BACKGROUND: Depression and dementia confer substantial global health burdens, particularly in women. Understanding the association between depression and dementia may inform new targets for prevention and/or early intervention.

OBJECTIVE: To investigate the association between depression in mid- and later-life and dementia (all-cause, Alzheimer's disease (AD) or vascular dementia (VaD)) in women.

METHODS: A prospective study design. Nurses were followed from age 60 years or entry into the cohort, whichever came last, until date of dementia, death, emigration, or end of follow-up, whichever came first. Cox regression models with age as the underlying timeline were used to estimate the associations between time-varying depression and incident dementia.

RESULTS: The study included 25,651 female Danish nurses (≥45 years) participating in the Danish Nurse Cohort. During an average of 23 years of follow-up, 1,232 (4.8%) nurses developed dementia and 8,086 (31.5%) were identified with at least two episodes of treated depression. In adjusted analyses, nurses with depression were at a statistically significant 5.23-fold higher risk of all-cause dementia (aHR 5.23:95% CI, 4.64-5.91) compared to those with no history of depression. The differential effects of depression were greater for VaD (aHR 7.96:95% CI, 5.26-12.0) than AD (aHR 4.64:95% CI, 3.97-5.42). Later life depression (>60 years) (aHR 5.85:95% CI, 5.17-6.64) and recurrent depression (aHR 3.51:95% CI, 2.67-4.61) elevated dementia risk. Severe depression tripled the risk of all cause dementia (aHR 3.14:95% CI, 2.62-3.76).

CONCLUSION: Both later life and severe depression substantially increase dementia risk in women, particularly VaD.