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Importance: Neuropsychiatric symptoms, depressive symptoms in particular, are common in dementia patients but whether depressive symptoms in adulthood increases risk for dementia remains the subject of debate. Objective: To characterize the trajectory of depressive symptoms over 28 years prior to dementia diagnosis in order to determine whether depressive symptoms carry risk for dementia. Design: Whitehall II cohort study, study recruitment in 1985 and end of follow-up 2015. Setting General community, United Kingdom. Participants Up to 10,189 persons (33% women), aged 35-55 years in 1985. Exposures Depressive symptoms, assessed on 9 occasions between 1985 and 2012 using the General Health Questionnaire (GHQ-30). Main Outcome(s) and Measure(s) Incidence of dementia (N=322), between 1985 and 2015. Results: Those reporting depressive symptoms in 1985 (mean follow-up 27 years) did not have significantly increased risk of dementia (Hazard Ratio (HR)=1.21; 95% CI: 0.95, 1.54) in Cox regression adjusted for sociodemographic covariates, health behaviors, and chronic conditions. However, those with depressive symptoms in 2003 (mean follow-up 11 years) had an increased risk (HR=1.72; 95% CI: 1.21, 2.44). Those with chronic/recurring depressive symptoms (≥2 of 3 occasions) in the early study phase (mean follow-up 22 years) did not have excess risk (HR=1.02; 95% CI: 0.72, 1.44) but those with chronic/recurring symptoms in the late phase (mean follow-up 11 years) did have higher risk of dementia (HR=1.67; 95% CI: 1.11, 2.49). Analysis of retrospective depressive trajectories over 28 years, using mixed models and a backward time scale, shows that in those with dementia, differences in depressive symptoms compared to those without dementia became apparent 11 years (difference 0.61, p=0.02) before dementia diagnosis and became over nine times larger at the year of diagnosis (difference 5.81, p<0.001). Conclusions: Depressive symptoms in the early phase of the study corresponding to midlife, even when chronic/recurring, do not increase risk of dementia. Along with our analysis of depressive trajectories over 28 years, these results suggest that depressive symptoms are a prodromal feature of dementia or that the two share common causes. The findings do not support the hypothesis that depressive symptoms increase risk of dementia.

Original publication




Journal article


Jama psychiatry


American Medical Association (AMA)

Publication Date