Improved Cerebrospinal Fluid-Based Discrimination between Alzheimer's Disease Patients and Controls after Correction for Ventricular Volumes

Linda J. C. van Waalwijk van Doorn; Juan D. Gispert; H. Bea Kuiperij; Jurgen A. H. R. Claassen; Andrea Arighi; Ines Baldeiras; Kaj Blennow; Marco Bozzali; Miguel Castelo-Branco; Enrica Cavedo; Derya D. Emek-Savas; Erden Eren; Paolo Eusebi; Lucia Farotti; Chiara Fenoglio; Juan Fortea Ormaechea; Yvonne Freund-Levi; Giovanni B. Frisoni; Daniela Galimberti; Sermin Genc; Viviana Greco; Harald Hampel; Sanna-Kaisa Herukka; Yawu Liu; Albert Llado; Alberto Lleo; Flavio M. Nobili; Kader K. Oguz; Lucilla Parnetti; Joao Pereira; Agnese Picco; Maria Pikkarainen; Catarina Resende de Oliveira; Esen Saka; Nicola Salvadori; Raquel Sanchez-Valle; Isabel Santana; Elio Scarpini; Philip Scheltens; Hilkka Soininen; Roberto Tarducci; Charlotte Teunissen; Magda Tsolaki; Andrea Urbani; Eduard Vilaplana; Pieter Jelle Visser; Asa K. Wallin; Gorsev Yener; Jose L. Molinuevo; Olga Meulenbroek; Marcel M. Verbeek

doi:10.3233/JAD-160668

Improved Cerebrospinal Fluid-Based Discrimination between Alzheimer's Disease Patients and Controls after Correction for Ventricular Volumes

Linda J. C. van Waalwijk van Doorn, Juan D. Gispert, H. Bea Kuiperij, Jurgen A. H. R. Claassen, Andrea Arighi, Ines Baldeiras, Kaj Blennow, Marco Bozzali, Miguel Castelo-Branco, Enrica Cavedo, Derya D. Emek-Savas, Erden Eren, Paolo Eusebi, Lucia Farotti, Chiara Fenoglio, Juan Fortea Ormaechea, Yvonne Freund-Levi, Giovanni B. Frisoni, Daniela Galimberti, Sermin GencViviana Greco, Harald Hampel, Sanna-Kaisa Herukka, Yawu Liu, Albert Llado, Alberto Lleo, Flavio M. Nobili, Kader K. Oguz, Lucilla Parnetti, Joao Pereira, Agnese Picco, Maria Pikkarainen, Catarina Resende de Oliveira, Esen Saka, Nicola Salvadori, Raquel Sanchez-Valle, Isabel Santana, Elio Scarpini, Philip Scheltens, Hilkka Soininen, Roberto Tarducci, Charlotte Teunissen, Magda Tsolaki, Andrea Urbani, Eduard Vilaplana, Pieter Jelle Visser, Asa K. Wallin, Gorsev Yener, Jose L. Molinuevo, Olga Meulenbroek, Marcel M. Verbeek^*

^*Corresponding author for this work

MHeNs - Cognitive Neuropsychiatry and Clinical Neuroscience

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Cerebrospinal fluid (CSF) biomarkers may support the diagnosis of Alzheimer's disease (AD). We studied if the diagnostic power of AD CSF biomarker concentrations, i.e., A beta(42), total tau (t-tau), and phosphorylated tau (p-tau), is affected by differences in lateral ventricular volume (VV), using CSF biomarker data and magnetic resonance imaging (MRI) scans of 730 subjects, from 13 European Memory Clinics. We developed a Matlab-algorithm for standardized automated segmentation analysis of T1 weighted MRI scans in SPM8 for determining VV, and computed its ratio with total intracranial volume (TIV) as proxy for total CSF volume. The diagnostic power of CSF biomarkers (and their combination), either corrected for VV/TIV ratio or not, was determined by ROC analysis. CSF A beta(42) levels inversely correlated to VV/TIV in the whole study population (A beta(42): r = -0.28; p <0.0001). For CSF t-tau and p-tau, this association only reached statistical significance in the combined MCI and AD group (t-tau: r = -0.15; p-tau: r = -0.13; both p <0.01). Correction for differences in VV/TIV improved the differentiation of AD versus controls based on CSF A beta(42) alone (AUC: 0.75 versus 0.81) or in combination with t-tau (AUC: 0.81 versus 0.91). In conclusion, differences in VV may be an important confounder in interpreting CSF A beta(42) levels.

