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IMPORTANCE: Neuropsychiatric 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. OBJECTIVE: To 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 PARTICIPANTS: Up 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. EXPOSURES: Depressive symptoms assessed on 9 occasions between 1985 and 2012 using the General Health Questionnaire. MAIN OUTCOMES AND MEASURES: Incidence of dementia (n = 322) between 1985 and 2015. RESULTS: Of 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 

Original publication




Journal article


JAMA Psychiatry

Publication Date





712 - 718


Adult, Aged, Aged, 80 and over, Comorbidity, Dementia, Depression, Follow-Up Studies, Humans, Incidence, Middle Aged, Prodromal Symptoms, Risk, United Kingdom