Sex-Specific Associations Between Depressive Symptoms and Risk for Subsequent Dementia

Background: An association between depression and an increased risk for subsequent dementia is well-established. Sex-specific associations are understudied yet. Objective: We aimed to investigate sex-specific associations between depressive symptoms and dementia risk. Methods: Longitudinal analyses were conducted in a pooled data set (n = 4,255, mean age = 80 years) of two prospective cohort studies (LEILA 75+, AgeCoDe). Depressive symptoms were harmonized by dichotomized scores of two different depression screening scales using established cutoffs. Transition to dementia was used as outcome in Cox proportional hazards models. Results: Depressive symptoms at baseline were associated with an increased risk for subsequent dementia, and this association was more pronounced in males (interaction of depressive symptoms x sex: HR = 1.64, 95% CI: 1.02-2.64, p = 0.042) in a model adjusted for study, age, and education. After additional adjustment for subjective and objective cognition, depressive symptoms and their interaction with sex (HR = 1.38, 95% CI: 0.85-2.23, p = 0.188) were no longer significantly associated with the risk for subsequent dementia. Sex-stratified analyses showed stronger and significant associations between depressive symptoms and subsequent dementia in men (e.g., HR = 2.10, 95% CI: 1.36-3.23, p = 0.001, compared to HR = 1.28, 95% CI: 1.04-1.58, p = 0.020, in women). Conclusion: Overall, we provide evidence for a stronger association between depression and dementia in men compared to women. Depressive symptoms should be diagnosed, monitored, and treated, not only due to depression, but also with respect to the risk for subsequent dementia, especially in elderly men.