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Published in: Alzheimer's Research & Therapy 1/2018

Open Access 01-12-2018 | Research

Addition of the Aβ42/40 ratio to the cerebrospinal fluid biomarker profile increases the predictive value for underlying Alzheimer’s disease dementia in mild cognitive impairment

Authors: Inês Baldeiras, Isabel Santana, Maria João Leitão, Helena Gens, Rui Pascoal, Miguel Tábuas-Pereira, José Beato-Coelho, Diana Duro, Maria Rosário Almeida, Catarina Resende Oliveira

Published in: Alzheimer's Research & Therapy | Issue 1/2018

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Abstract

Background

Cerebrospinal fluid (CSF) biomarkers have been used to increase the evidence of underlying Alzheimer’s disease (AD) pathology in mild cognitive impairment (MCI). However, CSF biomarker-based classification often results in conflicting profiles with controversial prognostic value. Normalization of the CSF Aβ42 concentration to the level of total amyloid beta (Aβ), using the Aβ42/40 ratio, has been shown to improve the distinction between AD and non-AD dementia. Therefore, we evaluated whether the Aβ42/40 ratio would improve MCI categorization and more accurately predict progression to AD.

Methods

Our baseline population consisted of 197 MCI patients, of which 144 had a follow-up ≥ 2 years, and comprised the longitudinal study group. To establish our own CSF Aβ42/40 ratio reference value, a group of 168 AD-dementia patients and 66 neurological controls was also included. CSF biomarker-based classification was operationalized according to the framework of the National Institute of Aging–Alzheimer Association criteria for MCI.

Results

When using the core CSF biomarkers (Aβ42, total Tau and phosphorylated Tau), 30% of the patients fell into the high-AD-likelihood (HL) group (both amyloid and neurodegeneration markers positive), 30% into the low-AD-likelihood group (all biomarkers negative), 28% into the suspected non-Alzheimer pathophysiology (SNAP) group (only neurodegeneration markers positive) and 12% into the isolated amyloid pathology group (only amyloid-positive). Replacing Aβ42 by the Aβ42/40 ratio resulted in a significant increase in the percentage of patients with amyloidosis (42–59%) and in the proportion of interpretable biological profiles (61–75%), due to a reduction by half in the number of SNAP cases and an increase in the proportion of the HL subgroup. Survival analysis showed that risk of progression to AD was highest in the HL group, and increased when the Aβ42/40 ratio, instead of Aβ42, combined with total Tau and phosphorylated Tau was used for biomarker-based categorization.

Conclusions

Our results confirm the usefulness of the CSF Aβ42/40 ratio in the interpretation of CSF biomarker profiles in MCI patients, by increasing the proportion of conclusive profiles and enhancing their predictive value for underlying AD.
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Literature
1.
go back to reference Prince M, Wimo A, Guerchet M, Ali G, Wu Y, Prina M. World Alzheimer Report 2015. The global impact of dementia. An analysis of prevalence, incidence, cost & trends. London: Alzheimer’s Disease International (ADI); 2015. Prince M, Wimo A, Guerchet M, Ali G, Wu Y, Prina M. World Alzheimer Report 2015. The global impact of dementia. An analysis of prevalence, incidence, cost & trends. London: Alzheimer’s Disease International (ADI); 2015.
2.
go back to reference Morris JC. Early-stage and preclinical Alzheimer disease. Alzheimer Dis Assoc Disord. 2005;1:163–76. Morris JC. Early-stage and preclinical Alzheimer disease. Alzheimer Dis Assoc Disord. 2005;1:163–76.
3.
go back to reference Jansen WJ, Ossenkoppele R, Knol DL, Tijms BM, Scheltens P, FRJ V, Visser PJ, Amyloid Biomarker Study Group. Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis. JAMA. 2015;313:1924–38.CrossRefPubMedPubMedCentral Jansen WJ, Ossenkoppele R, Knol DL, Tijms BM, Scheltens P, FRJ V, Visser PJ, Amyloid Biomarker Study Group. Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis. JAMA. 2015;313:1924–38.CrossRefPubMedPubMedCentral
4.
go back to reference Jack CR Jr, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, et al. Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurol. 2010;9:119–28.CrossRefPubMedPubMedCentral Jack CR Jr, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, et al. Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurol. 2010;9:119–28.CrossRefPubMedPubMedCentral
5.
go back to reference 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. 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. 2011;7:263–9.CrossRefPubMedPubMedCentral 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. 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. 2011;7:263–9.CrossRefPubMedPubMedCentral
6.
go back to reference Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzmn DM, Jaqust WJ, Petersen RC, Synder PJ, Carrillo 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;7:270–9.CrossRefPubMedPubMedCentral Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzmn DM, Jaqust WJ, Petersen RC, Synder PJ, Carrillo 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;7:270–9.CrossRefPubMedPubMedCentral
7.
go back to reference 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. 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. 2011;7:280–92.CrossRefPubMedPubMedCentral 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. 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. 2011;7:280–92.CrossRefPubMedPubMedCentral
8.
go back to reference Blennow K, Hampel H, Weiner M, Zetterberg H. Cerebrospinal fluid and blood biomarkers in Alzheimer’s diseases. Nat Rev Neurol. 2010;6:131–44.CrossRefPubMed Blennow K, Hampel H, Weiner M, Zetterberg H. Cerebrospinal fluid and blood biomarkers in Alzheimer’s diseases. Nat Rev Neurol. 2010;6:131–44.CrossRefPubMed
9.
go back to reference Olsson B, Lautner R, Andreasson U, Öhrfelt A, Portelius E, Bjerke M, Hölttä M, Rosén C, Olsson C, Strobel G, Wu E, Dakin K, Petzold M, Blennow K, Zetterberg H. CSF and blood biomarkers for the diagnosis of Alzheimer’s disease: a systematic review and meta-analysis. Lancet Neurol. 2016;15:673–84.CrossRefPubMed Olsson B, Lautner R, Andreasson U, Öhrfelt A, Portelius E, Bjerke M, Hölttä M, Rosén C, Olsson C, Strobel G, Wu E, Dakin K, Petzold M, Blennow K, Zetterberg H. CSF and blood biomarkers for the diagnosis of Alzheimer’s disease: a systematic review and meta-analysis. Lancet Neurol. 2016;15:673–84.CrossRefPubMed
10.
go back to reference Hansson O, Zetterberg H, Buchhave P, Londos E, Blennow K, Minthon L. Association between CSF biomarkers and incipient Alzheimer’s disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol. 2006;5:228–34.CrossRefPubMed Hansson O, Zetterberg H, Buchhave P, Londos E, Blennow K, Minthon L. Association between CSF biomarkers and incipient Alzheimer’s disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol. 2006;5:228–34.CrossRefPubMed
11.
