Van Dyk Kathleen, Siddarth Prabha, Rossetti Maura, Ercoli Linda M, Milillo Michaela M, Lavretsky Helen
Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles, CA, USA.
UCLA Immunogenetics Center, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Brain Behav Immun Health. 2020 Nov 7;9:100167. doi: 10.1016/j.bbih.2020.100167. eCollection 2020 Dec.
Geriatric depression is frequently accompanied by cognitive complaints and inflammation that increase risk for treatment-resistant depression and dementia. Memantine, a neuroprotective drug, can improve depression, inflammation, and help prevent cognitive decline. In our six-month clinical trial, escitalopram/memantine (ESC/MEM) improved mood and cognition compared to escitalopram/placebo treatment (ESC/PBO; NCT01902004). In this report, we examined the impact of baseline inflammation on mood and cognitive outcomes.
We measured a panel of inflammatory cytokine markers using Human 38-plex magnetic cytokine/chemokine kits (EMD Millipore, HCYTMAG-60K-PX38) in 90 older adults 60 years and older with major depression enrolled in a 6-month double-blind placebo-controlled trial of escitalopram + memantine (ESC/MEM) in depressed older adults with subjective memory complaints. Four cytokine factors were derived and linear models were estimated to examine the predictive ability of cytokine levels on treatment induced change in depression and cognition.
Of the 90 randomized participants, 62 completed the 6-month follow up assessment. Both groups improved significantly on depression severity (HAM-D score), but not on cognitive outcomes at six months. Cytokine factor scores were not significantly different between ESC/MEM (n = 45) and ESC/PBO (n = 45) at baseline. Pro-inflammatory biomarkers at baseline predicted a decline in executive functioning in the ESC/PBO group but not in the ESC/MEM group, interaction F(1,52) = 4.63, p = .04.
In this exploratory analysis, the addition of memantine to escitalopram provided a protective effect on executive functioning in older depressed adults. Future studies are needed to replicate the association of cytokine markers to antidepressant and neuroprotective treatment-related change in cognition in geriatric depression.
老年抑郁症常伴有认知障碍和炎症，这会增加难治性抑郁症和痴呆症的风险。美金刚是一种神经保护药物，可改善抑郁、炎症，并有助于预防认知衰退。在我们为期六个月的临床试验中，与艾司西酞普兰/安慰剂治疗（ESC/PBO；NCT01902004）相比，艾司西酞普兰/美金刚（ESC/MEM）改善了情绪和认知。在本报告中，我们研究了基线炎症对情绪和认知结果的影响。
我们使用人38种细胞因子/趋化因子磁珠试剂盒（EMD Millipore，HCYTMAG-60K-PX38），对90名60岁及以上患有重度抑郁症且有主观记忆障碍的老年人进行了一组炎症细胞因子标志物的检测。这些老年人参与了一项为期6个月的双盲安慰剂对照试验，该试验使用艾司西酞普兰 + 美金刚（ESC/MEM）治疗老年抑郁症患者。我们得出了四个细胞因子因子，并估计了线性模型，以检验细胞因子水平对治疗引起的抑郁和认知变化的预测能力。
在90名随机参与者中，62人完成了6个月的随访评估。两组在抑郁严重程度（汉密尔顿抑郁量表评分）上均有显著改善，但在六个月时认知结果无改善。在基线时，ESC/MEM组（n = 45）和ESC/PBO组（n = 45）的细胞因子因子得分无显著差异。基线时的促炎生物标志物预测了ESC/PBO组执行功能的下降，但在ESC/MEM组中未出现，交互作用F(1,52) = 4.63，p = 0.04。
在这项探索性分析中，在艾司西酞普兰中添加美金刚对老年抑郁症患者的执行功能具有保护作用。未来需要开展研究，以重复细胞因子标志物与老年抑郁症中抗抑郁和神经保护治疗相关认知变化之间的关联。
