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Impact of cerebro-spinal fluid biomarkers of Alzheimer’s disease in clinical practice: a multicentric study

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Abstract

CSF biomarkers of Alzheimer’s disease are well validated in clinical research; however, their pragmatic utility in daily practice is still unappreciated. These biomarkers are used in routine practice according to Health Authority Recommendations. In 604 consecutive patients explored for cognitive disorders, questionnaires were prospectively proposed and filled. Before and after CSF biomarker results, clinicians provided a diagnosis and an estimate of their diagnostic confidence. Analysis has compared the frequency of diagnosis before and after CSF biomarker results using the net reclassification improvement (NRI) method. We have evaluated external validity comparing with data of French Bank National of AD (BNA). A total of 561 patients [Alzheimer’s disease (AD), n = 253; non-AD, n = 308] were included (mean age, 68.6 years; women, 52 %). Clinically suspected diagnosis and CSF results were concordant in 65.2 % of cases. When clinical hypothesis and biological results were discordant, a reclassification occurred in favour of CSF biomarkers results in 76.9 %. The NRI was 39.5 %. In addition, the results show a statistically significant improvement in clinician confidence for their diagnosis. In comparison with BNA data, patients were younger and more frequently diagnosed with AD. Clinicians tend to heavily rely on the CSF AD biomarkers results and are more confident in their diagnoses using CSF AD biomarkers. Thus, these biomarkers appear as a key tool in clinical practice.

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Abbreviations

Aβ:

Amyloid β

AD:

Alzheimer disease

CT:

Computed tomography

CBD:

Corticobasal degeneration

CSF:

Cerebrospinal fluid

FTD:

Frontotemporal dementia

LBD:

Lewy body dementia

LP:

Lumbar puncture

MCI:

Mild cognitive impairment

MRI:

Magnetic resonance imaging

PET:

Positron emission tomography

P-tau:

Tau phosphorylated at threonine-181

SPECT:

Single photon emission computed tomography

T-tau:

Total tau

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Acknowledgments

We thank all the patients who were involved in this study and their physicians that accepted to fill in questionnaires that constitute the ISAC network: F. Blanc, MD; B. Crétin MD (University Hospital of Strasbourg, Co-Investigator); L. Volpegillot, MD (Saint-Joseph Hospital, Paris, Co-Investigator); L. Bernard-Bourzeix, MD (University Hospital of Limoges, Co-Investigator); M.N. Cuffi, MD (Castres Hospital; Co-Investigator); A.S. Carret-Rebillat, MD (Leopold Bellan Hospital and Inserm U942, Paris, Co-Investigator); L. Cohen, MD (University Hospital of Grenoble Hospital, Co-Investigator); A. Rollin, MD (University Hospital of Lille, Co-Investigator); F. Lebert MD (University Hospital of Lille, Co-Investigator); M. Sauvée, MD (University Hospital of Nancy, Co-Investigator); O. Vercruysse, MD (University Hospital of Lille, Co-Investigator); O. Hanon MD, PhD; ML. Seux, MD (Univerisity Hospital of Broca APHP, Co-Investigator); E. Dionet MD,(University Hospital of Clermont-Ferrand, Co-Investigator); A. Debart, MD (University Hospital of Reims, Co-Investigator), J. Delrieu, MD (University Hospital of Toulouse, Co-Investigator); O.Dereeper, MD (Calais Hospital, Co-Investigator), J. d’Avigneau (Cholet, Co-investigator). We also thank Joel Ménard, Patrick Trunet, Hervé Maisonneuve for critical revision of the manuscript and statistical advices. We thank Amel Rouis and Roland Chevrier for providing statistical data and analysis from BNA. We thank DIU plan Alzheimer for critical revision and advices.

Conflicts of interest

The study has no sponsor. F. Mouton-Liger, reports no disclosures. D. Wallon received travel expense from Novartis. A.C. Troussiere, Yatimi report no disclosures. J. Dumurgier received travel expense from Novartis. E. Magnin, V. de la Sayette, E. Duron, N. Philippi, E. Beaufils, A. Gabelle, B. Croisile, P. Robert, D. Hannequin report no disclosure. F. Pasquier has received consultancy honorarium from ESAI. Pr. Hugon has received consultancy honorarium from Novartis, Lundbeck. C. Paquet has received travel expense from Novartis.

Author information

Authors and Affiliations

  1. Centre Mémoire de Ressources et de Recherche (CMRR) Paris Nord Ile de France, Groupe hospitalier Lariboisière FW Saint Louis, APHP, Université Paris Diderot, 200, rue du Faubourg Saint Denis, 75010, Paris, France

    François Mouton-Liger, Julien Dumurgier, Jacques Hugon & Claire Paquet

  2. Inserm U942, Paris, France

    François Mouton-Liger & Claire Paquet

  3. Unité d’Histologie et de Biologie du Vieillissement, Groupe Hospitalier Lariboisiere FW Saint Louis, APHP, Université Paris Diderot, Paris, France

    François Mouton-Liger & Claire Paquet

  4. Centre Mémoire (CMRR) and INSERM UMR1079, Hôpital Universitaire de Rouen, 76000, Rouen, France

    David Wallon & Didier Hannequin

  5. Centre Mémoire (CMRR) de Lille, Université Lille Nord de France, UDSL, 59000, Lille, France

    Anne-Cécile Troussière & Florence Pasquier

  6. CMRR/EA COBTEK, CHU, Université de Nice Sophia Antipolis, Nice, France

    Rachida Yatimi & Philippe Robert

  7. Centre Mémoire (CMRR) de Besançon, Hôpital Universitaire de Besançon, 25000, Besançon, France

    Eloi Magnin

  8. Centre Mémoire (CMRR) de Caen, Hôpital Universitaire de Caen, 14000, Caen, France

    Vincent de la Sayette

  9. Centre Mémoire (CMRR) Paris Sud, Hôpital Broca, APHP, Université Paris V, 75000, Paris, France

    Emannuelle Duron

  10. Centre Mémoire (CMRR) de Strasbourg, Hôpital Universitaire Strasbourg, 67000, Strasbourg, France

    Nathalie Philippi

  11. Centre Mémoire (CMRR) de Tours, Hôpital Universitaire Tours, 37000, Tours, France

    Emilie Beaufils

  12. Centre Mémoire (CMRR) de Montpellier, Hôpital Universitaire Montpellier, 34000, Montpellier, France

    Audrey Gabelle

  13. Centre Mémoire (CMRR) de Lyon, Hôpital Universitaire Lyon, 69000, Lyon, France

    Bernard Croisile

Authors
  1. François Mouton-Liger
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  2. David Wallon
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  3. Anne-Cécile Troussière
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  4. Rachida Yatimi
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  5. Julien Dumurgier
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  6. Eloi Magnin
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  7. Vincent de la Sayette
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  8. Emannuelle Duron
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  9. Nathalie Philippi
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  10. Emilie Beaufils
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  11. Audrey Gabelle
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  12. Bernard Croisile
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  13. Philippe Robert
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  14. Florence Pasquier
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  15. Didier Hannequin
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  16. Jacques Hugon
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  17. Claire Paquet
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Corresponding author

Correspondence to Claire Paquet.

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For the ISAC network.

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Mouton-Liger, F., Wallon, D., Troussière, AC. et al. Impact of cerebro-spinal fluid biomarkers of Alzheimer’s disease in clinical practice: a multicentric study. J Neurol 261, 144–151 (2014). https://doi.org/10.1007/s00415-013-7160-3

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  • DOI: https://doi.org/10.1007/s00415-013-7160-3

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