go back to reference Hertze J, Minthon L, Zetterberg H, Vanmechelen E, Blennow K, Hansson O. Evaluation of CSF biomarkers as predictors of Alzheimer’s disease: a clinical follow-up study of 4.7 years. J Alzheimers Dis. 2010;21:1119–28.CrossRefPubMed Hertze J, Minthon L, Zetterberg H, Vanmechelen E, Blennow K, Hansson O. Evaluation of CSF biomarkers as predictors of Alzheimer’s disease: a clinical follow-up study of 4.7 years. J Alzheimers Dis. 2010;21:1119–28.CrossRefPubMed
12.
go back to reference Shaw L, 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. Alzheimer's Disease Neuroimaging Initiative. Cerebrospinal fluid biomarker signature in Alzheimer’s disease neuroimaging initiative subjects. Ann Neurol. 2009;65:403–13.CrossRefPubMedPubMedCentral Shaw L, 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. Alzheimer's Disease Neuroimaging Initiative. Cerebrospinal fluid biomarker signature in Alzheimer’s disease neuroimaging initiative subjects. Ann Neurol. 2009;65:403–13.CrossRefPubMedPubMedCentral
13.
go back to reference 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, Rosén E, Aarsland D, Visser PJ, Schröder J, Marcusson J, de Leon M, Hampel H, Scheltens P, Pirttilä T, Wallin A, Jönhagen ME, Minthon L, Winblad B, Blennow K. CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA. 2009;302:385–93.CrossRefPubMed 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, Rosén E, Aarsland D, Visser PJ, Schröder J, Marcusson J, de Leon M, Hampel H, Scheltens P, Pirttilä T, Wallin A, Jönhagen ME, Minthon L, Winblad B, Blennow K. CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA. 2009;302:385–93.CrossRefPubMed
14.
go back to reference Visser PJ, Verhey F, Knol DL, Scheltens P, Wahlund LO, Freund-Levi Y, Tsolaki M, Minthon L, Wallin AK, Hampel H, Bürger K, Pirttila T, Soininen H, Rikkert MO, Verbeek MM, Spiru L, Blennow K. Prevalence and prognostic value of CSF markers of Alzheimer's disease pathology in patients with subjective cognitive impairment or mild cognitive impairment in the DESCRIPA study: a prospective cohort study. Lancet Neurol. 2009;8:619–27.CrossRefPubMed Visser PJ, Verhey F, Knol DL, Scheltens P, Wahlund LO, Freund-Levi Y, Tsolaki M, Minthon L, Wallin AK, Hampel H, Bürger K, Pirttila T, Soininen H, Rikkert MO, Verbeek MM, Spiru L, Blennow K. Prevalence and prognostic value of CSF markers of Alzheimer's disease pathology in patients with subjective cognitive impairment or mild cognitive impairment in the DESCRIPA study: a prospective cohort study. Lancet Neurol. 2009;8:619–27.CrossRefPubMed
15.
go back to reference Blennow K, Dubois B, Fagan AM, Lewczuk P, de Leon MJ, Hampel H. Clinical utility of cerebrospinal fluid biomarkers in the diagnosis of early Alzheimer’s disease. Alzheimers Dement. 2015;11:58–69.CrossRefPubMed Blennow K, Dubois B, Fagan AM, Lewczuk P, de Leon MJ, Hampel H. Clinical utility of cerebrospinal fluid biomarkers in the diagnosis of early Alzheimer’s disease. Alzheimers Dement. 2015;11:58–69.CrossRefPubMed
16.
go back to reference Leitão MJ, Baldeiras I, Herukka SK, Pikkarainen M, Leinonen V, Simonsen AH, Perret-Liaudet A, Fourier A, Quadrio I, Veiga PM, de Oliveira CR. Chasing the effects of pre-analytical confounders—a multicenter study on CSF-AD biomarkers. Front Neurol. 2015;6:153.CrossRefPubMedPubMedCentral Leitão MJ, Baldeiras I, Herukka SK, Pikkarainen M, Leinonen V, Simonsen AH, Perret-Liaudet A, Fourier A, Quadrio I, Veiga PM, de Oliveira CR. Chasing the effects of pre-analytical confounders—a multicenter study on CSF-AD biomarkers. Front Neurol. 2015;6:153.CrossRefPubMedPubMedCentral
17.
go back to reference Lelental N, Brandner S, Kofanova O, Blennow K, Zetterberg H, Andreasson U, Engelborghs S, Mroczko B, Gabryelewicz T, Teunissen C, Mollenhauer B, Parnetti L, Chiasserini D, Molinuevo JL, Perret-Liaudet A, Verbeek MM, Andreasen N, Brosseron F, Bahl JM, Herukka SK, Hausner L, Frölich L, Labonte A, Poirier J, Miller AM, Zilka N, Kovacech B, Urbani A, Suardi S, Oliveira C, Baldeiras I, Dubois B, Rot U, Lehmann S, Skinningsrud A, Betsou F, Wiltfang J, Gkatzima O, Winblad B, Buchfelder M, Kornhuber J, Lewczuk P. Comparison of different matrices as potential quality control samples for neurochemical dementia diagnostics. J Alzheimers Dis. 2016;52:51–64.CrossRefPubMed Lelental N, Brandner S, Kofanova O, Blennow K, Zetterberg H, Andreasson U, Engelborghs S, Mroczko B, Gabryelewicz T, Teunissen C, Mollenhauer B, Parnetti L, Chiasserini D, Molinuevo JL, Perret-Liaudet A, Verbeek MM, Andreasen N, Brosseron F, Bahl JM, Herukka SK, Hausner L, Frölich L, Labonte A, Poirier J, Miller AM, Zilka N, Kovacech B, Urbani A, Suardi S, Oliveira C, Baldeiras I, Dubois B, Rot U, Lehmann S, Skinningsrud A, Betsou F, Wiltfang J, Gkatzima O, Winblad B, Buchfelder M, Kornhuber J, Lewczuk P. Comparison of different matrices as potential quality control samples for neurochemical dementia diagnostics. J Alzheimers Dis. 2016;52:51–64.CrossRefPubMed
18.
