Longitudinal Pathogenesis Reconstruction and Staged Treatment of Mild Cognitive Impairment Characterized Based on the Holistic Concept of Five Zang-Organss

Abstract

Mild Cognitive Impairment (MCI) represents an intermediate clinical state between physiological aging and dementia, serving as a critical intervention window to block the progression of cognitive decline toward dementia. Most existing studies treat the pathogenesis of “essence depletion and marrow reduction combined with phlegm-stasis intermingling” as a static cross-sectional consensus, which fails to capture the stage-specific pathogenetic features of MCI. Furthermore, clinical therapeutic strategies are often limited to isolated kidney-tonifying or phlegm-stasis resolving approaches, lacking systematic coordination guided by the holistic concept of five zang-organs. Based on a systematic review of contemporary traditional Chinese medicine (TCM) theories for differentiating and treating MCI and dementia, this study incorporates a temporal dimension and the holistic five zang-organ framework. Using multi-center clinical survey data, binary logistic regression was performed to verify the independent effects of “essence depletion and marrow reduction combined with phlegm-stasis intermingling” during the MCI stage and quantify their contribution magnitudes. A longitudinal pathogenesis model covering the full spectrum of cognitive impairment and a corresponding staged syndrome differentiation-treatment system were subsequently constructed. After adjusting for confounders including age and years of education, multivariate analyses identified phlegm turbidity syndrome (odds ratio [OR]=2.56, P<0.001) and marrow reduction syndrome (OR=2.52, P<0.001) as independent risk factors for MCI onset; these associations remained statistically significant in high-risk subgroups complicated with cerebrovascular disease and hypertension. These findings demonstrate that the core pathogenesis of MCI is characterized by predominant root deficiency (marrow reduction) accompanied by latent branch excess (phlegm turbidity). A staged diagnosis-treatment framework centered on the Kidney–Essence–Marrow–Brain axis with synergistic regulation of the heart, spleen, liver, and lung was established accordingly. A data-driven diagnostic criterion for the marrow depletion and phlegm obscuration syndrome was developed, alongside the therapeutic principle of “reinforcing the spleen to resolve phlegm, tonifying qi, and resuscitating orifices” exemplified by Xixin Decoction, bridging theoretical deductions and clinical empirical evidence.