The comorbidity of depression and cognitive impairment is increasingly prevalent in clinical practice, particularly among the elderly population, which faces a higher risk of onset. Given the severity of the current comorbidity situation and the guiding significance of the traditional Chinese medicine (TCM) theory of “treating different diseases with the same method,” it is essential to systematically explore the underlying mechanisms of this comorbidity and conduct an in-depth analysis of TCM’s multi-target intervention strategies. According to TCM theory, the core pathogenesis of this comorbidity involves visceral deficiency, insufficiency of qi and blood, and phlegm turbidity clouding the orifices and disturbing the spirit, collectively leading to impaired mental functioning. Modern medical research, on the other hand, indicates that the pathological basis of this comorbidity arises from the interplay of multiple systemic mechanisms, including vascular pathologies, reduced brain-derived neurotrophic factor, hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, neuroinflammation, and gut microbiota dysbiosis. TCM demonstrates unique advantages in holistic intervention by multi-target regulation of neurotransmitters, suppression of neuroinflammation, enhancement of neuroplasticity, and modulation of the gut-brain axis. Through a systematic review of the mechanisms underlying the comorbidity of depression and cognitive impairment and the progress in multi-target intervention research in TCM, this study aims to provide new insights and references for scientific research and clinical practice in this field.

depression  /  cognitive impairment  /  comorbidity mechanism  /  traditional Chinese medicine  /  same treatment for different diseases