal proportion was defined as the proportion where the stepwise algorithm showed similar prognostic discrimination (Harrell’s C) and accuracy (three-year Brier scores) compared to CSF testing of all patients. We used the BioFINDER study (n = 221) for validation.ResultsThe optimal proportion of MCI patients to receive CSF testing selected by the stepwise approach was 50%. CSF testing in only this proportion improved the performance of the model with clinical data only from Harrell’s C = 0.60, Brier = 0.198 (Harrell’s C = 0.61, Brier = 0.197 if the information on magnetic resonance imaging was available) to Harrell’s C = 0.67 and Brier = 0.190, and performed similarly to a model in which all patients received CSF testing. Applying the stepwise approach in the BioFINDER study would again select half of the MCI patients and yielded robust results with respect to prognostic performance.InterpretationCSF biomarker testing adds prognostic value in half of the MCI patients. As such, we achieve a CSF saving recommendation while simultaneously retaining optimal prognostic accuracy.

Highlights

  • We aimed to derive an algorithm to define the optimal proportion of patients with mild cognitive impairment (MCI) in whom cerebrospinal fluid (CSF) testing is of added prognostic value

  • The discriminative performance of the stepwise model started to increase if 10% of the patients surrounding the median received CSF testing

  • We showed that CSF biomarker testing adds prognostic value to clinical information in half of the MCI patients

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Summary

Introduction

We aimed to derive an algorithm to define the optimal proportion of patients with mild cognitive impairment (MCI) in whom cerebrospinal fluid (CSF) testing is of added prognostic value. Determining the underlying cause of cognitive complaints is Maurik et al Alzheimer's Research & Therapy (2021) 13:14 this practice guideline, clinicians tend to implicitly steer against biomarker testing in MCI patients [6], even when multiple studies have shown the prognostic value of CSF biomarkers in MCI on a group level [7, 8]. We think that this suboptimal use of biomarkers in the clinic might be due to the lack of practical cost-efficient tools. We took as a starting point the notion that these same models could have additional value as a decision support tool, to aid clinicians in selecting patients for additional CSF biomarker testing

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