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Alzheimers Res Ther. 2019 Jan 17;11(1):8. doi: 10.1186/s13195-018-0463-y.

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

Author information

1
Department of Neurodegeneration and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany. Steffen.Wolfsgruber@dzne.de.
2
German Center for Neurodegenerative Diseases, Sigmund-Freud-Straße 27, 53127, Bonn, Germany. Steffen.Wolfsgruber@dzne.de.
3
Alzheimer's Disease and Other Cognitive Disorders Unit, IDIBAPS, Hospital Clinic, Barcelona, Spain.
4
BarcelonaBeta Brain Research Center, Fundació Pasqual Maragall, Pompeu Fabra University, Barcelona, Spain.
5
Department of Neurodegeneration and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.
6
German Center for Neurodegenerative Diseases, Sigmund-Freud-Straße 27, 53127, Bonn, Germany.
7
Neurochemistry Lab and Biobank, Department of Clinical Chemistry, Amsterdam Neuroscience, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
8
Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
9
Department of Psychiatry and Psychotherapy, Charité, Campus Benjamin Franklin, Berlin, Germany.
10
Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany.
11
German Center for Neurodegenerative Diseases, Munich, Germany.
12
Department of Neuropsychiatry, Charité-Universitaetsmedizin Berlin, Berlin, Germany.
13
Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany.
14
German Center for Neurodegenerative Diseases, Tübingen, Germany.
15
German Center for Neurodegenerative Diseases, Rostock, Germany.
16
German Center for Neurodegenerative Diseases, Magdeburg, Germany.
17
Department of Nuclear Medicine, Medical Faculty, University of Cologne, Cologne, Germany.
18
German Center for Neurodegenerative Diseases (DZNE), Goettingen, Germany.
19
Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Goettingen, Germany.
20
iBiMED, Medical Sciences Department, University of Aveiro, Aveiro, Portugal.
21
Department of Epidemiology and Biostatistics, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
22
Massachusetts General Hospital, Department of Neurology / Harvard Medical School, Boston, USA.
23
Department of Psychiatry, Medical Faculty, University of Cologne, Cologne, Germany.

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.

KEYWORDS:

CSF biomarkers; Preclinical Alzheimer’s disease; Subjective cognitive decline

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