Abstract Background Depressive symptoms are closely associated with cognitive decline and risk of incident dementia, and plasma biomarkers may play a significant role in this relationship. We aimed to investigate the influence of plasma biomarkers and explore the underlying mechanisms. Methods This study included 1,658 dementia-free community residents recruited in 2009–2011 from the Shanghai Aging Study. At baseline, we assayed plasma phosphorylated tau 217 (p-tau217) and neurofilament light chain (NfL), and assessed depressive symptoms using the Center for Epidemiologic Studies Depression scale. Cox regression models were performed to estimate the risks of incident dementia and Alzheimer’s disease (AD) during the 5-year follow-up. Parallel and serial mediation models were applied to investigate whether plasma p-tau217 and NfL mediated the relationship between depressive symptoms and cognitive decline. Results Older adults with depressive symptoms had higher risks of dementia and AD, especially among those with higher concentrations of baseline plasma p-tau217/NfL. Sex-specific analysis revealed that depressive symptoms combined with high plasma NfL increased AD risk in men (hazard ratio, HR 95% confidence interval, CI = 5.89 2.01, 17.27, p = 0.001), whereas women with depressive symptoms and high plasma p-tau217 showed higher AD risk (HR 95%CI = 6.07 2.82, 13.09, p < 0.001). Parallel mediation analysis revealed that plasma p-tau217/NfL mediated the relationship between depressive symptoms and cognitive decline, respectively. Additionally, serial mediation analysis found p-tau217 precedes NfL within the mediating pathway ( β = 0.403, bootstrap 95% CI: 0.347, 0.452). Conclusions Plasma p-tau217 and NfL could individually or jointly mediate the relationship between depressive symptoms and cognitive decline.
Xia et al. (Thu,) studied this question.