Department of Neurodegeneration and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.
German Center for Neurodegenerative Diseases, Sigmund-Freud-Straße 27, 53127, Bonn, Germany.
Alzheimers Res Ther. 2019 Jan 17;11(1):8. doi: 10.1186/s13195-018-0463-y.
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.
简介:认知正常的老年人出现主观认知能力下降(SCD),已被认为是阿尔茨海默病(AD)痴呆的早期临床高危状态,也是未来痴呆预防试验的目标人群。然而,目前 SCD 在研究中的定义存在异质性,可能导致 AD 病理的患病率存在差异。在这里,我们比较了三个参与欧洲临床前 AD 中 SCD 协调倡议(Euro-SCD)的欧洲记忆诊所中 SCD 患者的异常 AD 生物标志物的患病率和共同决定因素。 方法:我们纳入了三个有可用脑脊液(CSF)生物标志物的记忆诊所 SCD 样本(巴塞罗那 IDIBAPS,西班牙,n=44;阿姆斯特丹痴呆队列(ADC),荷兰,n=50;德国 DELCODE 多中心研究,n=42)。使用阿姆斯特丹的预设界值对 CSF 生物标志物(β淀粉样蛋白(Aβ)42、tau 和磷酸化 tau(ptau181))进行集中分析,以定义病理性生物标志物浓度的患病率。我们使用三个中心的综合样本进行逻辑回归分析,以调查中心效应与生物标志物异常的可能性,同时考虑到潜在的共同预测因素(例如,年龄、性别、载脂蛋白 E(APOE)状态、轻微认知缺陷、抑郁症状)。 结果:异常 Aβ42 水平的患病率在各中心之间存在差异,但 tau 或 ptau181 水平的患病率无差异(DELCODE 为 64%,IDIBAPS 为 57%,ADC 为 22%;p<0.001)。逻辑回归分析表明,异常 Aβ42(以及异常 tau 或 ptau181)水平的可能性由年龄和 APOE 状态预测。对于 Aβ42 异常,我们还观察到中心效应,表明中心之间存在异质性,无法用年龄、APOE 或其他纳入的协变量来解释。 结论:虽然异常 Aβ42 的频率存在差异,部分原因是样本之间的年龄范围和 APOE 状态存在差异,但中心效应的额外观察表明中心之间存在异质性,这可能归因于不同的招募程序。这些发现强调需要制定协调一致的 SCD 病例定义招募方案,以实现跨国研究中类似的临床前 AD 富集率。
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