Abstract
BACKGROUND: Loneliness is often accompanied by depression and is associated with an increased risk of dementia. However, evidence remains limited regarding how loneliness and depression jointly relate to future dementia risk, and whether depression may help explain the observed association between loneliness and dementia. METHOD: We conducted a study using prospective cohort data from three multinational populations. The association between loneliness, depression, and dementia risk was evaluated using Cox proportional hazards models. Mediation analysis was conducted to evaluate the potential contribution of depression to the observed association between loneliness and dementia risk. Additionally, both multiplicative and additive interaction methods were employed to assess the interaction between loneliness and depression with dementia risk, quantifying their combined associations. RESULTS: At baseline, a total of 133,388 participants were included in the study. Our study revealed a significant independent association between loneliness or depression and increased dementia risk. Additionally, compared to the group without loneliness or depressive symptoms, the other three groups had significantly higher risks of dementia during follow-up (loneliness only: HR = 1.26, 95% CI: 1.15-1.38; depression only: HR = 1.58, 95% CI: 1.41-1.78; loneliness with depression: HR = 1.98, 95% CI: 1.81-2.17). Mediation analysis showed that depression accounted for 36% of the loneliness-dementia association. Furthermore, we observed a significant additive interaction between loneliness and depression on dementia risk. CONCLUSIONS: This study examined the combined association of loneliness and depression with the risk of developing dementia, underscoring the importance of addressing loneliness and depression as potentially related factors in dementia prevention.