go back to reference Lewczuk P, Riederer P, O’Bryant SE, Verbeek MM, Dubois B, Visser PJ, Jellinger KJ, Engelborghs S, Ramirez A, Parnetti L, Jack Jr CR, Teunissen CE, Hampel H, Lleó A, Jessen F, Glodzik L, de Leon MJ, Fagan AM, Molinuevo JL, Jansen WJ, Winblad B, Shaw LM, Andreasson U, Otto M, Mollenhauer B, Wiltfang J, Turner MR, Zerr I, Handels R, Thompson AG, Johansson G, Ermann N, Trojanowski JQ, Karaca I, Wagner H, Oeckl P, van Waalwijk van Doorn L, Bjerke M, Kapogiannis D, Kuiperij HB, Farotti L, Li Y, Gordon BA, Epelbaum S, Vos SJB, Klijn CJM, Van Nostrand WE, Minguillon C, Schmitz M, Gallo C, Lopez Mato A, Thibaut F, Lista S, Alcolea D, Zetterberg D, Blennow K, Kornhuber J; Members of the WFSBP Task Force Working on this Topic: Riederer P, Gallo C, Kapogiannis D, Lopez Mato A, Thibaut F. Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: an update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry, World J Biol Psychiatry. 2017. https://doi.org/10.1080/15622975.2017.1375556. Lewczuk P, Riederer P, O’Bryant SE, Verbeek MM, Dubois B, Visser PJ, Jellinger KJ, Engelborghs S, Ramirez A, Parnetti L, Jack Jr CR, Teunissen CE, Hampel H, Lleó A, Jessen F, Glodzik L, de Leon MJ, Fagan AM, Molinuevo JL, Jansen WJ, Winblad B, Shaw LM, Andreasson U, Otto M, Mollenhauer B, Wiltfang J, Turner MR, Zerr I, Handels R, Thompson AG, Johansson G, Ermann N, Trojanowski JQ, Karaca I, Wagner H, Oeckl P, van Waalwijk van Doorn L, Bjerke M, Kapogiannis D, Kuiperij HB, Farotti L, Li Y, Gordon BA, Epelbaum S, Vos SJB, Klijn CJM, Van Nostrand WE, Minguillon C, Schmitz M, Gallo C, Lopez Mato A, Thibaut F, Lista S, Alcolea D, Zetterberg D, Blennow K, Kornhuber J; Members of the WFSBP Task Force Working on this Topic: Riederer P, Gallo C, Kapogiannis D, Lopez Mato A, Thibaut F. Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: an update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry, World J Biol Psychiatry. 2017. https://​doi.​org/​10.​1080/​15622975.​2017.​1375556.
19.
go back to reference Portelius E, Westman-Brinkmalm A, Zetterberg H, Blennow K. Determination of beta-amyloid peptide signatures in cerebrospinal fluid using immunoprecipitation-mass spectrometry. J Proteome Res. 2006;5:1010–6.CrossRefPubMed Portelius E, Westman-Brinkmalm A, Zetterberg H, Blennow K. Determination of beta-amyloid peptide signatures in cerebrospinal fluid using immunoprecipitation-mass spectrometry. J Proteome Res. 2006;5:1010–6.CrossRefPubMed
20.
go back to reference LaFerla FM, Green KN, Oddo S. Intracellular amyloid-beta in Alzheimer's disease. Nat Rev Neurosci. 2007;8:499–509.CrossRefPubMed LaFerla FM, Green KN, Oddo S. Intracellular amyloid-beta in Alzheimer's disease. Nat Rev Neurosci. 2007;8:499–509.CrossRefPubMed
21.
go back to reference Wiltfang J, Esselmann H, Bibl M, Hüll M, Hampel H, Kessler H, Frölich L, Schröder J, Peters O, Jessen F, Luckhaus C, Perneczky R, Jahn H, Fiszer M, Maler JM, Zimmermann R, Bruckmoser R, Kornhuber J, Lewczuk P. Amyloid beta peptide ratio 42/40 but not Aβ42 correlates with phospho-Tau in patients with low- and high-CSF Aβ40 load. J Neurochem. 2007;101:1053–9.CrossRefPubMed Wiltfang J, Esselmann H, Bibl M, Hüll M, Hampel H, Kessler H, Frölich L, Schröder J, Peters O, Jessen F, Luckhaus C, Perneczky R, Jahn H, Fiszer M, Maler JM, Zimmermann R, Bruckmoser R, Kornhuber J, Lewczuk P. Amyloid beta peptide ratio 42/40 but not Aβ42 correlates with phospho-Tau in patients with low- and high-CSF Aβ40 load. J Neurochem. 2007;101:1053–9.CrossRefPubMed
22.
go back to reference Baldeiras I, Santana I, Leitão MJ, Ribeiro MH, Pascoal R, Duro D, Lemos R, Santiago B, Almeida MR, Oliveira CR. Cerebrospinal fluid Aβ40 is similarly reduced in patients with frontotemporal lobar degeneration and Alzheimer's disease. J Neurol Sci. 2015;358:308–16.CrossRefPubMed Baldeiras I, Santana I, Leitão MJ, Ribeiro MH, Pascoal R, Duro D, Lemos R, Santiago B, Almeida MR, Oliveira CR. Cerebrospinal fluid Aβ40 is similarly reduced in patients with frontotemporal lobar degeneration and Alzheimer's disease. J Neurol Sci. 2015;358:308–16.CrossRefPubMed
23.
go back to reference Lewczuk P, Lelental N, Spitzer P, Maler JM, Kornhuber J. Amyloid-β 42/40 Cerebrospinal fluid concentration ratio in the diagnostics of Alzheimer's disease: validation of two novel assays. J Alzheimers Dis. 2015;43:183–91.PubMed Lewczuk P, Lelental N, Spitzer P, Maler JM, Kornhuber J. Amyloid-β 42/40 Cerebrospinal fluid concentration ratio in the diagnostics of Alzheimer's disease: validation of two novel assays. J Alzheimers Dis. 2015;43:183–91.PubMed
24.
go back to reference Lewczuk P, Esselmann H, Otto M, Maler JM, Henkel AW, Henkel MK, Eikenberg O, Antz C, Krause W-R, do Reulbach U, Kornhuber J, Wiltfang J. Neurochemical diagnosis of Alzheimer’s dementia by CSF Aβ42, Aβ42/Aβ40 ratio and total tau. Neurobiol Aging. 2004;25:273–81.CrossRefPubMed Lewczuk P, Esselmann H, Otto M, Maler JM, Henkel AW, Henkel MK, Eikenberg O, Antz C, Krause W-R, do Reulbach U, Kornhuber J, Wiltfang J. Neurochemical diagnosis of Alzheimer’s dementia by CSF Aβ42, Aβ42/Aβ40 ratio and total tau. Neurobiol Aging. 2004;25:273–81.CrossRefPubMed
25.
go back to reference Slaets S, Le Bastard N, Martin J-J, Sleegers K, Van Broeckhoven C, De Deyn PP, Engelborghs S. Cerebrospinal fluid Aβ1-40 improves differential dementia diagnosis in patients with intermediate P-tau181P levels. J Alzheimers Dis. 2013;36:759–67.PubMed Slaets S, Le Bastard N, Martin J-J, Sleegers K, Van Broeckhoven C, De Deyn PP, Engelborghs S. Cerebrospinal fluid Aβ1-40 improves differential dementia diagnosis in patients with intermediate P-tau181P levels. J Alzheimers Dis. 2013;36:759–67.PubMed
26.
