Abstract

This study aims to investigate the association and dose-response relationship between depression, dementia, and all-cause mortality based on a national cohort study of elderly people in Japan. We conducted a longitudinal study of 44,546 participants aged ≥65 from 2010-2019 Japanese Gerontological Evaluation Study (JAGES). The Geriatric Depression Scale (GDS-15) was used to assess depressive symptoms and the long-term care insurance (LTCI) was used to assess dementia. Fine-gray models and Cox proportional hazard models were used to explore the effect of depression severity on the incidence of dementia and all-cause mortality, respectively. Causal mediation analysis (CMA) to explore the extent of association between dementia-mediated depression and all-cause mortality. We found that both minor and major depressive symptoms were associated with the increased cumulative incidence of dementia and all-cause mortality, especially major depressive symptoms (P < 0.001). The multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for dementia were 1.25 (1.19-1.32) for minor depressive symptoms and 1.42 (1.30-1.54) for major depressive symptoms in comparison to non-depression; P for trend < 0.001. The multivariable-adjusted HRs and 95% CIs for all-cause mortality were 1.27 (1.21-1.33) for minor depressive symptoms and 1.51 (1.41-1.62) for major depressive symptoms in comparison to non-depression; P for trend < 0.001. Depression has a stronger impact on dementia and all-cause mortality among the younger group. In addition, dementia significantly mediated the association between depression and all-cause mortality. Interventions targeting major depression may be an effective strategy for preventing dementia and premature death.

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