Synergistic Effect of Depression and Cerebrovascular Disease in Mid- to Late-life on the Risk for Dementia: A Nationwide Population-based Cohort Study

Abstract

Background: Dementia is a progressive neurocognitive disease with a substantial social burden. No apparent breakthroughs in treatment options have evolved so far, suggesting that disease prevention for at-risk populations is essential. Depression and cerebrovascular disease (CVD) are known independent risk factors for dementia, but no studies have examined whether the risk for dementia among people with both illnesses is higher than the sum from each effect individually. This study aims to evaluate the dementia risk among people with depression, CVD, or both, compared to those with neither.Methods: A population-based cohort study analyzing the Korean National Health Insurance Service-National Sample Cohort database was conducted for all individuals aged over 50 years. This population had not been diagnosed with dementia at baseline, and was followed up from January 1, 2005, to December 31, 2013. The analyses used a time-varying Cox proportional hazard regression model that was adjusted for potential confounding factors. The synergistic effect of depression and CVD was estimated by calculating the attributable proportion (AP) due to interaction.Results: A total of 242,237 participants were included in the analytical sample, and 12,735 (5.3%) participants developed dementia. Compared with participants without depression or CVD, the adjusted hazard ratio for the incidence of dementia for those with depression alone was 2.35 (95% CI 2.21-2.49); CVD alone, 3.25 (95% CI 3.11-3.39); and comorbid depression and CVD, 5.02 (95% CI 4.66-5.42). The synergistic effect between depression and CVD was statistically significant (AP due to interaction = 0.08, P-value = 0.037), whereby 8% of incident dementia among those with comorbid depression and CVD was attributed to the concomitance of the two illnesses.Conclusions: In this population-based nationwide cohort with a long-term follow-up, depression and CVD were associated with an increased risk of dementia, and their coexistence had a synergistic association.