Association of life‐course depression with the risk of dementia in late life: A nationwide twin study

Background Depression in later life has been linked to dementia, yet whether depression is a prodromal phase or risk factor for dementia is still under debate. Thus, looking into the time window of depression occurrence may help unveil the nature of this link. We aimed to examine the association of depression with dementia from a life-course perspective, and to explore the roles of genetic and early-life environmental factors shared by twins, and education in this association. Method Within the Swedish Twin Registry, 41,727 dementia-free twin individuals (mean age 60 years) were observed for 18 years to detect incident dementia. Life-course depression was ascertained from the Patient Registry and divided as early-, mid-, late-, early- to mid-life, mid- to late-life, and lifelong depression according to the age of occurrence. Dementia was ascertained based on the same registry. Generalized estimating equation (GEE) model was used for unmatched case-control analysis and conditional logistic regression was used for co-twin matched case-control analysis. Result Of all participants, 2,832 (6.8%) had depression and 3,258 (7.8%) developed dementia. In the multi-adjusted GEE model of unmatched analysis, the odds ratio (OR) of dementia was 1.93 [95% confidence interval (CI): 1.69–2.21] for depression at any age. In stratified analyses, the ORs (95% CIs) of dementia were 0.98 (0.51–1.90) for early-life, 1.46 (1.09–1.95) for mid-life, 2.16 (1.82–2.56) for late-life, 1.62 (0.60–4.35) for early- to mid-life, 2.24 (1.49–3.36) for mid- to late-life, and 2.65 (1.17–5.98) for lifelong depression respectively. No statistically significant difference in ORs from the unmatched and co-twin matched analyses was observed (P = 0.60). In joint exposure analysis, the dementia risk associated with mid-life depression was attenuated by education ≥8 years. Conclusion Not only late-life depression, but also depression beginning from midlife is associated with dementia. Genetic and early-life environmental factors seem not to account for the association. Higher education might buffer the impact of mid-life depression on dementia.