Márquez Freddie, Tarraf Wassim, Gonzalez Kevin, Valencia Deisha F, Stickel Ariana M, Anita Natasha Z, Sotres-Alvarez Daniela, Levin Bonnie E, Yassa Michael A, Zhou Haibo, Daviglus Martha, Pirzada Amber, Goodman Zachary T, Thyagarajan Bharat, Gallo Linda C, González Hector M
Department of Neurosciences, University of California, San Diego, La Jolla.
Institute of Gerontology and Department of Healthcare Sciences, Wayne State University, Detroit, Michigan.
JAMA Netw Open. 2025 Sep 2;8(9):e2531038. doi: 10.1001/jamanetworkopen.2025.31038.
Subjective cognitive decline (SCD) may be an early indicator of Alzheimer disease and related dementias (ADRD), yet its association with plasma biomarkers remains unclear among middle-aged and older adults (aged 50-86 years).
To examine associations between plasma biomarkers of amyloid, tau, neuroaxonal damage, and glial activation with SCD in a heterogeneous cohort of Hispanic and/or Latino adults.
DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used survey-weighted data from the Study of Latinos-Investigation of Neurocognitive Aging, an ancillary study of the Hispanic Community Health Study/Study of Latinos. Participants were aged 50 to 86 years and resided in 4 major US cities. Data were collected from 2016 to 2018 and analyzed between December 2024 and June 2025.
Plasma biomarkers included amyloid-beta (Aβ42/40), phosphorylated tau-181 (ptau-181), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP), quantified using Simoa (Quanterix HD-X) and log-transformed (ln) to reduce skewness.
SCD was assessed using the short-form Everyday Cognition Scale (ECog-12), evaluating global-, executive-, and memory-related SCD, and a single-item cognitive concerns question. Survey-weighted linear and logistic regression models tested associations between biomarkers and SCD, adjusting for demographic, cardiovascular, kidney, and APOE genotype covariates.
Among 5712 adults (mean [SD] age, 63.47 (8.15) years; unweighted 3663 [53.92%] female), higher ln(ptau-181) was associated with ECog-12 memory (unstandardized β = 0.088; 95% CI, 0.005-0.170). Higher ln(NfL) levels were associated with greater ECog-12 global (unstandardized β = 0.169; 95% CI, 0.074-0.265), executive (unstandardized β = 0.182; 95% CI, 0.087-0.277), and memory (unstandardized β = 0.156; 95% CI, 0.065-0.248) domains. Higher ln(GFAP) levels were associated with greater ECog-12 global (unstandardized β = 0.109; 95% CI, 0.019-0.198) and executive (unstandardized β = 0.121; 95% CI, 0.031-0.211) domains. Ln(Aβ42/40) was not associated with SCD domains. Cognitive concerns significantly modified the associations between ln(NfL) and ECog-12 domains, with more pronounced associations among those reporting cognitive concerns. No biomarkers were associated with the single-item cognitive concerns score.
In this study of middle-aged and older Hispanic and/or Latino adults, plasma biomarkers of p-tau181, NfL, and GFAP, but not Aβ42/40, were associated with greater SCD. These findings underscore their potential utility in early ADRD detection strategies.
主观认知衰退（SCD）可能是阿尔茨海默病及相关痴呆症（ADRD）的早期指标，但在中年及老年成年人（50 - 86岁）中，其与血浆生物标志物之间的关联仍不明确。
在西班牙裔和/或拉丁裔成年人的异质队列中，研究淀粉样蛋白、tau蛋白、神经轴突损伤和神经胶质细胞激活的血浆生物标志物与SCD之间的关联。
设计、背景和参与者：这项横断面研究使用了来自拉丁裔神经认知衰老研究（拉丁裔社区健康研究/拉丁裔研究的一项辅助研究）的调查加权数据。参与者年龄在50至86岁之间，居住在美国4个主要城市。数据于2016年至2018年收集，并于2024年12月至2025年6月进行分析。
血浆生物标志物包括淀粉样β蛋白（Aβ42/40）、磷酸化tau - 181（ptau - 181）、神经丝轻链（NfL）和胶质纤维酸性蛋白（GFAP），使用Simoa（Quanterix HD - X）进行定量，并进行对数转换（ln）以减少偏态。
使用简化版日常认知量表（ECog - 12）评估SCD，评估整体、执行和记忆相关的SCD，以及一个单项认知问题。调查加权线性和逻辑回归模型测试生物标志物与SCD之间的关联，并对人口统计学、心血管、肾脏和APOE基因型协变量进行调整。
在5712名成年人中（平均[标准差]年龄为63.47（8.15）岁；未加权时3663名[53.92%]为女性），较高的ln(ptau - 181)与ECog - 12记忆相关（未标准化β = 0.088；95%置信区间，0.005 - 0.170）。较高的ln(NfL)水平与更大的ECog - 12整体（未标准化β = 0.
