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Journal of Neurology

, Volume 261, Issue 1, pp 144–151 | Cite as

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

  • François Mouton-Liger
  • David Wallon
  • Anne-Cécile Troussière
  • Rachida Yatimi
  • Julien Dumurgier
  • Eloi Magnin
  • Vincent de la Sayette
  • Emannuelle Duron
  • Nathalie Philippi
  • Emilie Beaufils
  • Audrey Gabelle
  • Bernard Croisile
  • Philippe Robert
  • Florence Pasquier
  • Didier Hannequin
  • Jacques Hugon
  • Claire Paquet
Original Communication

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.

Keywords

Cerebrospinal fluid Biomarkers Alzheimer’s disease Clinical practice 

Abbreviations

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

Notes

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.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • François Mouton-Liger
    • 1
    • 2
    • 3
  • David Wallon
    • 4
  • Anne-Cécile Troussière
    • 5
  • Rachida Yatimi
    • 6
  • Julien Dumurgier
    • 1
  • Eloi Magnin
    • 7
  • Vincent de la Sayette
    • 8
  • Emannuelle Duron
    • 9
  • Nathalie Philippi
    • 10
  • Emilie Beaufils
    • 11
  • Audrey Gabelle
    • 12
  • Bernard Croisile
    • 13
  • Philippe Robert
    • 6
  • Florence Pasquier
    • 5
  • Didier Hannequin
    • 4
  • Jacques Hugon
    • 1
  • Claire Paquet
    • 1
    • 2
    • 3
  1. 1.Centre Mémoire de Ressources et de Recherche (CMRR) Paris Nord Ile de FranceGroupe hospitalier Lariboisière FW Saint Louis, APHP, Université Paris DiderotParisFrance
  2. 2.Inserm U942ParisFrance
  3. 3.Unité d’Histologie et de Biologie du VieillissementGroupe Hospitalier Lariboisiere FW Saint Louis, APHP, Université Paris DiderotParisFrance
  4. 4.Centre Mémoire (CMRR) and INSERM UMR1079Hôpital Universitaire de RouenRouenFrance
  5. 5.Centre Mémoire (CMRR) de LilleUniversité Lille Nord de France, UDSLLilleFrance
  6. 6.CMRR/EA COBTEK, CHUUniversité de Nice Sophia AntipolisNiceFrance
  7. 7.Centre Mémoire (CMRR) de BesançonHôpital Universitaire de BesançonBesançonFrance
  8. 8.Centre Mémoire (CMRR) de CaenHôpital Universitaire de CaenCaenFrance
  9. 9.Centre Mémoire (CMRR) Paris SudHôpital Broca, APHP, Université Paris VParisFrance
  10. 10.Centre Mémoire (CMRR) de StrasbourgHôpital Universitaire StrasbourgStrasbourgFrance
  11. 11.Centre Mémoire (CMRR) de ToursHôpital Universitaire ToursToursFrance
  12. 12.Centre Mémoire (CMRR) de MontpellierHôpital Universitaire MontpellierMontpellierFrance
  13. 13.Centre Mémoire (CMRR) de LyonHôpital Universitaire LyonLyonFrance

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