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Folia Neuropathologica
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vol. 56
Original paper

The Erlangen Score Algorithm in the diagnosis and prediction of the progression from subjective cognitive decline and mild cognitive impairment to Alzheimer-type dementia

Anna Filipek-Gliszczyńska, Anna Barczak, Magdalena Budziszewska, Monika Mandecka, Tomasz Gabryelewicz, Maria Barcikowska

Folia Neuropathol 2018; 56 (2): 88-96
Online publish date: 2018/06/28
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The evaluation of cerebrospinal fluid (CSF) biomarkers for Alzheimer’s disease (AD) (β-amyloid, t-tau, p-tau) can be used to estimate the risk of developing dementia in patients at the pre-clinical stages of AD, i.e. subjective cognitive decline (SCD) and mild cognitive impairment (MCI). Erlangen Score Algorithm allows interpretation of CSF biomarker concentrations and is cut-off value independent. The aim of this study was to establish if this algorithm can be applied for routine diagnostic testing in clinical and preclinical subjects and has prognostic value. We analysed 217 patients from the memory clinic with the diagnosis of SCD (n = 31), MCI (n = 104), and AD (n = 82) with clinical follow-up amounting to 14.33 months (SD = 6.82). It was found that the highest Erlangen Score dominated in the AD group and was the rarest in the SCD group. In the group of patients with progression of symptoms during our period of observation, the AD pathology was confirmed in 93.75% of cases. Among the non-progressing subjects (n = 119) the algorithm indicated the risk of developing AD as possible in 40.34% and probable in 15.97% of cases. To conclude, the Erlangen Score Algorithm is a useful tool to determinate the risk of developing AD before the onset of dementia or to confirm the AD diagnosis. It is extremely valuable in preclinical stages of AD for planning purposes and early intervention as well as for future clinical trials.

Alzheimer’s disease, mild cognitive impairment, subjective cognitive decline, cerebrospinal fluid biomarkers, Erlangen Score Algorithm

Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WI, Petersen RC, Snyder PJ, Carillo MC, Thies B, Phelps CH. 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 2011; 7: 270-279.
Avila JP, Lucas J. Role of tau protein in both physiological and pathological conditions. Physiol Rev 2004; 84: 361-384.
Blennow K. Cerebrospinal fluid protein biomarkers for Alzheimer’s disease. NeuroRx 2004; 1: 213-225.
Blennow K, Vanmechelen E. CSF markers for pathogenic processes in Alzheimer’s disease: diagnostic implications and use in clinical neurochemistry. Brain Res Bull 2003; 61: 235-342.
Clark CM, Xie S, Chittams J, Ewbank D, Peskind E, Galasko D, Morris JC, McKeel DW Jr, Farlow M, Weitlauf SL, Quinn J, Kaye J, Knopman D, Arai H, Doody RS, DeCarli C, Leight S, Lee VM, Trojanowski JQ. Cerebrospinal fluid tau and beta-amyloid: how well do these bio-markers reflect autopsy-confirmed dementia diagnoses? Arch Neurol 2003; 60: 1696-1702.
Fagan AM, Roe CM, Xiong C, Mintun MA, Morris JC, Holtzman DM. Cerebrospinal fluid tau/beta-amyloid(42) ratio as a prediction of cognitive decline in nondemented older adults. Arch Neurol 2007; 64: 343-349.
Fagan AM, Shaw LM, Xiong C, Vanderstichele H, Mintun MA, Trojanowski JQ, Coart E, Moriss JC, Holtzman DM. Comparison of analytical platforms for cerebrospinal fluid measures of beta-amyloid 1-42, total tau, and p-tau181 for identifying Alzheimer disease amyloid plaque pathology. Arch Neurol 2011; 68: 1137-1144.
Formichi P, Battisti C, Radi E, Federico A. Cerebrospinal fluid tau, A beta, and phosphorylated tau protein for the diagnosis of Alzheimer’s disease. J Cell Physiol 2006; 208: 39-46.
Frölich L, Peters O, Lewczuk P, Gruber O, Teipel SJ, Gertz HJ, Jahn H, Jessen F, Kurz A, Luckhaus C, Hüll M, Pantel J, Reischies FM, Schröder J, Wagner M, Rienhoff O, Wolf S, Bauer C, Schuchhardt J, Heuser I, Rüther E, Henn F, Maier W, Wiltfang J, Kornhuber J. Incremental value of biomarker combinations to predict progression of mild cognitive impairment to Alzheimer’s dementia. Alzheimers Res Ther 2017; 9: 84.
Hesse C, Rosengren L, Andreasen N, Davidsson P, Vanderstichele H, Vanmechelen E, Blennow K. Transient increase in total tau but not phospho-tau in human cerebrospinal fluid after acute stroke. Neurosci Lett 2001; 297: 187-190.
Itoh N, Arai H, Urakami K, Ishiguro K, Ohno H, Hampel H, Buerger K, Wiltfang J, Otto M, Kretzschmar H, Moeller HJ, Imagawa M, Kohno H, Nakashima K, Kuzuhara S, Sasaki H, Imahori K. Large-scale, multicenter study of cerebrospinal fluid tau protein phosphorylated at serine 199 for the antemortem diagnosis of Alzheimer’s disease. Ann Neurol 2001; 50: 150-156.
Jessen F, Amariglio RE, van Boxtel M, Breteler M, Ceccaldi M, Chételat G, et al.; Subjective Cognitive Decline Initiative (SCD-I) Working Group. A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer’s disease. Alzheimers Dement 2014; 10: 844-852.
Lewczuk P, Kornhuber J, Toledo JB, Trojanowski JQ, Knapik Czajka M, Peters O, Wiltfang J, Shaw LM; US-ADNI. Validation of the Erlangen Score Algorithm for the prediction of the development of dementia due to Alzheimer’s disease in pre-dementia subjects. J Alzheimers Dis 2015; 48: 433-441.
Lewczuk P, Kornhuber J, Wiltfang J. The German Competence Net Dementias: standard operating procedures for the neurochemical dementia diagnostics. J Neural Transm (Vienna) 2006; 113: 1075-1080.
Lewczuk P, Zimmermann R, Wiltfang J, Kornhuber J. Neurochemical dementia diagnostics: a simple algorithm for interpretation of the CSF biomarkers. J Neural Transm (Vienna) 2009; 116: 1163-1167.
Maddalena A, Papassotiropoulos A, Muller-Tillmanns B, Jung HH, Hegi T, Nitsch RM, Hock C. Biochemical diagnosis of Alzheimer disease by measuring the cerebrospinal fluid ratio of phosphorylated tau protein to beta-amyloid peptide42. Arch Neurol 2003; 60: 1202-1206.
Mandecka M, Budziszewska M, Barczak A, Pepłonska B, Chodakowska-Zebrowska M, Filipek-Gliszczynska A, Nesteruk M, Styczynska M, Barcikowska M, Gabryelewicz T. Association between cerebrospinal fluid biomarkers for Alzheimer’s disease, APOE genotypes and auditory verbal learning task in subjective cognitive decline, mild cognitive impairment and Alzheimer’s disease. J Alzheimers Dis 2016; 54: 157-168.
