Multimorbidity patterns and blood biomarkers of Alzheimer's disease in community-dwelling cognitively unimpaired older adults

IF 13 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2025-06-22 DOI:10.1002/alz.70411

Alessandra Marengoni, Giulia Grande, Martina Valletta, Caterina Gregorio, Amaia Calderón-Larrañaga, Matilda Dale, Claudia Fredolini, Bengt Winblad, Davide Liborio Vetrano

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Abstract

INTRODUCTION

Alzheimer's disease (AD) blood biomarkers hold clinical potential but their concentration may vary with somatic conditions.

METHODS

We investigated the concentration of six AD blood biomarkers in relation to multimorbidity as disease count and four multimorbidity patterns in 2290 cognitively unimpaired older adults.

RESULTS

Levels of phosphorylated tau (p-tau)181, p-tau217, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) increased with increasing number of diseases. In multi-adjusted regressions, compared to individuals without multimorbidity, the anemia/sensory impairment pattern was associated with altered levels of all biomarkers except amyloid beta (Aβ)42/40, GFAP, and total tau (p-tau181: β = 0.18, 95% confidence interval [CI]: 0.08, 0.28; p-tau217: β = 0.11, 95% CI: 0.03, 0.18; NfL: β = 0.14, 95% CI: 0.06, 0.21) and the cardiometabolic/inflammatory pattern was associated with altered levels of all biomarkers except Aβ42/40 and GFAP (p-tau181: β = 0.24, 95% CI: 0.12, 0.36; p-tau217: β = 0.23, 95% CI: 0.14, 0.32; NfL: β = 0.32, 95% CI: 0.23, 0.40; total tau: β = 0.23, 95% CI: 0.07, 0.39). Results remained unchanged after excluding those who developed dementia in 15 years.

DISCUSSION

More diseases and specific multimorbidity patterns altered the levels of several AD blood biomarkers, highlighting caution when using them in adults with complex health profiles.

Highlights

In cognitively unimpaired older adults blood biomarkers of Alzheimer's disease varied depending on the number of chronic diseases and specific patterns of multimorbidity.
Phosphorylated tau (p-tau)181, p-tau217, neurofilament light chain (NfL), and glial fibrillary acidic protein levels increased along with increasing numbers of chronic diseases.
P-tau181, p-tau217, and NfL levels were significantly higher in individuals in the anemia/sensory impairment and cardiometabolic/inflammatory multimorbidity patterns compared to those without multimorbidity.
Results remained unchanged after excluding participants who developed dementia during 15-year follow-up.

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社区居住认知功能未受损老年人阿尔茨海默病的多发病模式和血液生物标志物

阿尔茨海默病（AD）血液生物标志物具有临床潜力，但其浓度可能随躯体状况而变化。方法研究了2290名认知功能未受损的老年人中6种AD血液生物标志物的浓度与疾病数量和4种多发病模式的关系。结果磷酸化tau (p-tau)181、p-tau217、神经丝轻链（NfL）和胶质纤维酸性蛋白（GFAP）水平随着疾病数量的增加而升高。在多重校正回归中，与没有多重发病的个体相比，贫血/感觉障碍模式与所有生物标志物水平的改变有关，除了淀粉样蛋白β (Aβ)42/40、GFAP和总tau蛋白(p-tau181: β = 0.18, 95%可信区间[CI]: 0.08, 0.28；p-tau217: β = 0.11, 95% CI: 0.03, 0.18；NfL: β = 0.14, 95% CI: 0.06, 0.21)，心脏代谢/炎症模式与除Aβ42/40和GFAP外的所有生物标志物水平的改变相关(p-tau181: β = 0.24, 95% CI: 0.12, 0.36；p-tau217: β = 0.23, 95% CI: 0.14, 0.32；NfL: β = 0.32, 95% CI: 0.23, 0.40；总tau: β = 0.23, 95% CI: 0.07, 0.39)。排除那些在15年内患上痴呆症的人后，结果没有变化。更多的疾病和特定的多发病模式改变了几种AD血液生物标志物的水平，强调在具有复杂健康状况的成年人中使用它们时要谨慎。在认知功能未受损的老年人中，阿尔茨海默病的血液生物标志物根据慢性疾病的数量和多病的特定模式而变化。磷酸化tau (p-tau)181、p-tau217、神经丝轻链（NfL）和胶质原纤维酸性蛋白水平随着慢性疾病数量的增加而增加。P-tau181、p-tau217和NfL水平在贫血/感觉障碍和心脏代谢/炎症多重发病模式的个体中显著高于无多重发病的个体。排除在15年随访期间发生痴呆的参与者后，结果保持不变。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.