Original language	English
Pages (from-to)	543-555
Number of pages	13
Journal	Journal of Alzheimer's Disease
Volume	56
Issue number	2
DOIs	https://doi.org/10.3233/JAD-160668
Publication status	Published - 2017

Keywords

Alzheimer's disease
amyloid biomarkers
cerebrospinal fluid
lateral ventricles
tau protein
MILD COGNITIVE IMPAIRMENT
AD-CSF-INDEX
NATIONAL INSTITUTE
ASSOCIATION WORKGROUPS
DIAGNOSTIC GUIDELINES
BRAIN ATROPHY
BIOMARKERS
DEMENTIA
RECOMMENDATIONS
TAU

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10.3233/JAD-160668

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van Doorn, L. J. C. V. W., Gispert, J. D., Kuiperij, H. B., Claassen, J. A. H. R., Arighi, A., Baldeiras, I., Blennow, K., Bozzali, M., Castelo-Branco, M., Cavedo, E., Emek-Savas, D. D., Eren, E., Eusebi, P., Farotti, L., Fenoglio, C., Ormaechea, J. F., Freund-Levi, Y., Frisoni, G. B., Galimberti, D., ... Verbeek, M. M. (2017). Improved Cerebrospinal Fluid-Based Discrimination between Alzheimer's Disease Patients and Controls after Correction for Ventricular Volumes. Journal of Alzheimer's Disease, 56(2), 543-555. https://doi.org/10.3233/JAD-160668

@article{905bd87426c7444b80be56a60ad75740,

title = "Improved Cerebrospinal Fluid-Based Discrimination between Alzheimer's Disease Patients and Controls after Correction for Ventricular Volumes",

abstract = "Cerebrospinal fluid (CSF) biomarkers may support the diagnosis of Alzheimer's disease (AD). We studied if the diagnostic power of AD CSF biomarker concentrations, i.e., A beta(42), total tau (t-tau), and phosphorylated tau (p-tau), is affected by differences in lateral ventricular volume (VV), using CSF biomarker data and magnetic resonance imaging (MRI) scans of 730 subjects, from 13 European Memory Clinics. We developed a Matlab-algorithm for standardized automated segmentation analysis of T1 weighted MRI scans in SPM8 for determining VV, and computed its ratio with total intracranial volume (TIV) as proxy for total CSF volume. The diagnostic power of CSF biomarkers (and their combination), either corrected for VV/TIV ratio or not, was determined by ROC analysis. CSF A beta(42) levels inversely correlated to VV/TIV in the whole study population (A beta(42): r = -0.28; p <0.0001). For CSF t-tau and p-tau, this association only reached statistical significance in the combined MCI and AD group (t-tau: r = -0.15; p-tau: r = -0.13; both p <0.01). Correction for differences in VV/TIV improved the differentiation of AD versus controls based on CSF A beta(42) alone (AUC: 0.75 versus 0.81) or in combination with t-tau (AUC: 0.81 versus 0.91). In conclusion, differences in VV may be an important confounder in interpreting CSF A beta(42) levels.",

keywords = "Alzheimer's disease, amyloid biomarkers, cerebrospinal fluid, lateral ventricles, tau protein, MILD COGNITIVE IMPAIRMENT, AD-CSF-INDEX, NATIONAL INSTITUTE, ASSOCIATION WORKGROUPS, DIAGNOSTIC GUIDELINES, BRAIN ATROPHY, BIOMARKERS, DEMENTIA, RECOMMENDATIONS, TAU",

