Association of cardiovascular disease (CVD) or depression and memory has been studied. But hardly any studies on the association of coexistence of CVD and depression and memory.This is a prospective cohort study of a nationally representative sample of 12,272 adults aged 45 years and more who participated in the China health and retirement longitudinal study 2011 to 2015. All Variables were acquired by self-reporting questions. The associations between coexistence of CVD and depression with memory related disease (MRD) were investigated by using Cox proportional hazards regression models.Among the 12,272 participants (mean age 65.69 years; 46.8% male) in this study, 56.9% no CVD or depression and 6.7% coexistence of CVD and depression. After adjustment for age, sex, marriage, living place, registered permanent residence, education level, smoking status, alcoholic intake, sleep status, nap status, social communication, health before 15 years, life satisfaction, cognitive function, and 11 chronic diseases risk factors, depression alone was significantly high risk for MRD (HR:1.64; 95% CI: 1.09-2.49); coexistence of CVD and depression increased the risk for MRD significantly higher (HR: 4.72; 95%CI: 2.91-7.64).Diseases were all self-reported and we couldn't adjust for all the potential confounders, which might be prone to information error and residual confounding.In a nationally representative cohort with median 4 years of follow-up, depression alone and coexistence of depression and CVD could significantly increase the risk of MRD. Our study supports the idea of prevention of memory disease from a psycho-cardiology aspect.