Frailty increases depression risk independently of cognitive decline: Insights from Mendelian randomization and cross-sectional analysis

IF 3.9

Experimental gerontology Pub Date : 2024-10-05 DOI:10.1016/j.exger.2024.112603

Wenjie Li , Qi Tian , Jingxi Duan , Xintong Liu , Jianwei Shou , Ting Tang , Weihua Yu , Yang Lü

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Abstract

Background

Frailty, cognitive decline, and depression are common syndromes among the elderly and are closely interconnected. However, it is still unclear whether the impact of frailty on depression depends on the role of cognitive decline.

Method

We conducted the Mendelian randomization (MR) analysis based on the instrumental variables (IVs) from the genome-wide association study (GWAS) databases, and we also performed a cross-sectional study consisting of 1362 older adults aged ≥65 for validation.

Results

The results of the multivariable MR analysis showed that frailty significantly increased the risk of depression, even after controlling for the influence of cognitive performance. Conversely, after controlling for frailty, the effect of cognitive performance on depression risk was noticeably reduced. In the cross-sectional study, frailty mediated 24.04 % of the relationship between cognition and depression, and cognition mediated 7.63 % of the relationship between frailty and depression.

Conclusions

We provide evidence that frailty could increase depression risk independently of cognitive decline. Further research with a larger sample size is necessary.

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虚弱会增加抑郁风险，与认知能力下降无关：孟德尔随机化和横断面分析的启示。

背景：虚弱、认知能力下降和抑郁是老年人常见的综合征，它们之间存在密切联系。然而，虚弱对抑郁症的影响是否取决于认知能力下降的作用，目前仍不清楚：方法：我们根据全基因组关联研究（GWAS）数据库中的工具变量（IVs）进行了孟德尔随机化（MR）分析，并对 1362 名年龄≥65 岁的老年人进行了横断面研究以进行验证：结果：多变量 MR 分析结果显示，即使控制了认知能力的影响，虚弱也会显著增加抑郁的风险。相反，在控制了虚弱之后，认知能力对抑郁风险的影响明显降低。在横断面研究中，虚弱介导了 24.04% 的认知与抑郁之间的关系，而认知介导了 7.63% 的虚弱与抑郁之间的关系：我们提供的证据表明，虚弱会增加抑郁风险，而与认知能力下降无关。有必要进行样本量更大的进一步研究。

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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