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

Article type: Research Article

Authors: Handels, Ron L.H.^{a; b; *} | Joore, Manuela A.^{b; c} | Vos, Stephanie J.B.^a | Aalten, Pauline^a | Ramakers, Inez H.G.B.^a | Rikkert, Marcel Olde^d | Scheltens, Philip^e | Jansen, Willemijn J.^a | Visser, Pieter-Jelle^{a; e} | van Berckel, Bart M.N.^e | van Domburg, Peter^f | Smid, Machiel^g | Hoff, Erik^h | Hoogmoed, Jan^{i; j} | Bouwman, Femke^e | Claassen, Jurgen^d | Leentjens, Albert F.G.^a | Wolfs, Claire A.G.^a | Severens, Johan L.^k | Verhey, Frans R.J.^a

Affiliations: [a] Alzheimer Centre Limburg, Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, the Netherlands | [b] CAPHRI School for Public Health and Primary Care, Faculty of Health Medicine and Life Sciences, Department of Health Organization, Policy and Economics, Maastricht University, Maastricht, the Netherlands | [c] Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht, the Netherlands | [d] Radboudumc Alzheimer Centre, Department of Geriatrics, Donders Centre for Brain, Cognition and Behavior, Radboud University Medical Centre, Nijmegen, The Netherlands | [e] Department of Neurology and Alzheimer Centre, VU University Medical Centre, Amsterdam, The Netherlands | [f] Department of Neurology, Zuyderland Medical Centre, Sittard, The Netherlands. | [g] Department of Geriatrics, Zuyderland Medical Centre, Sittard, The Netherlands. | [h] Department of Neurology, Zuyderland Medical Centre, Heerlen, The Netherlands | [i] Department of Geriatrics, Laurentius Hospital Roermond, Roermond, The Netherlands | [j] Department of Geriatrics, St. Jans Gasthuis Weert, Weert, The Netherlands | [k] Institute of Health Policy and Management, Erasmus University Rotterdam, Rotterdam, The Netherlands

Correspondence: [*] Correspondence to: Ron L.H. Handels, Department of Psychiatry and Neuropsychology, Maastricht University/Alzheimer Centre Limburg, P.O. Box 616, 6200 MD Maastricht, The Netherlands. Tel.: +31 43 3881041; E-mail: ron.handels@maastrichtuniversity.nl.

Abstract: 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.

Keywords: Alzheimer’s disease, cerebrospinal fluid, memory disorders, mild cognitive impairment, prognosis, sensitivity and specificity

DOI: 10.3233/JAD-151120

Journal: Journal of Alzheimer's Disease, vol. 52, no. 3, pp. 875-885, 2016