go back to reference Janelidze S, Zetterberg H, Mattsson N, Palmqvist S, Vanderstichele H, Lindberg O, van Westen D, Stomrud E, Minthon E, Blennow K, for the Swedish BioFINDER study group, Hansson O. CSF Aβ42/Aβ40 and Aβ42/Aβ38 ratios: better diagnostic markers of Alzheimer disease. Ann Clin Transl Neurol. 2016;3:154–65.CrossRefPubMedPubMedCentral Janelidze S, Zetterberg H, Mattsson N, Palmqvist S, Vanderstichele H, Lindberg O, van Westen D, Stomrud E, Minthon E, Blennow K, for the Swedish BioFINDER study group, Hansson O. CSF Aβ42/Aβ40 and Aβ42/Aβ38 ratios: better diagnostic markers of Alzheimer disease. Ann Clin Transl Neurol. 2016;3:154–65.CrossRefPubMedPubMedCentral
27.
go back to reference Sauvée M, DidierLaurent G, Latarche C, Escanyé MC, Olivier JL, Malaplate-Armand C. Additional use of Aβ42/Aβ40 ratio with cerebrospinal fluid biomarkers P-Tau and Ab42 increases the level of evidence of Alzheimer’s disease pathophysiological process in routine practice. J Alzheimers Dis. 2014;41:377–86.PubMed Sauvée M, DidierLaurent G, Latarche C, Escanyé MC, Olivier JL, Malaplate-Armand C. Additional use of Aβ42/Aβ40 ratio with cerebrospinal fluid biomarkers P-Tau and Ab42 increases the level of evidence of Alzheimer’s disease pathophysiological process in routine practice. J Alzheimers Dis. 2014;41:377–86.PubMed
28.
go back to reference Dorey A, Perret-Liaudet A, Tholance Y, Fourie A, Quadrio I. Cerebrospinal fluid Aβ40 improves the interpretation of Aβ42 concentration for diagnosing Alzheimer’s disease. Front Neurol. 2015;6:247.CrossRefPubMedPubMedCentral Dorey A, Perret-Liaudet A, Tholance Y, Fourie A, Quadrio I. Cerebrospinal fluid Aβ40 improves the interpretation of Aβ42 concentration for diagnosing Alzheimer’s disease. Front Neurol. 2015;6:247.CrossRefPubMedPubMedCentral
29.
go back to reference Dumurgier J, Schraen S, Gabelle A, Vercruysse O, Bombois S, Laplanche JL, Peoc’h K, Sablonnière B, Kastanenka KV, Delaby C, Pasquier F, Touchon J, Hugon J, Paquet C, Lehmann S. Cerebrospinal fluid amyloid-β 42/40 ratio in clinical setting of memory centers: a multicentric study. Alzheimers Res Ther. 2015;7:30.CrossRefPubMedPubMedCentral Dumurgier J, Schraen S, Gabelle A, Vercruysse O, Bombois S, Laplanche JL, Peoc’h K, Sablonnière B, Kastanenka KV, Delaby C, Pasquier F, Touchon J, Hugon J, Paquet C, Lehmann S. Cerebrospinal fluid amyloid-β 42/40 ratio in clinical setting of memory centers: a multicentric study. Alzheimers Res Ther. 2015;7:30.CrossRefPubMedPubMedCentral
30.
go back to reference Lewczuk P, Matzen A, Blennow K, Parnetti L, Molinuevo JL, Eusebi P, Kornhuber J, Morris JC, Fagan AM. Cerebrospinal fluid Aβ42/40 corresponds better than Aβ42 to amyloid PET in Alzheimer’s disease. J Alzheimers Dis. 2017;55:813–22.CrossRefPubMed Lewczuk P, Matzen A, Blennow K, Parnetti L, Molinuevo JL, Eusebi P, Kornhuber J, Morris JC, Fagan AM. Cerebrospinal fluid Aβ42/40 corresponds better than Aβ42 to amyloid PET in Alzheimer’s disease. J Alzheimers Dis. 2017;55:813–22.CrossRefPubMed
31.
go back to reference Hansson O, Zetterberg H, Buchhave P, Andreasson U, Londos E, Minthon L, Blennow K. Prediction of Alzheimer’s Disease Using the CSF Aβ42/Aβ40 ratio in patients with mild cognitive impairment. Dement Geriatr Cogn Disord. 2007;23:316–20.CrossRefPubMed Hansson O, Zetterberg H, Buchhave P, Andreasson U, Londos E, Minthon L, Blennow K. Prediction of Alzheimer’s Disease Using the CSF Aβ42/Aβ40 ratio in patients with mild cognitive impairment. Dement Geriatr Cogn Disord. 2007;23:316–20.CrossRefPubMed
32.
go back to reference Parnetti L, Chiasserini D, Eusebi P, Giannandrea D, Bellomo G, De Carlo C, Padiglioni C, Mastrocola S, Lisetti V, Calabresi P. Performance of Aβ1-40, Aβ1-42, total Tau, and phosphorylated Tau as predictors of dementia in a cohort of patients with mild cognitive impairment. J Alzheimers Dis. 2012;29:229–38.PubMed Parnetti L, Chiasserini D, Eusebi P, Giannandrea D, Bellomo G, De Carlo C, Padiglioni C, Mastrocola S, Lisetti V, Calabresi P. Performance of Aβ1-40, Aβ1-42, total Tau, and phosphorylated Tau as predictors of dementia in a cohort of patients with mild cognitive impairment. J Alzheimers Dis. 2012;29:229–38.PubMed
33.
go back to reference Brys M, Pirraglia E, Rich K, Rolstad S, Mosconi L, Switalski R, Glodzik-Sobanska L, De Santi S, Zinkowski R, Mehta P, Pratico D, Saint Louis LA, Wallin A, Blennow K, de Leon MJ. Prediction and longitudinal study of CSF biomarkers in mild cognitive impairment. Neurobiol Aging. 2009;30:682–90.CrossRefPubMed Brys M, Pirraglia E, Rich K, Rolstad S, Mosconi L, Switalski R, Glodzik-Sobanska L, De Santi S, Zinkowski R, Mehta P, Pratico D, Saint Louis LA, Wallin A, Blennow K, de Leon MJ. Prediction and longitudinal study of CSF biomarkers in mild cognitive impairment. Neurobiol Aging. 2009;30:682–90.CrossRefPubMed
34.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
35.
