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

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  • dc.contributor.author Wolfsgruber, Steffen
  • dc.contributor.author Molinuevo, José Luis
  • dc.contributor.author Euro-SCD working group
  • dc.date.accessioned 2020-05-22T07:34:29Z
  • dc.date.available 2020-05-22T07:34:29Z
  • dc.date.issued 2019
  • dc.description.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.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Wolfsgruber S, Molinuevo JL, Wagner M, Teunissen CE, Rami L, Coll-Padrós N et al. Prevalence of abnormal Alzheimer's disease biomarkers in patients with subjective cognitive decline: cross-sectional comparison of three European memory clinic samples. Alzheimers Res Ther. 2019; 11(1):8. DOI: 10.1186/s13195-018-0463-y
  • dc.identifier.doi http://dx.doi.org/10.1186/s13195-018-0463-y
  • dc.identifier.issn 1758-9193
  • dc.identifier.uri http://hdl.handle.net/10230/44644
  • dc.language.iso eng
  • dc.publisher BioMed Central
  • dc.relation.ispartof Alzheimers Res Ther. 2019; 11(1):8
  • dc.rights © The Author(s). 2019 Open Access This 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.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword CSF biomarkers
  • dc.subject.keyword Preclinical Alzheimer’s disease
  • dc.subject.keyword Subjective cognitive decline
  • dc.title Prevalence of abnormal Alzheimer's disease biomarkers in patients with subjective cognitive decline: cross-sectional comparison of three European memory clinic samples
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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