Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory Clinic Patients in a Prospective Cohort

Ron L. H. Handels*, Manuela A. Joore, Stephanie J. B. Vos, Pauline Aalten, Inez H. G. B. Ramakers, Marcel Olde Rikkert, Philip Scheltens, Willemijn J. Jansen, Pieter-Jelle Visser, Bart M. N. van Berckel, Peter van Domburg, Machiel Smid, Erik Hoff, Jan Hoogmoed, Femke Bouwman, Jurgen Claassen, Albert F. G. Leentjens, Claire A. G. Wolfs, Johan L. Severens, Frans R. J. Verhey

*Corresponding author for this work

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Background: Limited information is available on short-term prognosis of Alzheimer's disease (AD) biomarkers in cerebrospinal fluid (CSF) in addition to routine diagnostic workup. Objective: This study aims to investigate the added prognostic value of AD CSF biomarkers. Methods: In a prospective cohort study, clinical experts predicted cognitive and functional symptoms in 114 memory clinic patients by assessing comprehensive routine diagnostic test information (patient history, and physical, neurological, psychiatric, neuropsychological, and MRI examinations), without and with CSF biomarkers. The reference standard was the 'observed clinically relevant decline' using baseline and 1- and 2-year follow-up information. Results: Decline over a 2-year period was observed in 51% of all participants (3% in SMC, 48% in MCI, 90% in mild dementia). In the total sample, the accuracy of predicted decline did not differ significantly between routine assessment without (79% correctly predicted) and with (74% correctly predicted) CSF biomarkers. Subgroup analyses revealed 25 (83%) correct predictions in SMC, 30 (68%) in MCI, and 35 (88%) in dementia without the use of CSF; and 21 (70%), 27 (61%), and 36 (90%), respectively, with the use of CSF in addition to the routine assessment. Conclusion: AD CSF biomarkers did not increase accuracy of 2-year prognosis of cognitive and functional decline when added to routine diagnostic workup. This suggests that the standard diagnostic workup without CSF biomarkers allows fairly accurate predictions for the short-term course of symptoms. Routine AD biomarkers in CSF have limited prognostic value over 2 years in persons with a suspected cognitive disorder.
Original languageEnglish
Pages (from-to)875-885
JournalJournal of Alzheimer's Disease
Issue number3
Publication statusPublished - 2016


  • Alzheimer's disease
  • cerebrospinal fluid
  • memory disorders
  • mild cognitive impairment
  • prognosis
  • sensitivity and specificity

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