go back to reference Petersen RC, Aisen P, Boeve BF, Geda YE, Ivnik RJ, Knopman DS, Mielke M, Pankratz VS, Roberts R, Rocca WA, Weigand S, Weiner M, Wiste H, Jack CR Jr. Mild cognitive impairment due to Alzheimer disease in the community. Ann Neurol. 2013;74:199–208.PubMedPubMedCentral Petersen RC, Aisen P, Boeve BF, Geda YE, Ivnik RJ, Knopman DS, Mielke M, Pankratz VS, Roberts R, Rocca WA, Weigand S, Weiner M, Wiste H, Jack CR Jr. Mild cognitive impairment due to Alzheimer disease in the community. Ann Neurol. 2013;74:199–208.PubMedPubMedCentral
36.
go back to reference Guo LH, Alexopoulos P, Eisele T, Wagenpfeil S, Kurz A, Perneczky R. The National Institute on Aging-Alzheimer's Association research criteria for mild cognitive impairment due to Alzheimer's disease: predicting the outcome. Eur Arch Psychiatry Clin Neurosci. 2013;263:325–33.CrossRefPubMed Guo LH, Alexopoulos P, Eisele T, Wagenpfeil S, Kurz A, Perneczky R. The National Institute on Aging-Alzheimer's Association research criteria for mild cognitive impairment due to Alzheimer's disease: predicting the outcome. Eur Arch Psychiatry Clin Neurosci. 2013;263:325–33.CrossRefPubMed
37.
go back to reference Duara R, Loewenstein DA, Shen Q, Barker W, Potter E, Varon D, Heurlin K, Vandenberghe R, Buckley C. Amyloid positron emission tomography with (18)F-flutemetamol and structural magnetic resonance imaging in the classification of mild cognitive impairment and Alzheimer's disease. Alzheimers Dement. 2013;9:295–301.CrossRefPubMed Duara R, Loewenstein DA, Shen Q, Barker W, Potter E, Varon D, Heurlin K, Vandenberghe R, Buckley C. Amyloid positron emission tomography with (18)F-flutemetamol and structural magnetic resonance imaging in the classification of mild cognitive impairment and Alzheimer's disease. Alzheimers Dement. 2013;9:295–301.CrossRefPubMed
38.
go back to reference Prestia A, Caroli A, van der Flier WM, Ossenkoppele R, Van Berckel B, Barkhof F, Teunissen CE, Wall AE, Carter SF, Schöll M, Choo IH, Nordberg A, Scheltens P, Frisoni GB. Prediction of dementia in MCI patients based on core diagnostic markers for Alzheimer disease. Neurology. 2013;80:1048–56.CrossRefPubMed Prestia A, Caroli A, van der Flier WM, Ossenkoppele R, Van Berckel B, Barkhof F, Teunissen CE, Wall AE, Carter SF, Schöll M, Choo IH, Nordberg A, Scheltens P, Frisoni GB. Prediction of dementia in MCI patients based on core diagnostic markers for Alzheimer disease. Neurology. 2013;80:1048–56.CrossRefPubMed
39.
go back to reference Vos SJ, Verhey F, Frölich L, Kornhuber J, Wiltfang J, Maier W, Peters O, Rüther E, Nobili F, Morbelli S, Frisoni GB, Drzezga A, Didic M, van Berckel BN, Simmons A, Soininen H, Kłoszewska I, Mecocci P, Tsolaki M, Vellas B, Lovestone S, Muscio C, Herukka SK, Salmon E, Bastin C, Wallin A, Nordlund A, de Mendonça A, Silva D, Santana I, Lemos R, Engelborghs S, Van der Mussele S, Alzheimer’s Disease Neuroimaging Initiative, Freund-Levi Y, Wallin ÅK, Hampel H, van der Flier W, Scheltens P, Visser PJ. Prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage. Brain. 2015;138:1327–38.CrossRefPubMedPubMedCentral Vos SJ, Verhey F, Frölich L, Kornhuber J, Wiltfang J, Maier W, Peters O, Rüther E, Nobili F, Morbelli S, Frisoni GB, Drzezga A, Didic M, van Berckel BN, Simmons A, Soininen H, Kłoszewska I, Mecocci P, Tsolaki M, Vellas B, Lovestone S, Muscio C, Herukka SK, Salmon E, Bastin C, Wallin A, Nordlund A, de Mendonça A, Silva D, Santana I, Lemos R, Engelborghs S, Van der Mussele S, Alzheimer’s Disease Neuroimaging Initiative, Freund-Levi Y, Wallin ÅK, Hampel H, van der Flier W, Scheltens P, Visser PJ. Prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage. Brain. 2015;138:1327–38.CrossRefPubMedPubMedCentral
40.
go back to reference Caroli A, Prestia A, Galluzzi S, Ferrari C, van der Flier WM, Ossenkoppele R, Van Berckel B, Barkhof F, Teunissen C, Wall AE, Carter SF, Schöll M, Choo IH, Grimmer T, Redolfi A, Nordberg A, Scheltens P, Drzezga A, Frisoni GB. Alzheimer's Disease Neuroimaging Initiative. Mild cognitive impairment with suspected nonamyloid pathology (SNAP): prediction of progression. Neurology. 2015;84:508–15.CrossRefPubMedPubMedCentral Caroli A, Prestia A, Galluzzi S, Ferrari C, van der Flier WM, Ossenkoppele R, Van Berckel B, Barkhof F, Teunissen C, Wall AE, Carter SF, Schöll M, Choo IH, Grimmer T, Redolfi A, Nordberg A, Scheltens P, Drzezga A, Frisoni GB. Alzheimer's Disease Neuroimaging Initiative. Mild cognitive impairment with suspected nonamyloid pathology (SNAP): prediction of progression. Neurology. 2015;84:508–15.CrossRefPubMedPubMedCentral
41.
go back to reference Bertens D, Knol DL, Scheltens P, Visser PJ. Alzheimer's Disease Neuroimaging Initiative. Temporal evolution of biomarkers and cognitive markers in the asymptomatic, MCI, and dementia stage of Alzheimer's disease. Alzheimers Dement. 2015;11:511–22.CrossRefPubMed Bertens D, Knol DL, Scheltens P, Visser PJ. Alzheimer's Disease Neuroimaging Initiative. Temporal evolution of biomarkers and cognitive markers in the asymptomatic, MCI, and dementia stage of Alzheimer's disease. Alzheimers Dement. 2015;11:511–22.CrossRefPubMed
42.
