Trajectories of depressive symptoms before diagnosis of dementia: a 28-year follow-up study
Singh-Manoux A., Dugravot A., Fournier A., Abell J., Ebmeier KP., Kivimaki M., Sabia S.
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.