• Archana Singh-Manoux, Aline Dugravot, Agnes Fournier, Jessica Abell, Klaus Ebmeier, Mika Kivimäki, and Séverine Sabia.
• INSERM U1018, Centre for Research in Epidemiology and Population Health, Paris, France2Department of Epidemiology and Public Health, University College London, London, England.
• JAMA Psychiatry. 2017 Jul 1; 74 (7): 712-718.

ImportanceNeuropsychiatric symptoms, depressive symptoms in particular, are common in patients with dementia but whether depressive symptoms in adulthood increases the risk for dementia remains the subject of debate.ObjectiveTo characterize the trajectory of depressive symptoms over 28 years prior to dementia diagnosis to determine whether depressive symptoms carry risk for dementia.Design, Setting, And ParticipantsUp to 10 308 persons, aged 35 to 55 years, were recruited to the Whitehall II cohort study in 1985, with the end of follow-up in 2015. Data analysis for this study in a UK general community was conducted from October to December 2016.ExposuresDepressive symptoms assessed on 9 occasions between 1985 and 2012 using the General Health Questionnaire.Main Outcomes And MeasuresIncidence of dementia (n = 322) between 1985 and 2015.ResultsOf the 10 189 persons included in the study, 6838 were men (67%) and 3351 were women (33%). Those reporting depressive symptoms in 1985 (mean follow-up, 27 years) did not have significantly increased risk for 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 for 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 with those without dementia became apparent 11 years (difference, 0.61; 95% CI, 0.09-1.13; P = .02) before dementia diagnosis and became more than 9 times larger at the year of diagnosis (difference, 5.81; 95% CI, 4.81-6.81; P < .001).Conclusions And RelevanceDepressive symptoms in the early phase of the study corresponding to midlife, even when chronic/recurring, do not increase the risk for 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 2 share common causes. The findings do not support the hypothesis that depressive symptoms increase the risk for dementia.

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