author = "{van Doorn}, {Linda J. C. van Waalwijk} and Gispert, {Juan D.} and Kuiperij, {H. Bea} and Claassen, {Jurgen A. H. R.} and Andrea Arighi and Ines Baldeiras and Kaj Blennow and Marco Bozzali and Miguel Castelo-Branco and Enrica Cavedo and Emek-Savas, {Derya D.} and Erden Eren and Paolo Eusebi and Lucia Farotti and Chiara Fenoglio and Ormaechea, {Juan Fortea} and Yvonne Freund-Levi and Frisoni, {Giovanni B.} and Daniela Galimberti and Sermin Genc and Viviana Greco and Harald Hampel and Sanna-Kaisa Herukka and Yawu Liu and Albert Llado and Alberto Lleo and Nobili, {Flavio M.} and Oguz, {Kader K.} and Lucilla Parnetti and Joao Pereira and Agnese Picco and Maria Pikkarainen and {de Oliveira}, {Catarina Resende} and Esen Saka and Nicola Salvadori and Raquel Sanchez-Valle and Isabel Santana and Elio Scarpini and Philip Scheltens and Hilkka Soininen and Roberto Tarducci and Charlotte Teunissen and Magda Tsolaki and Andrea Urbani and Eduard Vilaplana and Visser, {Pieter Jelle} and Wallin, {Asa K.} and Gorsev Yener and Molinuevo, {Jose L.} and Olga Meulenbroek and Verbeek, {Marcel M.}",

year = "2017",

doi = "10.3233/JAD-160668",

language = "English",

volume = "56",

pages = "543--555",

journal = "Journal of Alzheimer's Disease",

issn = "1387-2877",

publisher = "SAGE Publications Ltd",

number = "2",

}

van Doorn, LJCVW, Gispert, JD, Kuiperij, HB, Claassen, JAHR, Arighi, A, Baldeiras, I, Blennow, K, Bozzali, M, Castelo-Branco, M, Cavedo, E, Emek-Savas, DD, Eren, E, Eusebi, P, Farotti, L, Fenoglio, C, Ormaechea, JF, Freund-Levi, Y, Frisoni, GB, Galimberti, D, Genc, S, Greco, V, Hampel, H, Herukka, S-K, Liu, Y, Llado, A, Lleo, A, Nobili, FM, Oguz, KK, Parnetti, L, Pereira, J, Picco, A, Pikkarainen, M, de Oliveira, CR, Saka, E, Salvadori, N, Sanchez-Valle, R, Santana, I, Scarpini, E, Scheltens, P, Soininen, H, Tarducci, R, Teunissen, C, Tsolaki, M, Urbani, A, Vilaplana, E, Visser, PJ, Wallin, AK, Yener, G, Molinuevo, JL, Meulenbroek, O & Verbeek, MM 2017, 'Improved Cerebrospinal Fluid-Based Discrimination between Alzheimer's Disease Patients and Controls after Correction for Ventricular Volumes', Journal of Alzheimer's Disease, vol. 56, no. 2, pp. 543-555. https://doi.org/10.3233/JAD-160668

Improved Cerebrospinal Fluid-Based Discrimination between Alzheimer's Disease Patients and Controls after Correction for Ventricular Volumes. / van Doorn, Linda J. C. van Waalwijk; Gispert, Juan D.; Kuiperij, H. Bea et al.
In: Journal of Alzheimer's Disease, Vol. 56, No. 2, 2017, p. 543-555.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Improved Cerebrospinal Fluid-Based Discrimination between Alzheimer's Disease Patients and Controls after Correction for Ventricular Volumes

AU - van Doorn, Linda J. C. van Waalwijk

AU - Gispert, Juan D.

AU - Kuiperij, H. Bea

AU - Claassen, Jurgen A. H. R.

AU - Arighi, Andrea

AU - Baldeiras, Ines

AU - Blennow, Kaj

AU - Bozzali, Marco

AU - Castelo-Branco, Miguel

AU - Cavedo, Enrica

AU - Emek-Savas, Derya D.

AU - Eren, Erden

AU - Eusebi, Paolo

AU - Farotti, Lucia

AU - Fenoglio, Chiara

AU - Ormaechea, Juan Fortea

AU - Freund-Levi, Yvonne

AU - Frisoni, Giovanni B.

AU - Galimberti, Daniela

AU - Genc, Sermin

AU - Greco, Viviana

AU - Hampel, Harald

AU - Herukka, Sanna-Kaisa

AU - Liu, Yawu

AU - Llado, Albert

AU - Lleo, Alberto

AU - Nobili, Flavio M.

AU - Oguz, Kader K.

