Prevalence of abnormal Alzheimer's disease biomarkers in patients with subjective cognitive decline: Cross-sectional comparison of three European memory clinic samples Jose Luis Molinuevo (jlmolinuevo@barcelonabeta.org); Frank Jessen (frank.jessen@uk-koeln.de); Wiesje Van der Flier (WM.vdFlier@vumc.nl)

Steffen Wolfsgruber, José Luis Molinuevo, Michael Wagner, Charlotte E. Teunissen, Lorena Rami, Nina Coll-Padrós, Femke H. Bouwman, Rosalinde E. R. Slot, Linda M. P. Wesselman, Oliver Peters, Katja Luther, Katharina Buerger, Josef Priller, Christoph Laske, Stefan Teipel, Annika Spottke, Michael T. Heneka, Emrah Düzel, Alexander Drzezga, Jens Wiltfang & 3 others Sietske A. M. Sikkes, Wiesje M. van der Flier, Frank Jessen

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.
Original languageEnglish
Article number8
JournalAlzheimer's Research and Therapy
Volume11
Issue number1
DOIs
Publication statusPublished - 2019

Cite this

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 Jose Luis Molinuevo (jlmolinuevo@barcelonabeta.org); Frank Jessen (frank.jessen@uk-koeln.de); Wiesje Van der Flier (WM.vdFlier@vumc.nl). In: Alzheimer's Research and Therapy. 2019 ; Vol. 11, No. 1.
@article{9b040b063e354915a76477896333c09b,
title = "Prevalence of abnormal Alzheimer's disease biomarkers in patients with subjective cognitive decline: Cross-sectional comparison of three European memory clinic samples Jose Luis Molinuevo (jlmolinuevo@barcelonabeta.org); Frank Jessen (frank.jessen@uk-koeln.de); Wiesje Van der Flier (WM.vdFlier@vumc.nl)",
abstract = "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.",
author = "Steffen Wolfsgruber and Molinuevo, {Jos{\'e} Luis} and Michael Wagner and Teunissen, {Charlotte E.} and Lorena Rami and Nina Coll-Padr{\'o}s and Bouwman, {Femke H.} and Slot, {Rosalinde E. R.} and Wesselman, {Linda M. P.} and Oliver Peters and Katja Luther and Katharina Buerger and Josef Priller and Christoph Laske and Stefan Teipel and Annika Spottke and Heneka, {Michael T.} and Emrah D{\"u}zel and Alexander Drzezga and Jens Wiltfang and Sikkes, {Sietske A. M.} and {van der Flier}, {Wiesje M.} and Frank Jessen",
year = "2019",
doi = "10.1186/s13195-018-0463-y",
language = "English",
volume = "11",
journal = "Alzheimer's Research & Therapy",
issn = "1758-9193",
publisher = "BioMed Central",
number = "1",

}

Prevalence of abnormal Alzheimer's disease biomarkers in patients with subjective cognitive decline: Cross-sectional comparison of three European memory clinic samples Jose Luis Molinuevo (jlmolinuevo@barcelonabeta.org); Frank Jessen (frank.jessen@uk-koeln.de); Wiesje Van der Flier (WM.vdFlier@vumc.nl). / 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.

In: Alzheimer's Research and Therapy, Vol. 11, No. 1, 8, 2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Prevalence of abnormal Alzheimer's disease biomarkers in patients with subjective cognitive decline: Cross-sectional comparison of three European memory clinic samples Jose Luis Molinuevo (jlmolinuevo@barcelonabeta.org); Frank Jessen (frank.jessen@uk-koeln.de); Wiesje Van der Flier (WM.vdFlier@vumc.nl)

AU - Wolfsgruber, Steffen

AU - Molinuevo, José Luis

AU - Wagner, Michael

AU - Teunissen, Charlotte E.

AU - Rami, Lorena

AU - Coll-Padrós, Nina

AU - Bouwman, Femke H.

AU - Slot, Rosalinde E. R.

AU - Wesselman, Linda M. P.

AU - Peters, Oliver

AU - Luther, Katja

AU - Buerger, Katharina

AU - Priller, Josef

AU - Laske, Christoph

AU - Teipel, Stefan

AU - Spottke, Annika

AU - Heneka, Michael T.

AU - Düzel, Emrah

AU - Drzezga, Alexander

AU - Wiltfang, Jens

AU - Sikkes, Sietske A. M.

AU - van der Flier, Wiesje M.

AU - Jessen, Frank

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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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UR - https://www.ncbi.nlm.nih.gov/pubmed/30654834

U2 - 10.1186/s13195-018-0463-y

DO - 10.1186/s13195-018-0463-y

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VL - 11

JO - Alzheimer's Research & Therapy

JF - Alzheimer's Research & Therapy

SN - 1758-9193

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