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Prevalence of abnormal Alzheimer’s disease biomarkers in patients with subjective cognitive decline: cross-sectional comparison of three European memory clinic samples

INTRODUCTION: Subjective cognitive decline (SCD) in cognitively unimpaired older individuals has been recognized as an early clinical at-risk state for Alzheimer’s disease (AD) dementia and as a target population for future dementia prevention trials. Currently, however, SCD is heterogeneously defin...

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Autores principales: Wolfsgruber, Steffen, Molinuevo, José Luis, Wagner, Michael, Teunissen, Charlotte E., Rami, Lorena, Coll-Padrós, Nina, Bouwman, Femke H., Slot, Rosalinde E. R., Wesselman, Linda M. P., Peters, Oliver, Luther, Katja, Buerger, Katharina, Priller, Josef, Laske, Christoph, Teipel, Stefan, Spottke, Annika, Heneka, Michael T., Düzel, Emrah, Drzezga, Alexander, Wiltfang, Jens, Sikkes, Sietske A. M., van der Flier, Wiesje M., Jessen, Frank
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337830/
https://www.ncbi.nlm.nih.gov/pubmed/30654834
http://dx.doi.org/10.1186/s13195-018-0463-y
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author Wolfsgruber, Steffen
Molinuevo, José Luis
Wagner, Michael
Teunissen, Charlotte E.
Rami, Lorena
Coll-Padrós, Nina
Bouwman, Femke H.
Slot, Rosalinde E. R.
Wesselman, Linda M. P.
Peters, Oliver
Luther, Katja
Buerger, Katharina
Priller, Josef
Laske, Christoph
Teipel, Stefan
Spottke, Annika
Heneka, Michael T.
Düzel, Emrah
Drzezga, Alexander
Wiltfang, Jens
Sikkes, Sietske A. M.
van der Flier, Wiesje M.
Jessen, Frank
author_facet Wolfsgruber, Steffen
Molinuevo, José Luis
Wagner, Michael
Teunissen, Charlotte E.
Rami, Lorena
Coll-Padrós, Nina
Bouwman, Femke H.
Slot, Rosalinde E. R.
Wesselman, Linda M. P.
Peters, Oliver
Luther, Katja
Buerger, Katharina
Priller, Josef
Laske, Christoph
Teipel, Stefan
Spottke, Annika
Heneka, Michael T.
Düzel, Emrah
Drzezga, Alexander
Wiltfang, Jens
Sikkes, Sietske A. M.
van der Flier, Wiesje M.
Jessen, Frank
author_sort Wolfsgruber, Steffen
collection PubMed
description INTRODUCTION: Subjective cognitive decline (SCD) in cognitively unimpaired older individuals has been recognized as an early clinical at-risk state for Alzheimer’s disease (AD) dementia and as a target population for future dementia prevention trials. Currently, however, SCD is heterogeneously defined across studies, potentially leading to variations in the prevalence of AD pathology. Here, we compared the prevalence and identified common determinants of abnormal AD biomarkers in SCD across three European memory clinics participating in the European initiative on harmonization of SCD in preclinical AD (Euro-SCD). METHODS: We included three memory clinic SCD samples with available cerebrospinal fluid (CSF) biomaterial (IDIBAPS, Barcelona, Spain, n = 44; Amsterdam Dementia Cohort (ADC), The Netherlands, n = 50; DELCODE multicenter study, Germany, n = 42). CSF biomarkers (amyloid beta (Aβ)42, tau, and phosphorylated tau (ptau181)) were centrally analyzed in Amsterdam using prespecified cutoffs to define prevalence of pathological biomarker concentrations. We used logistic regression analysis in the combined sample across the three centers to investigate center effects with regard to likelihood of biomarker abnormality while taking potential common predictors (e.g., age, sex, apolipoprotein E (APOE) status, subtle cognitive deficits, depressive symptoms) into account. RESULTS: The prevalence of abnormal Aβ42, but not tau or ptau181, levels was different across centers (64% DELCODE, 57% IDIBAPS, 22% ADC; p < 0.001). Logistic regression analysis revealed that the likelihood of abnormal Aβ42 (and also abnormal tau or ptau181) levels was predicted by age and APOE status. For Aβ42 abnormality, we additionally observed a center effect, indicating between-center heterogeneity not explained by age, APOE, or the other included covariates. CONCLUSIONS: While heterogeneous frequency of abnormal Aβ42 was partly explained by between-sample differences in age range and APOE status, the additional observation of center effects indicates between-center heterogeneity that may be attributed to different recruitment procedures. These findings highlight the need for the development of harmonized recruitment protocols for SCD case definition in multinational studies to achieve similar enrichment rates of preclinical AD.
