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01.01.2014 | Original Communication

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

verfasst von: 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

Erschienen in: Journal of Neurology | Ausgabe 1/2014

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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.

Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, Snyder PJ, Carrillo MC, Thies B, Phelps CH (2011) The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7:270–279PubMedCentralCrossRefPubMed

Andreasson U, Lautner R, Schott JM, Mattsson N, Hansson O, Herukka SK, Helisalmi S, Ewers M, Hampel H, Wallin A, Minthon L, Hardy J, Blennow K, Zetterberg H (2013) CSF biomarkers for Alzheimer’s pathology and the effect size of APOE epsilon4. Mol Psychiatry. doi:10.1038/mp.2013.18 PubMedCentralPubMed

Beach TG, Monsell SE, Phillips LE, Kukull W (2012) Accuracy of the clinical diagnosis of Alzheimer disease at National Institute on Aging Alzheimer Disease Centers, 2005–2010. J Neuropathol Exp Neurol 71:266–273PubMedCentralCrossRefPubMed

Bian H, Van Swieten JC, Leight S, Massimo L, Wood E, Forman M, Moore P, de Koning I, Clark CM, Rosso S, Trojanowski J, Lee VM, Grossman M (2008) CSF biomarkers in frontotemporal lobar degeneration with known pathology. Neurology 70:1827–1835PubMedCentralCrossRefPubMed

Blennow K, Hampel H, Weiner M, Zetterberg H (2010) Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol 6:131–144CrossRefPubMed

Brunnstrom H, Rawshani N, Zetterberg H, Blennow K, Minthon L, Passant U, Englund E (2010) Cerebrospinal fluid biomarker results in relation to neuropathological dementia diagnoses. Alzheimers Dement 6:104–109CrossRefPubMed

De Lepeleire J, Wind AW, Iliffe S, Moniz-Cook ED, Wilcock J, Gonzalez VM, Derksen E, Gianelli MV, Vernooij-Dassen M, Interdem G (2008) The primary care diagnosis of dementia in Europe: an analysis using multidisciplinary, multinational expert groups. Aging Ment Health 12:568–576CrossRefPubMed

Derksen E, Vernooij-Dassen M, Gillissen F, Olde Rikkert M, Scheltens P (2006) Impact of diagnostic disclosure in dementia on patients and carers: qualitative case series analysis. Aging Ment Health 10:525–531CrossRefPubMed

Dumurgier J, Gabelle A, Vercruysse O, Bombois S, Laplanche JL, Peoc’h K, Schraen S, Sablonniere B, Pasquier F, Touchon J, Lehmann S, Hugon J, Paquet C (2013) Exacerbated CSF abnormalities in younger patients with Alzheimer’s disease. Neurobiol Dis 54:486–491CrossRefPubMed

10.

Dumurgier J, Vercruysse O, Paquet C, Bombois S, Chaulet C, Laplanche JL, Peoc’h K, Schraen S, Pasquier F, Touchon J, Hugon J, Lehmann S, Gabelle A (2012) Intersite variability of CSF Alzheimer’s disease biomarkers in clinical setting. Alzheimers Dement 9(4):406–413CrossRefPubMed

11.

Gabelle A, Dumurgier J, Vercruysse O, Paquet C, Bombois S, Laplanche JL, Peoc’h K, Schraen S, Buee L, Pasquier F, Hugon J, Touchon J, Lehmann S (2013) Impact of the 2008–2012 French Alzheimer plan on the use of cerebrospinal fluid biomarkers in research memory center: the PLM study. J Alzheimers Dis 34:297–305PubMed

12.

Grundman M, Pontecorvo MJ, Salloway SP, Doraiswamy PM, Fleisher AS, Sadowsky CH, Nair AK, Siderowf A, Lu M, Arora AK, Agbulos A, Flitter ML, Krautkramer MJ, Skovronsky DM, Mintun MA, Group AS (2013) Potential impact of amyloid imaging on diagnosis and intended management in patients with progressive cognitive decline. Alzheimer Dis Assoc Disord 27:4–15CrossRefPubMed

13.

Kester MI, Boelaarts L, Bouwman FH, Vogels RL, Groot ER, van Elk EJ, Blankenstein MA, van der Flier WM, Scheltens P (2010) Diagnostic impact of CSF biomarkers in a local hospital memory clinic. Dement Geriatr Cogn Disord 29:491–497CrossRefPubMed

14.

Knopman DS, DeKosky ST, Cummings JL, Chui H, Corey-Bloom J, Relkin N, Small GW, Miller B, Stevens JC (2001) Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 56:1143–1153CrossRefPubMed

15.

Le Duff F, Develay AE, Quetel J, Lafay P, Schuck S, Pradier C, Robert P, French National Alzheimer d (2012) The 2008–2012 French Alzheimer plan: description of the national Alzheimer information system. J Alzheimers Dis 29:891–902PubMed

16.

Lim A, Tsuang D, Kukull W, Nochlin D, Leverenz J, McCormick W, Bowen J, Teri L, Thompson J, Peskind ER, Raskind M, Larson EB (1999) Clinico-neuropathological correlation of Alzheimer’s disease in a community-based case series. J Am Geriatr Soc 47:564–569CrossRefPubMed

17.

