Wolfsgruber, Steffen, Luis Molinuevo, Jose, Wagner, Michael ORCID: 0000-0003-2589-6440, Teunissen, Charlotte E., Rami, Lorena, Coll-Padros, Nina ORCID: 0000-0002-9282-6701, Bouwman, Femke H., Slot, Rosalinde E. R., Wesselman, Linda M. P., Peters, Oliver, Luther, Katja, Buerger, Katharina, Priller, Josef ORCID: 0000-0001-7596-0979, Laske, Christoph, Teipel, Stefan, Spottke, Annika, Heneka, Michael T., Duezel, Emrah, Drzezga, Alexander, Wiltfang, Jens ORCID: 0000-0003-1492-5330, Sikkes, Sietske A. M., van der Flier, Wiesje M. and Jessen, Frank (2019). 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., 11. LONDON: BMC. ISSN 1758-9193

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Abstract

IntroductionSubjective 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).MethodsWe 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 (A)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.ResultsThe prevalence of abnormal A42, 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 A42 (and also abnormal tau or ptau181) levels was predicted by age and APOE status. For A42 abnormality, we additionally observed a center effect, indicating between-center heterogeneity not explained by age, APOE, or the other included covariates.ConclusionsWhile heterogeneous frequency of abnormal A42 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Wolfsgruber, SteffenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Luis Molinuevo, JoseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagner, MichaelUNSPECIFIEDorcid.org/0000-0003-2589-6440UNSPECIFIED
Teunissen, Charlotte E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rami, LorenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Coll-Padros, NinaUNSPECIFIEDorcid.org/0000-0002-9282-6701UNSPECIFIED
Bouwman, Femke H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Slot, Rosalinde E. R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wesselman, Linda M. P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peters, OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Luther, KatjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buerger, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Priller, JosefUNSPECIFIEDorcid.org/0000-0001-7596-0979UNSPECIFIED
Laske, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Teipel, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spottke, AnnikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heneka, Michael T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Duezel, EmrahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Drzezga, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wiltfang, JensUNSPECIFIEDorcid.org/0000-0003-1492-5330UNSPECIFIED
Sikkes, Sietske A. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van der Flier, Wiesje M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jessen, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-159126
DOI: 10.1186/s13195-018-0463-y
Journal or Publication Title: Alzheimers Res. Ther.
Volume: 11
Date: 2019
Publisher: BMC
Place of Publication: LONDON
ISSN: 1758-9193
Language: English
Faculty: Faculty of Management, Economy and Social Sciences
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CEREBROSPINAL-FLUID BIOMARKERS; OLDER-ADULTS; IMPAIRMENT; VALIDATION; PREVENTION; FRAMEWORK; TRIALS; RISK; CAREMultiple languages
Clinical Neurology; NeurosciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/15912

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