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spelling pubmed-63378302019-01-23 Prevalence of abnormal Alzheimer’s disease biomarkers in patients with subjective cognitive decline: cross-sectional comparison of three European memory clinic samples Wolfsgruber, Steffen Molinuevo, José Luis Wagner, Michael Teunissen, Charlotte E. Rami, Lorena Coll-Padrós, Nina Bouwman, Femke H. Slot, Rosalinde E. R. Wesselman, Linda M. P. Peters, Oliver Luther, Katja Buerger, Katharina Priller, Josef Laske, Christoph Teipel, Stefan Spottke, Annika Heneka, Michael T. Düzel, Emrah Drzezga, Alexander Wiltfang, Jens Sikkes, Sietske A. M. van der Flier, Wiesje M. Jessen, Frank Alzheimers Res Ther Research INTRODUCTION: Subjective cognitive decline (SCD) in cognitively unimpaired older individuals has been recognized as an early clinical at-risk state for Alzheimer’s disease (AD) dementia and as a target population for future dementia prevention trials. Currently, however, SCD is heterogeneously defined across studies, potentially leading to variations in the prevalence of AD pathology. Here, we compared the prevalence and identified common determinants of abnormal AD biomarkers in SCD across three European memory clinics participating in the European initiative on harmonization of SCD in preclinical AD (Euro-SCD). METHODS: We included three memory clinic SCD samples with available cerebrospinal fluid (CSF) biomaterial (IDIBAPS, Barcelona, Spain, n = 44; Amsterdam Dementia Cohort (ADC), The Netherlands, n = 50; DELCODE multicenter study, Germany, n = 42). CSF biomarkers (amyloid beta (Aβ)42, tau, and phosphorylated tau (ptau181)) were centrally analyzed in Amsterdam using prespecified cutoffs to define prevalence of pathological biomarker concentrations. We used logistic regression analysis in the combined sample across the three centers to investigate center effects with regard to likelihood of biomarker abnormality while taking potential common predictors (e.g., age, sex, apolipoprotein E (APOE) status, subtle cognitive deficits, depressive symptoms) into account. RESULTS: The prevalence of abnormal Aβ42, but not tau or ptau181, levels was different across centers (64% DELCODE, 57% IDIBAPS, 22% ADC; p < 0.001). Logistic regression analysis revealed that the likelihood of abnormal Aβ42 (and also abnormal tau or ptau181) levels was predicted by age and APOE status. For Aβ42 abnormality, we additionally observed a center effect, indicating between-center heterogeneity not explained by age, APOE, or the other included covariates. CONCLUSIONS: While heterogeneous frequency of abnormal Aβ42 was partly explained by between-sample differences in age range and APOE status, the additional observation of center effects indicates between-center heterogeneity that may be attributed to different recruitment procedures. These findings highlight the need for the development of harmonized recruitment protocols for SCD case definition in multinational studies to achieve similar enrichment rates of preclinical AD. BioMed Central 2019-01-17 /pmc/articles/PMC6337830/ /pubmed/30654834 http://dx.doi.org/10.1186/s13195-018-0463-y Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Wolfsgruber, Steffen
Molinuevo, José Luis
Wagner, Michael
Teunissen, Charlotte E.
Rami, Lorena
Coll-Padrós, Nina
Bouwman, Femke H.
Slot, Rosalinde E. R.
Wesselman, Linda M. P.
Peters, Oliver
Luther, Katja
Buerger, Katharina
Priller, Josef
Laske, Christoph
Teipel, Stefan
Spottke, Annika
Heneka, Michael T.
Düzel, Emrah
Drzezga, Alexander
Wiltfang, Jens
Sikkes, Sietske A. M.
van der Flier, Wiesje M.
Jessen, Frank
Prevalence of abnormal Alzheimer’s disease biomarkers in patients with subjective cognitive decline: cross-sectional comparison of three European memory clinic samples
title Prevalence of abnormal Alzheimer’s disease biomarkers in patients with subjective cognitive decline: cross-sectional comparison of three European memory clinic samples
title_full Prevalence of abnormal Alzheimer’s disease biomarkers in patients with subjective cognitive decline: cross-sectional comparison of three European memory clinic samples
title_fullStr Prevalence of abnormal Alzheimer’s disease biomarkers in patients with subjective cognitive decline: cross-sectional comparison of three European memory clinic samples
title_full_unstemmed Prevalence of abnormal Alzheimer’s disease biomarkers in patients with subjective cognitive decline: cross-sectional comparison of three European memory clinic samples
title_short Prevalence of abnormal Alzheimer’s disease biomarkers in patients with subjective cognitive decline: cross-sectional comparison of three European memory clinic samples
title_sort prevalence of abnormal alzheimer’s disease biomarkers in patients with subjective cognitive decline: cross-sectional comparison of three european memory clinic samples
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337830/
https://www.ncbi.nlm.nih.gov/pubmed/30654834
http://dx.doi.org/10.1186/s13195-018-0463-y
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