Abstract
BACKGROUND: Although depressive symptoms are suspected to influence cognitive health, prospective evidence linking depressive symptoms to mild cognitive impairment (MCI) is scarce within large-scale Chinese cohorts. This study sought to analyze the graded association between initial depressive symptom severity and subsequent MCI risk in middle-aged and older adults in China, as well as to assess whether this relationship was moderated by other underlying factors. METHODS: Using data from the China Health and Retirement Longitudinal Study (CHARLS, 2011-2020), we included 9,461 participants aged ≥45 without baseline MCI. Depressive symptoms were assessed using the CESD-10 scale and categorized as none (<10), mild-moderate (10-20), or severe (≥21). Incident MCI was identified based on standardized criteria. Data analysis was performed using Cox proportional hazards regression models, which incorporated restricted cubic splines to flexibly model potential non-linear relationships. This primary analysis was further supplemented by comprehensive subgroup and sensitivity analyses to assess the heterogeneity of treatment effects and the robustness of the findings. RESULTS: During the nine-year follow-up period, a total of 1,276 new cases of MCI were documented. Analysis by depressive symptom severity revealed a graded increase in MCI risk relative to the asymptomatic reference group. In the fully adjusted model, participants with mild-to-moderate depressive symptoms exhibited a significantly increased risk of MCI (HR=1.363, 95%CI: 1.205-1.542, p<0.05), while a more pronounced risk elevation was observed in those with severe symptoms (HR=1.468, 95%CI: 1.123-1.918, p<0.05). Furthermore, each 1-SD (5.83 points) increase in CES-D score was associated with a 2.90% higher risk of MCI (HR=1.029, 95% CI: 1.020-1.039, p<0.001). Restricted cubic splines confirmed a significant linear dose-response relationship (p for nonlinear=0.419). Education significantly moderated the association, with a protective effect observed in individuals with higher education. The findings remained consistent when assessed through various sensitivity analyses. CONCLUSION: Baseline depressive symptoms are independently and dose-dependently associated with higher MCI risk in Chinese adults aged 45 and above. Education serves as a significant moderator. Integrating depression screening into MCI prevention strategies is recommended, particularly in less-educated populations.