Dementia mediates the association of life‐course depression with mortality: A nationwide twin study

Abstract

AbstractBackgroundAlthough the association between depression and mortality has been investigated, the impact of depression in different periods of life on mortality remains inconclusive. We aimed to examine the association of depression with all‐cause mortality from a life‐course perspective, and to explore the roles of dementia, as well as genetic and early‐life environmental factors shared by twins, in this association.MethodFrom the Swedish Twin Registry, 44,919 twin individuals were followed for up to 18 years. Depression and dementia were ascertained using the Swedish National Patient Registry. Early‐life (<45 years), midlife (45‐64 years), and late‐life (≥ 65 years) depression were categorized according to the age of the first depression diagnosis. Deaths were identified through the Cause of Death Register. Generalized estimating equation model was used for unmatched analysis among all individuals. The mediating effect of dementia on the depression‐mortality association was estimated using generalized structural equation modeling. Conditional logistic regression model was used for co‐twin matched analysis among death‐discordant twin pairs.ResultAmong all the participants (mean age 59.34 years), 1,179 had a history of depression at baseline and 12,761 died during the follow‐up. In the unmatched analysis, the multivariate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of all‐cause mortality were 1.71 (1.46–2.00) for depression at any age, 1.72 (1.36–2.17) for early‐life, 1.51 (1.19–1.90) for midlife, and 4.10 (2.02‐8.34) for late‐life depression. Mortality was significantly higher in individuals with late‐life depression than those with earlier‐life depression (P<0.05). Depression at any age was also associated with an increased risk of mortality with dementia (OR 1.62, 95% CI 1.28–2.05). In the mediation analysis, 56.74% of the depression‐mortality association was mediated by dementia. In the co‐twin matched analysis, the OR (95% CI) for the depression‐mortality association was 1.70 (1.22–2.38). No statistically significant difference in ORs between the unmatched and co‐twin matched analyses was observed (P = 0.09).ConclusionDepression, especially occurring in late life, is associated with an increased all‐cause mortality. Dementia in late life mediates over 50% of the depression‐mortality association, but genetic and early‐life environmental factors appear not to account for this association.