go back to reference Alexopoulos P, Werle L, Roesler J, Thierjung N, Gleixner LS, Yakushev I, Laskaris N, Wagenpfeil S, Gourzis P, Kurz A, Perneczky R, Alzheimer’s Disease Neuroimaging Initiative (ADNI). Conflicting cerebrospinal fluid biomarkers and progression to dementia due to Alzheimer's disease. Alzheimers Res Ther. 2016;8:51.CrossRefPubMedPubMedCentral Alexopoulos P, Werle L, Roesler J, Thierjung N, Gleixner LS, Yakushev I, Laskaris N, Wagenpfeil S, Gourzis P, Kurz A, Perneczky R, Alzheimer’s Disease Neuroimaging Initiative (ADNI). Conflicting cerebrospinal fluid biomarkers and progression to dementia due to Alzheimer's disease. Alzheimers Res Ther. 2016;8:51.CrossRefPubMedPubMedCentral
43.
go back to reference Baldeiras I, Santana I, Proenca MT, Garrucho MH, Pascoal R, Rodrigues A, Duro D, Oliveira CR. Oxidative damage and progression to Alzheimer's disease in patients with mild cognitive impairment. J Alzheimers Dis. 2010;21:1165–77.CrossRefPubMed Baldeiras I, Santana I, Proenca MT, Garrucho MH, Pascoal R, Rodrigues A, Duro D, Oliveira CR. Oxidative damage and progression to Alzheimer's disease in patients with mild cognitive impairment. J Alzheimers Dis. 2010;21:1165–77.CrossRefPubMed
44.
go back to reference Folstein MF, Folstein SE, McHugh PR. Mini-Mental State: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189–98.CrossRefPubMed Folstein MF, Folstein SE, McHugh PR. Mini-Mental State: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189–98.CrossRefPubMed
45.
go back to reference Guerreiro M, Silva AP, Botelho MA. Avaliação Breve do Estado Mental: Escalas e Testes na Demência. Lisbon: Grupo de Estudos de Envelhecimento Cerebral e Demência; 2003. p. 27–32. Guerreiro M, Silva AP, Botelho MA. Avaliação Breve do Estado Mental: Escalas e Testes na Demência. Lisbon: Grupo de Estudos de Envelhecimento Cerebral e Demência; 2003. p. 27–32.
46.
go back to reference Nasreddine Z, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53:695–9.CrossRefPubMed Nasreddine Z, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53:695–9.CrossRefPubMed
47.
go back to reference Simões MR, Freitas S, Santana I, Firmino H, Martins C, Nasreddine Z, Vilar M. Montreal Cognitive Assessment (MoCA): Versão final portuguesa. Coimbra: Serviço de Avaliação Psicológica, Faculdade de Psicologia e de Ciências da Educação da Universidade de Coimbra; 2008. Simões MR, Freitas S, Santana I, Firmino H, Martins C, Nasreddine Z, Vilar M. Montreal Cognitive Assessment (MoCA): Versão final portuguesa. Coimbra: Serviço de Avaliação Psicológica, Faculdade de Psicologia e de Ciências da Educação da Universidade de Coimbra; 2008.
48.
go back to reference Mohs RC, Rosen WG, Davis KL. The Alzheimer’s Disease Assessment Scale: an instrument for assessing treatment efficacy. Psychopharmacol Bull. 1983;19:448–50.PubMed Mohs RC, Rosen WG, Davis KL. The Alzheimer’s Disease Assessment Scale: an instrument for assessing treatment efficacy. Psychopharmacol Bull. 1983;19:448–50.PubMed
49.
go back to reference Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer’s Disease. Am J Psychiatry. 1984;141:1356–64.CrossRefPubMed Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer’s Disease. Am J Psychiatry. 1984;141:1356–64.CrossRefPubMed
50.
go back to reference Guerreiro M, Fonseca S, Barreto J. Escalas e Testes na Demência. Lisbon: Grupo de Estudos de Envelhecimento Cerebral e Demência; 2003. p. 33–49. Guerreiro M, Fonseca S, Barreto J. Escalas e Testes na Demência. Lisbon: Grupo de Estudos de Envelhecimento Cerebral e Demência; 2003. p. 33–49.
51.
go back to reference Guerreiro M. Contribution of neuropsychology to the study of dementias. PhD thesis. Lisbon: Faculty of Medicine of Lisbon; 1988. Guerreiro M. Contribution of neuropsychology to the study of dementias. PhD thesis. Lisbon: Faculty of Medicine of Lisbon; 1988.
52.
go back to reference Berg L. Clinical dementia rating (CDR). Psychopharmacol Bull. 1988;24:637–9.PubMed Berg L. Clinical dementia rating (CDR). Psychopharmacol Bull. 1988;24:637–9.PubMed
53.
go back to reference Gelinas I, Gauthier L, McIntyre M, Gauthier S. Development of a functional measure for persons with Alzheimer’s disease: the Disability Assessment for Dementia Scale. Am J Occup Ther. 1999;53:471–81.CrossRefPubMed Gelinas I, Gauthier L, McIntyre M, Gauthier S. Development of a functional measure for persons with Alzheimer’s disease: the Disability Assessment for Dementia Scale. Am J Occup Ther. 1999;53:471–81.CrossRefPubMed
54.
go back to reference Leitão O. Escalas e Testes na Demência. Lisbon: Grupo de Estudos de Envelhecimento Cerebral e Demência; 2008. p. 107–110. Leitão O. Escalas e Testes na Demência. Lisbon: Grupo de Estudos de Envelhecimento Cerebral e Demência; 2008. p. 107–110.
55.
go back to reference Cummings JL. The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology. 1997;48:10–6.CrossRef Cummings JL. The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology. 1997;48:10–6.CrossRef
56.
go back to reference Leitão O, Nina A. Escalas e Testes na Demência. Lisbon: Grupo de Estudos de Envelhecimento Cerebral e Demência; 2003. p. 67–86. Leitão O, Nina A. Escalas e Testes na Demência. Lisbon: Grupo de Estudos de Envelhecimento Cerebral e Demência; 2003. p. 67–86.