Mattsson N, Andreasson U, Persson S, Arai H, Batish SD, Bernardini S, Bocchio-Chiavetto L, Blankenstein MA, Carrillo MC, Chalbot S, Coart E, Chiasserini D, Cutler N, Dahlfors G, Duller S, Fagan AM, Forlenza O, Frisoni GB, Galasko D, Galimberti D, Hampel H, Handberg A, Heneka MT, Herskovits AZ, Herukka SK, Holtzman DM, Humpel C, Hyman BT, Iqbal K, Jucker M, Kaeser SA, Kaiser E, Kapaki E, Kidd D, Klivenyi P, Knudsen CS, Kummer MP, Lui J, Llado A, Lewczuk P, Li QX, Martins R, Masters C, McAuliffe J, Mercken M, Moghekar A, Molinuevo JL, Montine TJ, Nowatzke W, O’Brien R, Otto M, Paraskevas GP, Parnetti L, Petersen RC, Prvulovic D, de Reus HP, Rissman RA, Scarpini E, Stefani A, Soininen H, Schroder J, Shaw LM, Skinningsrud A, Skrogstad B, Spreer A, Talib L, Teunissen C, Trojanowski JQ, Tumani H, Umek RM, Van Broeck B, Vanderstichele H, Vecsei L, Verbeek MM, Windisch M, Zhang J, Zetterberg H, Blennow K (2011) The Alzheimer’s association external quality control program for cerebrospinal fluid biomarkers. Alzheimers Dement 7(386–395):e386CrossRef

18.

Mattsson N, Zetterberg H, Blennow K (2010) Lessons from multicenter studies on CSF biomarkers for Alzheimer’s disease. Int J Alzheimers Dis. doi:10.4061/2010/610613

19.

McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA work group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s disease. Neurology 34:939–944CrossRefPubMed

20.

McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH (2011) The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7:263–269PubMedCentralCrossRefPubMed

21.

Moons KG, de Groot JA, Linnet K, Reitsma JB, Bossuyt PM (2012) Quantifying the added value of a diagnostic test or marker. Clin Chem 58:1408–1417CrossRefPubMed

22.

Paquet C, Latour F, Saulnier I, Hanon O (2012) Multicenter study on lumbar puncture indication, clinical practice and feasibility. Rev Neurol (Paris) 168:28–32CrossRef

23.

Petersen RC, Aisen PS, Beckett LA, Donohue MC, Gamst AC, Harvey DJ, Jack CR Jr, Jagust WJ, Shaw LM, Toga AW, Trojanowski JQ, Weiner MW (2010) Alzheimer’s disease neuroimaging initiative (ADNI): clinical characterization. Neurology 74:201–209PubMedCentralCrossRefPubMed

24.

Ranginwala NA, Hynan LS, Weiner MF, White CL 3rd (2008) Clinical criteria for the diagnosis of Alzheimer disease: still good after all these years. Am J Geriatr Psychiatry 16:384–388CrossRefPubMed

25.

Rinne JO, Brooks DJ, Rossor MN, Fox NC, Bullock R, Klunk WE, Mathis CA, Blennow K, Barakos J, Okello AA, Martinez Rodriguez, de Liano S, Liu E, Koller M, Gregg KM, Schenk D, Black R, Grundman M (2010) 11C-PiB PET assessment of change in fibrillar amyloid-beta load in patients with Alzheimer’s disease treated with bapineuzumab: a phase 2, double-blind, placebo-controlled, ascending-dose study. Lancet Neurol 9:363–372CrossRefPubMed

26.

Santos AN, Ewers M, Minthon L, Simm A, Silber RE, Blennow K, Prvulovic D, Hansson O, Hampel H (2012) Amyloid-beta oligomers in cerebrospinal fluid are associated with cognitive decline in patients with Alzheimer’s disease. J Alzheimers Dis 29:171–176PubMed

27.

Schoonenboom NS, Reesink FE, Verwey NA, Kester MI, Teunissen CE, van de Ven PM, Pijnenburg YA, Blankenstein MA, Rozemuller AJ, Scheltens P, van der Flier WM (2012) Cerebrospinal fluid markers for differential dementia diagnosis in a large memory clinic cohort. Neurology 78:47–54CrossRefPubMed

28.

Smits LL, Pijnenburg YA, Koedam EL, van der Vlies AE, Reuling IE, Koene T, Teunissen CE, Scheltens P, van der Flier WM (2012) Early onset Alzheimer’s disease is associated with a distinct neuropsychological profile. J Alzheimers Dis 30:101–108PubMed

29.

Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, Iwatsubo T, Jack CR Jr, Kaye J, Montine TJ, Park DC, Reiman EM, Rowe CC, Siemers E, Stern Y, Yaffe K, Carrillo MC, Thies B, Morrison-Bogorad M, Wagster MV, Phelps CH (2011) Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7:280–292PubMedCentralCrossRefPubMed

30.

Strozyk D, Blennow K, White LR, Launer LJ (2003) CSF Abeta 42 levels correlate with amyloid-neuropathology in a population-based autopsy study. Neurology 60:652–656CrossRefPubMed

31.

Tapiola T, Alafuzoff I, Herukka SK, Parkkinen L, Hartikainen P, Soininen H, Pirttila T (2009) Cerebrospinal fluid (beta)-amyloid 42 and tau proteins as biomarkers of Alzheimer-type pathologic changes in the brain. Arch Neurol 66:382–389CrossRefPubMed

32.

Vanderstichele HM, Shaw L, Vandijck M, Jeromin A, Zetterberg H, Blennow K, Teunissen C, Engelborghs S (2013) Alzheimer disease biomarker testing in cerebrospinal fluid: a method to harmonize assay platforms in the absence of an absolute reference standard. Clin Chem 59(4):710–712CrossRefPubMed

33.

Warren JD, Fletcher PD, Golden HL (2012) The paradox of syndromic diversity in Alzheimer disease. Nat Rev Neurol 8:451–464PubMed

Titel: Impact of cerebro-spinal fluid biomarkers of Alzheimer’s disease in clinical practice: a multicentric study
verfasst von: 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
Publikationsdatum: 01.01.2014
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Neurology / Ausgabe 1/2014
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-013-7160-3

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