Mattsson N, Insel P, Nosheny R, Zetterberg H, Trojanowski JQ, Shaw LM, Tosun D, Weiner M; Alzheimer’s Disease Neuroimaging Initiative. CSF protein biomarkers predicting longitudinal reduction of CSF beta-amyloid42 in cognitively healthy elders. Transl Psychiatry 2013; 3: e293.
Mattsson N, Zetterberg H, Hansson O, Andreasen N, Parnetti L, Jonsson M, Herukka SK, van der Flier WM, Blankenstein MA, Ewers M, Rich K, Kaiser E, Verbeek M, Tsolaki M, Mulugeta E, Rosen E, Aarsland D, Visser JP, Schroder J, Marcusson J, de Lon M, Hampel H, Scheltens P, Pritilla T, Walin A, Jonhagen ME, Minthon L, Winblad B, Blennow K. CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. Am Med Assoc 2009; 302: 385-293.
Molinuevo JL, Blennow K, Dubois B, Engelborghs S, Lewczuk P, Perret-Liaudet A, Teunissen CE, Parnetti L. The clinical use of cerebrospinal fluid biomarker testing for Alzheimer’s disease diagnosis: A consensus paper from the Alzheimer’s biomarkers standardization initiative. Alzheimers Dement 2014; 10: 808-817.
Molinuevo JL, Gispert JD, Dubois B, Heneka MT, Lleo A, Engelborghs S, Pujol J, de Souza LC, Alcolea D, Jessen F. The AD-CSF-Index discriminates Alzheimer’s disease patients from healthy controls: A validation study. J Alzheimers Dis 2013; 36: 67-77.
Morris JC. Early-stage and preclinical Alzheimer disease. Alzheimer Dis Assoc Disord 2005; 19: 163-165.
Nagga K, Gottfries J, Blennow K, Marcusson J. Cerebrospinal fluid phospho-tau, total tau and beta-amyloid (1-42) in the differentiation between Alzheimer’s disease and vascular dementia. Dement Geriatr Cogn Disord 2002; 14: 183-190.
Nesteruk M, Nesteruk T, Styczyńska M, Barczak A, Mandecka M, Walecki J, Barcikowska-Kotowicz M. Predicting the conversion of mild cognitive impairment to Alzheimer’s disease based on the volumetric measurements of the selected brain structures in magnetic resonance imaging. Neurol Neurochir Pol 2015; 49: 349-353.
Nesteruk M, Nesteruk T, Styczyńska M, Mandecka M, Barczak A, Barcikowska M. Combined use of biochemical and volumetric biomarkers to assess the risk of conversion of mild cognitive impairment to Alzheimer’s disease. Folia Neuropathol 2016; 54: 369-374.
Parnetti L, Chiasserini D, Eusebi P, Giannandrea D, Bellomo G, De Carlo C, Padiglioni C, Mastrocola S, Lisetti V, Calabresi P. Performance of abeta1-40, abeta1-42, total tau, and phosphorylated tau as predictors of dementia in a cohort of patients with mild cognitive impairment. J Alzheimers Dis 2012; 29: 229-238.
Parnetti L, Lanari A, Amici S, Gallai V, Vanmechelen E, Hulstaert F. CSF phosphorylated tau is possible marker for discriminating Alzheimer’s disease from dementia with Lewi bodies. Neurol Sci 2001: 22: 77-78.
Prestia A, Caroli A, Herholz K, Reiman E, Chen K, Jagust WJ, Frisoni GB. Translational Outpatient Memory Clinic Working Group; Alzheimer’s Disease Neuroimaging Initiative. Diagnostic accuracy of markers for prodromal Alzheimer’s disease in independent clinical series. Alzheimers Dement 2013; 9: 677-686.
Peteresen RC. Mild cognitive impairment as diagnostic entity. J Intern Med 2004; 256: 183-194.
Shaw LM, Vanderstichele H, Knapik-Czajka M, Clark CM, Aisen PS, Petersen RC, Blennow K, Soares H, Simon A, Lewczuk P, Dean R, Siemers E, Potter W, Lee VM, Trojanowski JQ. Cerebrospinal fluid biomarker signature in Alzheimer’s disease neuroimaging initiative subjects. Ann Neurol 2009; 65: 403-413.
Sjögren M, Davidsson P, Tulberg M, Minthon L, Wallin A, Wikkelso C, Granérus AK, Vanderstichele H, Vanmechelen E, Blennow K. Both total and phosphorylated tau are increased in Alzheimer’s disease. J Neurol Neurosurg Psychiatr 2001; 70: 624-630.
Sjögren M, Davidsson P, Wallin A, Granérus AK, Grundström E, Askmark H, Vanmechelen E, Blennow K. Decreased CSF-beta-amyloid 42 in Alzheimer’s disease and amyotrophic lateral sclerosis may reflect mismetabolism of beta-amyloid induced by disparate mechanisms. Demen Geriatr Cogn Disord 2002; 13: 1112-1118.
Vanmechelen E, Vanderstichele H, Davidsson P, Van Kerschaver E, Van der Perre B, Sjogren M, Andreasen N, Blennow K. Quantification of tau phosphorylated at threonine 181 in human cerebrospinal fluid: a sandwich ELISA with a synthetic phosphopeptide for standardization. Neurosci Lett 2000; 285: 49-52.
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