57.
go back to reference Petersen RC, Stevens JC, Ganguli M, Tangalos EG, Cummings JL, DeKosky ST. Practice parameter: early detection of dementia: mild cognitive impairment (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2001;56:1132–42.CrossRef Petersen RC, Stevens JC, Ganguli M, Tangalos EG, Cummings JL, DeKosky ST. Practice parameter: early detection of dementia: mild cognitive impairment (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2001;56:1132–42.CrossRef
58.
go back to reference Freitas S, Simões MR, Alves L, Santana I. Montreal Cognitive Assessment (MoCA): normative study for the Portuguese population. J Clin Exp Neuropsychol. 2011;33:989–96.CrossRefPubMed Freitas S, Simões MR, Alves L, Santana I. Montreal Cognitive Assessment (MoCA): normative study for the Portuguese population. J Clin Exp Neuropsychol. 2011;33:989–96.CrossRefPubMed
59.
go back to reference Roman GC, Tatemichi TK, Erkinjuntti T, Cummings JL, Masdeu JC, Garcia JH, Amaducci L, Orgogozo JM, Brun A, Hofman A, Moody DM, O’Brien MD, Yamaguchi T, Grafman J, Drayer BP, Bennett DA, Ficher M, Ogata J, Kokmen E, Bermejo F, Wolf PA, Gorelick PB, Bick KL, Pajeau AK, Bell MA, DeCarli C, Culebras A, Korczyn D, Bogousslavsky J, Hartmann A, Scheinberg P. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology. 1993;43:250–60.CrossRefPubMed Roman GC, Tatemichi TK, Erkinjuntti T, Cummings JL, Masdeu JC, Garcia JH, Amaducci L, Orgogozo JM, Brun A, Hofman A, Moody DM, O’Brien MD, Yamaguchi T, Grafman J, Drayer BP, Bennett DA, Ficher M, Ogata J, Kokmen E, Bermejo F, Wolf PA, Gorelick PB, Bick KL, Pajeau AK, Bell MA, DeCarli C, Culebras A, Korczyn D, Bogousslavsky J, Hartmann A, Scheinberg P. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology. 1993;43:250–60.CrossRefPubMed
60.
go back to reference Jack CR Jr, Knopman DS, Weigand SD, Wiste HJ, Vemuri P, Lowe V, Kantarci K, Gunter JL, Senjem ML, Ivnik RJ, Roberts RO, Rocca WA, Boeve BF, Petersen RC. An operational approach to National Institute on Aging-Alzheimer's Association criteria for preclinical Alzheimer disease. Ann Neurol. 2012;71:765–75.CrossRefPubMedPubMedCentral Jack CR Jr, Knopman DS, Weigand SD, Wiste HJ, Vemuri P, Lowe V, Kantarci K, Gunter JL, Senjem ML, Ivnik RJ, Roberts RO, Rocca WA, Boeve BF, Petersen RC. An operational approach to National Institute on Aging-Alzheimer's Association criteria for preclinical Alzheimer disease. Ann Neurol. 2012;71:765–75.CrossRefPubMedPubMedCentral
61.
go back to reference American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994.
62.
go back to reference McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. 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. 1984;4:939–44.CrossRef McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. 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. 1984;4:939–44.CrossRef
63.
go back to reference del Campo M, Mollenhauer B, Bertolotto A, Engelborghs S, Hampel H, Simonsen AH, Kapaki E, Kruse N, Le Bastard N, Lehmann S, Molinuevo JL, Parnetti L, Perret-Liaudet A, Sáez-Valero J, Saka E, Urbani A, Vanmechelen E, Verbeek M, Visser PJ, Teunissen C. Recommendations to standardize preanalytical confounding factors in Alzheimer's and Parkinson's disease cerebrospinal fluid biomarkers: an update. Biomark Med. 2012;6:419–30.CrossRefPubMed del Campo M, Mollenhauer B, Bertolotto A, Engelborghs S, Hampel H, Simonsen AH, Kapaki E, Kruse N, Le Bastard N, Lehmann S, Molinuevo JL, Parnetti L, Perret-Liaudet A, Sáez-Valero J, Saka E, Urbani A, Vanmechelen E, Verbeek M, Visser PJ, Teunissen C. Recommendations to standardize preanalytical confounding factors in Alzheimer's and Parkinson's disease cerebrospinal fluid biomarkers: an update. Biomark Med. 2012;6:419–30.CrossRefPubMed
64.
go back to reference Baldeiras I, Santana I, Garrucho MH, Pascoal R, Lemos R, Santiago B, Oliveira CR. CSF biomarkers for the early diagnosis of Alzheimer’s disease in a routine clinical setting—the first Portuguese study. Dermatol Sin. 2012;12:14–22. Baldeiras I, Santana I, Garrucho MH, Pascoal R, Lemos R, Santiago B, Oliveira CR. CSF biomarkers for the early diagnosis of Alzheimer’s disease in a routine clinical setting—the first Portuguese study. Dermatol Sin. 2012;12:14–22.
65.
go back to reference van Waalwijk van Doorn LJC, Kulic L, Koel-Simmelink MJA, Kuiperij HB, Versleijen AAM, Struyfs H, Twaalfhoven HAM, Fourier A, Engelborghs S, Perret-Liaudet A, Lehmann S, Verbeek MM, Vanmechelen EJM, Teunissen CE. Multicenter analytical validation of Aβ40 immunoassays. Front Neurol. 2017;8:310.CrossRefPubMedPubMedCentral van Waalwijk van Doorn LJC, Kulic L, Koel-Simmelink MJA, Kuiperij HB, Versleijen AAM, Struyfs H, Twaalfhoven HAM, Fourier A, Engelborghs S, Perret-Liaudet A, Lehmann S, Verbeek MM, Vanmechelen EJM, Teunissen CE. Multicenter analytical validation of Aβ40 immunoassays. Front Neurol. 2017;8:310.CrossRefPubMedPubMedCentral
66.
go back to reference 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, Lladó 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, Schröder 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. The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers. Alzheimers Dement. 2011;7:386–95.CrossRefPubMedPubMedCentral 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, Lladó 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, Schröder 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. The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers. Alzheimers Dement. 2011;7:386–95.CrossRefPubMedPubMedCentral
67.
go back to reference Crook R, Hardy J, Duff K. Single-day apolipoprotein E genotyping. J Neurosci Methods. 1994;53:125–7.CrossRefPubMed Crook R, Hardy J, Duff K. Single-day apolipoprotein E genotyping. J Neurosci Methods. 1994;53:125–7.CrossRefPubMed
68.
go back to reference Hanley JA, McNeil BJ. A method of comparing the areas under receiver operating characteristic curves. Radiology. 1983;148:839–43.CrossRefPubMed Hanley JA, McNeil BJ. A method of comparing the areas under receiver operating characteristic curves. Radiology. 1983;148:839–43.CrossRefPubMed
69.
go back to reference Gabriel AJ, Almeida MR, Ribeiro MH, Durães J, Tábuas-Pereira M, Pinheiro AC, Pascoal R, Santana I, Baldeiras I. Association between butyrylcholinesterase and cerebrospinal fluid biomarkers in Alzheimer’s disease patients. Neurosci Lett. 2017;641:101–6.CrossRefPubMed Gabriel AJ, Almeida MR, Ribeiro MH, Durães J, Tábuas-Pereira M, Pinheiro AC, Pascoal R, Santana I, Baldeiras I. Association between butyrylcholinesterase and cerebrospinal fluid biomarkers in Alzheimer’s disease patients. Neurosci Lett. 2017;641:101–6.CrossRefPubMed
70.
go back to reference Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, Moher D, Rennie D, de Vet HC, Lijmer JG. The STARD statement for reporting studies of diagnostic accuracy: explanation and elaboration. Clin Chem. 2003;49:718. Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, Moher D, Rennie D, de Vet HC, Lijmer JG. The STARD statement for reporting studies of diagnostic accuracy: explanation and elaboration. Clin Chem. 2003;49:718.
