Background:

1. Background: Cerebrospinal fluid (CSF) biomarkers have been reported to be useful in dementia diagnosis. New revised research criteria for the diagnosis of AD suggests that magnetic resonance imaging, positron emission tomography or CSF biomarkers may provide supportive information. CSF tests are cheaper and more readily available than PET and less time consuming than MRI volumetry. CSF changes reflect AD pathology earlier than MRI volumetry. Thus, it could be particularly suitable for very early diagnosis. Not much is known about CSF use in clinical practice in Europe.In 2007 a task force on the current use of CSF biomarkers was set up under the auspices of the European Federation of Neurological Society’s (EFNS) scientific panel on dementia. Fig. 1 a 1b Results: Detailed reports from each country is shown in the table 1. CSF beta-amyloid, total tau and phosphorylated tau proteins are frequently evaluated in the majority of the countries (in 18 out of 23 countries). No major technical or ethical issues were found that would hamper the procedure’s ability to become routine in early and differential diagnostics of Alzheimer´s disease. Cut-off values for beta-amyloid (median 500, range 300-849 pg/ml), total tau (367; 195 – 450 pg/ml) and phosphorylated tau (60; 40-85 pg/ml) varied considerably among countries and even within some countries (fig. 2 a,b). Use of cerebrospinal fluid biomarkers in diagnosis of dementia across Europe EFNS Scientific panel on dementiaHort Jakub1, Bartos Ales2, 3, Pirttilä Tuula4 and Scheltens Philip51Memory Disorders Clinic, Dept. of Neurology, Charles University in Prague, Second Faculty of Medicine, University Hospital Motol, Prague, Czech Republic, 2Alzheimer Disease Center, Prague Psychiatric Center, Prague, Czech Republic, 3 Dept. of Neurology, Charles University in Prague, Third Faculty of Medicine, University Hospital Kralovske Vinohrady, Prague, Czech Republic, 4Dept. of Neurology, Kuopio University Hospital, Finland, 5Dept. Neurology/Alzheimer Center, VU University Medical Center, Amsterdam, The Netherlands Table 1 A survey questionnaire on CSF biomarkers in Europe In your country, do you use CSF biomarkers in establishing a diagnosis of Alzheimer´s disease? For clinical purposes For research purposes For both We don´t use it and don´t intend to introduce it We don´t use it, but would like to introduce it If yes, is the examination reimbursed by health system providers?  yes  no Which tests do you use? Innogenetics Aethena  other, please specify.................................... How many laboratories in your country have experience with this procedure? One central laboratory More – please specify................................. Is spinal tap used in your country as: an outpatient procedure  a procedure deserving inpatient hospitalization Do you have any specific ethical commitee consideration for spinal tap in patients with dementia?  no  yes, please specify...................................... We perform spinal tap in patients with Mild cognitive impairment in mild dementia  in moderate dementia  in severe dementia  we use it for differential diagnosis of the other dementias Normative values of CSF biomarkers  weuse our own norms  we have adopted norms from the publication of other research groups Which norms do you use for: Amyloid beta, please specify ............................pg/ml Total tau protein, please specify........................pg/ml Phosphorylated tau protein, please specify....................pg/ml Please state your cut off values If there are norms in your country, are these widely accepted throughout the country or does each laboratory have its own norms? One set of norms, not published One set of norms, published in a national or international journal Each laboratory has its own norms How did you get the norms? all the controls have a neuropsychological examination and CT/MRI? control group is cognitively intact which was proven by an extensive neuropsychological testing, please specify....................................................................... Do you assess any other markers in CSF?  No Yes Please specify................................................................... • Methods: • We analyzed data from a survey on the use of CSF biomarkers in the diagnosis of dementia across Europe using a questionnaire which was filled out by representatives of the 25 member countries of the European Federation of Neurological Societies (EFNS) (fig. 1a,b). Fig. 2 a 2 b Conclusions: • CSF analysis of beta-amyloid, tau and phosphorylated tau is frequently used in Europe. However, the use of various cut off values seriously hampers comparability and yields a potential threat to an interpretation and balanced use in clinical practice. We recommend that each laboratory establishes normative data and that multi-centered studies should be organized to explore the reasons for differences. Many thanks to all participants in this survey: Reinhold Schmidt (Austria), Jean-Pierre Brion (Belgium), Jakub Hort, Ales Bartos (Czech Republic), Gunhild Waldemar (Denmark), Bruno Dubois (France), Alexander Tsiskaridze (Georgia), Hayrettin Tumani, Katharina Buerger (Germany), Elisabeth Kapaki (Greece), Peter Klivenyi (Hungary),Judith Aharon-Peretz (Israel), Giovanni Frisoni, Antonio Federico, Lucilla Parnetti, Daniella Galimberti, Alessandra Bizarro, (Italy), Gintaras Kaubrys (Lithuania), Frank-Erik de Leeuw (Netherland), Olaf Aaserud, Tormod Fladby (Norway), Konrad Rejdak (Poland), Alexandre Mendonca (Portugal), Bogdan Popescu (Romania), Elka Stefanova (Serbia) Pablo Martinez-Lage (Spain), Zuzana Gdovinova (Slovakia), Miro Denišlič (Slovenia), Carsten Wikkelso (Sweden), Hakan Gürvit (Turkey), Martin Rossor, Geoffrey Keir, Axel Petzold (United Kingdom) Note: The paper in full-text is already available at European Journal of Neurology 2009, doi:10.1111/j.1468-1331.2009.02753.x