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

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.

Fig. 1

Boxplots for cerebrospinal fluid (CSF) levels in each sample of the three participating Euro-SCD centers. Values are presented in pg/ml. Points mark individual values lying outside 1.5 times the interquartile range (25–75% percentile). Asterisks mark extreme values lying outside three times the interquartile range. ^#The DELCODE and IDIBAPS sample show significantly lower levels compared with the ADC sample (p < 0.001). ADC Amsterdam Dementia Cohort, DELCODE German Center for Neurodegenerative Diseases (DZNE) multicenter Longitudinal Cognitive Impairment and Dementia Study, IDIBAPS l’Institut d’Investigacions Biomèdiques August Pi i Sunyer Hospital Clinic Barcelona