Bocharova M, Borza T, Watne L O, Engedal K, O'Brien J T, Selbæk G, Idland A V, Hodsoll J, Young A H, Aarsland D
Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Research Centre for Age-Related Functional Decline and Disease, Innlandet Hospital Trust, Ottestad, Norway.
Mol Psychiatry. 2025 Feb 8. doi: 10.1038/s41380-025-02908-2.
Late-life depression (LLD) has been linked to increased likelihood of dementia, although mechanisms responsible for this association remain largely unknown. One feature frequently observed in both LLD and dementia is elevated levels of plasma inflammatory markers. The present study aimed to compare the levels of 12 plasma inflammatory markers between older people with LLD and controls, and to explore whether these markers, along with clinical characteristics, can predict dementia in patients with LLD within 3 years of follow-up. Using multiple linear regression with stepwise adjustment, we compared levels of plasma inflammatory markers (IL-1β, IL-1ra, IL-6, IL-10, IL-17a, IL-18, IL-33, TNFα, CD40L, IFN-γ, CCL-2 and CCL-4) between 136 inpatients with LLD (PRODE cohort) and 103 cognitively healthy non-depressed controls (COGNORM cohort). In the PRODE cohort, follow-up data was available for 139 patients (of them 123 had data on baseline plasma inflammatory markers); 36 (25.9%) developed dementia by Year 3 (n = 31 for those with cytokine data). Using Cox proportional hazards regression, we explored whether inflammatory markers and clinical characteristics of LLD (age of onset, treatment response, number of episodes) predicted progression to dementia during follow-up. Levels of IL-1ra, CCL-2, CCL-4, IFN-γ and IL-17a were significantly higher in LLD patients compared to controls in the majority of models. However, none of the inflammatory markers predicted progression from LLD to dementia in the PRODE cohort. Among clinical features, only poor response to treatment significantly predicted higher risk of progression to dementia.
晚年抑郁症（LLD）与痴呆症发病可能性增加有关，尽管造成这种关联的机制在很大程度上仍不清楚。在LLD和痴呆症中经常观察到的一个共同特征是血浆炎症标志物水平升高。本研究旨在比较LLD老年患者与对照组之间12种血浆炎症标志物的水平，并探讨这些标志物以及临床特征是否能够预测LLD患者在3年随访期内是否会发展为痴呆症。通过使用逐步调整的多元线性回归，我们比较了136例LLD住院患者（PRODE队列）和103例认知健康的非抑郁对照组（COGNORM队列）之间的血浆炎症标志物（IL-1β、IL-1ra、IL-6、IL-10、IL-17a、IL-18、IL-33、TNFα、CD40L、IFN-γ、CCL-2和CCL-4）水平。在PRODE队列中，有139例患者可获得随访数据（其中123例有基线血浆炎症标志物数据）；到第3年时，36例（25.9%）发展为痴呆症（有细胞因子数据的患者中为31例）。通过Cox比例风险回归，我们探讨了炎症标志物和LLD的临床特征（发病年龄、治疗反应、发作次数）是否能预测随访期间发展为痴呆症的情况。在大多数模型中，与对照组相比，LLD患者的IL-1ra、CCL-2、CCL-4、IFN-γ和IL-17a水平显著更高。然而，在PRODE队列中，没有一种炎症标志物能够预测从LLD发展为痴呆症的情况。在临床特征中，只有治疗反应不佳显著预测了发展为痴呆症的较高风险。