71.
go back to reference Struyfs H, Van Broeck B, Timmers M, Fransen E, Sleegers K, Van Broeckhoven C, De Deyn PP, Streffer JR, Mercken M, Engelborghs S. Diagnostic accuracy of cerebrospinal fluid amyloid-β isoforms for early and differential dementia diagnosis. J Alzheimers Dis. 2015;45:813–22.PubMed Struyfs H, Van Broeck B, Timmers M, Fransen E, Sleegers K, Van Broeckhoven C, De Deyn PP, Streffer JR, Mercken M, Engelborghs S. Diagnostic accuracy of cerebrospinal fluid amyloid-β isoforms for early and differential dementia diagnosis. J Alzheimers Dis. 2015;45:813–22.PubMed
72.
go back to reference Kester MI, Scheffer PG, Koel-Simmelink MJ, Twaalfhoven H, Verwey NA, Veerhuis R, Twisk JW, Bouwman FH, Blankenstein MA, Scheltens P, Teunissen C, van der Flier WM. Serial CSF sampling in Alzheimer's disease: specific versus non-specific markers. Neurobiol Aging. 2012;33:1591–8.CrossRefPubMed Kester MI, Scheffer PG, Koel-Simmelink MJ, Twaalfhoven H, Verwey NA, Veerhuis R, Twisk JW, Bouwman FH, Blankenstein MA, Scheltens P, Teunissen C, van der Flier WM. Serial CSF sampling in Alzheimer's disease: specific versus non-specific markers. Neurobiol Aging. 2012;33:1591–8.CrossRefPubMed
73.
go back to reference Gervaise-Henry C, Watfa G, Albuisson E, Kolodziej A, Dousset B, Olivier JL, Jonveaux TR, Malaplate-Armand C. Cerebrospinal fluid Aβ42/Aβ40 as a means to limiting tube- and storage-dependent pre-analytical variability in clinical setting. J Alzheimers Dis. 2017;57:437–55.CrossRefPubMed Gervaise-Henry C, Watfa G, Albuisson E, Kolodziej A, Dousset B, Olivier JL, Jonveaux TR, Malaplate-Armand C. Cerebrospinal fluid Aβ42/Aβ40 as a means to limiting tube- and storage-dependent pre-analytical variability in clinical setting. J Alzheimers Dis. 2017;57:437–55.CrossRefPubMed
74.
go back to reference Lewczuk P, Beck G, Esselmann H, Bruckmoser R, Zimmermann R, Fiszer M, Bibl M, Maler JM, Kornhuber J, Wiltfang J. Effect of sample collection tubes on cerebrospinal fluid concentrations of tau proteins and amyloid beta peptides. Clin Chem. 2006;52:332–4.CrossRefPubMed Lewczuk P, Beck G, Esselmann H, Bruckmoser R, Zimmermann R, Fiszer M, Bibl M, Maler JM, Kornhuber J, Wiltfang J. Effect of sample collection tubes on cerebrospinal fluid concentrations of tau proteins and amyloid beta peptides. Clin Chem. 2006;52:332–4.CrossRefPubMed
75.
go back to reference Slemmon JR, Shapiro A, Mercken M, Streffer J, Romano G, Andreasen N, Zetterberg H, Blennow K. Impact of cerebrospinal fluid matrix on the detection of Alzheimer’s disease with Aβ42 and influence of disease on the total- Aβ42/Aβ40 ratio. J Neurochem. 2015;135:1049–58.CrossRefPubMed Slemmon JR, Shapiro A, Mercken M, Streffer J, Romano G, Andreasen N, Zetterberg H, Blennow K. Impact of cerebrospinal fluid matrix on the detection of Alzheimer’s disease with Aβ42 and influence of disease on the total- Aβ42/Aβ40 ratio. J Neurochem. 2015;135:1049–58.CrossRefPubMed
77.
go back to reference Zimmermann R, Lelental N, Ganslandt O, Maler JM, Kornhuber J, Lewczuk P. Preanalytical sample handling and sample stability testing for the neurochemical dementia diagnostics. J Alzheimers Dis. 2011;25:739–45.PubMed Zimmermann R, Lelental N, Ganslandt O, Maler JM, Kornhuber J, Lewczuk P. Preanalytical sample handling and sample stability testing for the neurochemical dementia diagnostics. J Alzheimers Dis. 2011;25:739–45.PubMed
78.
go back to reference Schipke CG, Jessen F, Teipel S, Luckhaus C, Wiltfang J, Esselmann H, Frölich L, Maier W, Rüther E, Heppner FL, Prokop S, Heuser I, Peters O. Long-term stability of Alzheimer's disease biomarker proteins in cerebrospinal fluid. J Alzheimers Dis. 2011;26:255–62.PubMed Schipke CG, Jessen F, Teipel S, Luckhaus C, Wiltfang J, Esselmann H, Frölich L, Maier W, Rüther E, Heppner FL, Prokop S, Heuser I, Peters O. Long-term stability of Alzheimer's disease biomarker proteins in cerebrospinal fluid. J Alzheimers Dis. 2011;26:255–62.PubMed
79.
go back to reference Willemse E, van Uffelen K, Brix B, Engelborghs S, Vanderstichele H, Teunissen C. How to handle adsorption of cerebrospinal fluid amyloid β (1-42) in laboratory practice? Identifying problematic handlings and resolving the issue by use of the Aβ42/Aβ40 ratio. Alzheimers Dement. 2017;13:885–92.CrossRefPubMed Willemse E, van Uffelen K, Brix B, Engelborghs S, Vanderstichele H, Teunissen C. How to handle adsorption of cerebrospinal fluid amyloid β (1-42) in laboratory practice? Identifying problematic handlings and resolving the issue by use of the Aβ42/Aβ40 ratio. Alzheimers Dement. 2017;13:885–92.CrossRefPubMed
Metadata
Title
Addition of the Aβ42/40 ratio to the cerebrospinal fluid biomarker profile increases the predictive value for underlying Alzheimer’s disease dementia in mild cognitive impairment
Authors
Inês Baldeiras
Isabel Santana
Maria João Leitão
Helena Gens
Rui Pascoal
Miguel Tábuas-Pereira
José Beato-Coelho
Diana Duro
Maria Rosário Almeida
Catarina Resende Oliveira
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 1/2018
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/s13195-018-0362-2

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