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Biomarker testing in MCI patients-deciding who to test
Ingrid S van Maurik1,2, Hanneke F M Rhodius-Meester3,4, Charlotte E Teunissen5
1Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, VU University Medical Center, Vrije Universiteit Amsterdam, Amsterdam UMC, De Boelelaan 1118, 1081 HZ, Amsterdam, The Netherlands. i.vanmaurik@amsterdamumc.nl.
Background:
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.
Methods:
MCI 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.
Results:
The 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.
Interpretation:
CSF 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.
