Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Department of Human Anatomy, Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China.
Exp Gerontol. 2024 Nov;197:112603. doi: 10.1016/j.exger.2024.112603. Epub 2024 Oct 5.
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.
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.
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.
We provide evidence that frailty could increase depression risk independently of cognitive decline. Further research with a larger sample size is necessary.
衰弱、认知衰退和抑郁是老年人常见的综合征，且它们之间密切相关。然而，衰弱对抑郁的影响是否取决于认知衰退的作用仍不清楚。
我们基于全基因组关联研究（GWAS）数据库中的工具变量（IVs）进行了孟德尔随机化（MR）分析，并且还进行了一项包含 1362 名年龄≥65 岁的老年人的横断面研究进行验证。
多变量 MR 分析的结果表明，即使在控制认知表现的影响后，衰弱也显著增加了抑郁的风险。相反，在控制衰弱后，认知表现对抑郁风险的影响明显降低。在横断面研究中，衰弱介导了认知与抑郁之间关系的 24.04%，而认知则介导了衰弱与抑郁之间关系的 7.63%。
我们提供的证据表明，衰弱可能独立于认知衰退增加抑郁风险。需要进一步进行具有更大样本量的研究。
