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生物和神经影像学标志物可预测老年人 5 年内发生体弱:MAPT 研究的二次分析。

Biological and Neuroimaging Markers as Predictors of 5-Year Incident Frailty in Older Adults: A Secondary Analysis of the MAPT Study.

机构信息

Gerontopole of Toulouse, Institute of Ageing, Toulouse University Hospital (CHU Toulouse), France.

UPS/Inserm UMR1027, University of Toulouse III, France.

出版信息

J Gerontol A Biol Sci Med Sci. 2021 Oct 13;76(11):e361-e369. doi: 10.1093/gerona/glaa296.

Abstract

BACKGROUND

This study aims to investigate the predictive value of biological and neuroimaging markers to determine incident frailty among older people for a period of 5 years.

METHODS

We included 1394 adults aged 70 years and older from the Multidomain Alzheimer Preventive Trial, who were not frail at baseline (according to Fried's criteria) and who had at least 1 post-baseline measurement of frailty. Participants who progressed to frailty during the 5-year follow-up were categorized as "incident frailty" and those who remained non-frail were categorized as "without frailty." The differences of baseline biochemical factors (25-hydroxyvitamin D, homocysteine, omega-3 index, C-reactive protein), other biological markers (Apolipoprotein E genotypes, amyloid-β deposits), and neuroimaging data (gray matter volume, hippocampal volume, white matter hyperintensities) were compared between groups. Cox proportional hazard model was used to evaluate the associations between biomarkers and incident frailty.

RESULTS

A total of 195 participants (14.0%) became frail over 5 years. Although 25-hydroxyvitamin D deficiency, homocysteine levels, low-grade inflammation (persistently increased C-reactive protein 3-10 mg/L), gray matter, and hippocampal volume were significantly associated with incident frailty in unadjusted models, these associations disappeared after adjustment for age, sex, and other confounders. Omega-3 index was the sole marker that presented a trend of association with incident frailty (hazard ratio: 0.92; 95% confidence interval: 0.83-1.01; p = .082).

CONCLUSIONS

This study failed to identify biomarkers able to predict frailty incidence in community-dwelling older adults for a period of 5 years. Further longitudinal research with multiple measurements of biomarkers and frailty is needed to evaluate the long-term relationships between changes in biomarkers levels and frailty evolution.

摘要

背景

本研究旨在探讨生物和神经影像学标志物的预测价值,以确定 5 年内老年人发生虚弱的情况。

方法

我们纳入了来自多领域阿尔茨海默病预防试验的 1394 名年龄在 70 岁及以上的成年人,他们在基线时(根据 Fried 的标准)没有虚弱,并且至少有 1 次基线后虚弱的测量。在 5 年随访期间进展为虚弱的参与者被归类为“发生虚弱”,而那些保持非虚弱的参与者被归类为“无虚弱”。比较了两组间基线生化因素(25-羟维生素 D、同型半胱氨酸、ω-3 指数、C 反应蛋白)、其他生物学标志物(载脂蛋白 E 基因型、淀粉样蛋白-β 沉积)和神经影像学数据(灰质体积、海马体积、白质高信号)的差异。使用 Cox 比例风险模型评估生物标志物与虚弱发生之间的关联。

结果

共有 195 名参与者(14.0%)在 5 年内出现虚弱。尽管 25-羟维生素 D 缺乏、同型半胱氨酸水平、低度炎症(持续增加的 C 反应蛋白 3-10mg/L)、灰质和海马体积在未调整模型中与虚弱发生显著相关,但这些关联在调整年龄、性别和其他混杂因素后消失。ω-3 指数是唯一与虚弱发生呈趋势相关的标志物(危险比:0.92;95%置信区间:0.83-1.01;p=0.082)。

结论

本研究未能确定能够预测社区居住的老年人 5 年内虚弱发生的生物标志物。需要进一步进行具有多个生物标志物和虚弱测量的纵向研究,以评估生物标志物水平变化与虚弱演变之间的长期关系。

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