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

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 (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.ResultsThe 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.ConclusionsWhile 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.

Association of serum apolipoprotein B with cerebrospinal fluid biomarkers of Alzheimer’s disease pathology in elderly adults with subjective cognitive decline

“…Results showed that, compared with the CN subgroup, although there was no significant cognitive decline, there were obvious changes in CSF AD core biomarkers (especially Aβ-related biomarkers) in the SCD subgroup, which were consistent with previous studies (8,27). In fact, accumulating cross-sectional or longitudinal evidence has supported that SCD occurred at the preclinical stage of AD and might serve as a symptomatic indicator of preclinical AD (7,8,(27)(28)(29)(30)(31)(32)(33). Our analysis of population characteristics showed that, in our study, SCD participants had preclinical AD characteristics.…”

“…Subjective cognitive decline (SCD) in individuals without objective cognitive impairment was recognized as a transitional stage between a fully asymptomatic stage and a mild cognitively impaired (MCI) stage of the disease (7,8). It has been suggested to be a possible first symptomatic expression of preclinical AD and a target stage for future AD prevention trials.…”

Association of plasma apolipoprotein B with cerebrospinal fluid Alzheimer’s disease biomarkers in patients with subjective cognitive decline

“…This study is the first to systematically explore cross-sectional associations of CSF AD core biomarkers with ApoB, ApoA1, and First of all, we analyzed the characteristics of SCD participants included in our study. Results showed that, compared with the CN subgroup, although there was no significant cognitive decline, there were obvious changes in CSF AD core biomarkers (especially Aβ-related biomarkers) in the SCD subgroup, which were consistent with previous studies [8,24]. In fact, accumulating cross-sectional or longitudinal evidence has supported that SCD Finally we detailed the associations of ApoB, ApoA1, and ApoB/A1 with CSF AD core biomarkers in total participants or different diagnostic subgroups and analyzed the factors that might affect these associations.…”

Subjective cognitive decline and subsequent dementia: a nationwide cohort study of 579,710 people aged 66 years in South Korea

“…It has been demonstrated that AD biomarkers such as cerebrospinal fluid β-amyloid [39,40], plasma β-amyloid [41], hippocampal atrophy [41], and amyloid retention in positron emission tomography [42] are associated with SCD. Although the prevalence of AD pathology in SCD may differ between memory centres due to their varied study designs [43], SCD might be an early symptom in the preclinical stage of AD. Previous studies have reported inconsistent results regarding the association between SCD and non-AD dementia, such as vascular dementia, Lewy body dementia, and frontotemporal lobar degeneration [8,10].…”