AU - Parnetti, Lucilla

AU - Pereira, Joao

AU - Picco, Agnese

AU - Pikkarainen, Maria

AU - de Oliveira, Catarina Resende

AU - Saka, Esen

AU - Salvadori, Nicola

AU - Sanchez-Valle, Raquel

AU - Santana, Isabel

AU - Scarpini, Elio

AU - Scheltens, Philip

AU - Soininen, Hilkka

AU - Tarducci, Roberto

AU - Teunissen, Charlotte

AU - Tsolaki, Magda

AU - Urbani, Andrea

AU - Vilaplana, Eduard

AU - Visser, Pieter Jelle

AU - Wallin, Asa K.

AU - Yener, Gorsev

AU - Molinuevo, Jose L.

AU - Meulenbroek, Olga

AU - Verbeek, Marcel M.

PY - 2017

Y1 - 2017

N2 - Cerebrospinal fluid (CSF) biomarkers may support the diagnosis of Alzheimer's disease (AD). We studied if the diagnostic power of AD CSF biomarker concentrations, i.e., A beta(42), total tau (t-tau), and phosphorylated tau (p-tau), is affected by differences in lateral ventricular volume (VV), using CSF biomarker data and magnetic resonance imaging (MRI) scans of 730 subjects, from 13 European Memory Clinics. We developed a Matlab-algorithm for standardized automated segmentation analysis of T1 weighted MRI scans in SPM8 for determining VV, and computed its ratio with total intracranial volume (TIV) as proxy for total CSF volume. The diagnostic power of CSF biomarkers (and their combination), either corrected for VV/TIV ratio or not, was determined by ROC analysis. CSF A beta(42) levels inversely correlated to VV/TIV in the whole study population (A beta(42): r = -0.28; p <0.0001). For CSF t-tau and p-tau, this association only reached statistical significance in the combined MCI and AD group (t-tau: r = -0.15; p-tau: r = -0.13; both p <0.01). Correction for differences in VV/TIV improved the differentiation of AD versus controls based on CSF A beta(42) alone (AUC: 0.75 versus 0.81) or in combination with t-tau (AUC: 0.81 versus 0.91). In conclusion, differences in VV may be an important confounder in interpreting CSF A beta(42) levels.

AB - Cerebrospinal fluid (CSF) biomarkers may support the diagnosis of Alzheimer's disease (AD). We studied if the diagnostic power of AD CSF biomarker concentrations, i.e., A beta(42), total tau (t-tau), and phosphorylated tau (p-tau), is affected by differences in lateral ventricular volume (VV), using CSF biomarker data and magnetic resonance imaging (MRI) scans of 730 subjects, from 13 European Memory Clinics. We developed a Matlab-algorithm for standardized automated segmentation analysis of T1 weighted MRI scans in SPM8 for determining VV, and computed its ratio with total intracranial volume (TIV) as proxy for total CSF volume. The diagnostic power of CSF biomarkers (and their combination), either corrected for VV/TIV ratio or not, was determined by ROC analysis. CSF A beta(42) levels inversely correlated to VV/TIV in the whole study population (A beta(42): r = -0.28; p <0.0001). For CSF t-tau and p-tau, this association only reached statistical significance in the combined MCI and AD group (t-tau: r = -0.15; p-tau: r = -0.13; both p <0.01). Correction for differences in VV/TIV improved the differentiation of AD versus controls based on CSF A beta(42) alone (AUC: 0.75 versus 0.81) or in combination with t-tau (AUC: 0.81 versus 0.91). In conclusion, differences in VV may be an important confounder in interpreting CSF A beta(42) levels.

KW - Alzheimer's disease

KW - amyloid biomarkers

KW - cerebrospinal fluid

KW - lateral ventricles

KW - tau protein

KW - MILD COGNITIVE IMPAIRMENT

KW - AD-CSF-INDEX

KW - NATIONAL INSTITUTE

KW - ASSOCIATION WORKGROUPS

KW - DIAGNOSTIC GUIDELINES

KW - BRAIN ATROPHY

KW - BIOMARKERS

KW - DEMENTIA

KW - RECOMMENDATIONS

KW - TAU

U2 - 10.3233/JAD-160668

DO - 10.3233/JAD-160668

M3 - Article

C2 - 28059783

SN - 1387-2877

VL - 56

SP - 543

EP - 555

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

IS - 2

ER -

Improved Cerebrospinal Fluid-Based Discrimination between Alzheimer's Disease Patients and Controls after Correction for Ventricular Volumes

Abstract

Keywords

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