Evolution of depressive symptoms in the 15 years preceding dementia

Depression has been consistently linked to the onset of dementia, but the temporality and nature of this association-whether causal, prodromal or due to shared pathophysiology-remain unresolved. Longitudinal studies with extended follow-up are necessary to clarify these relationships. This study aimed to characterise the trajectory of depressive symptoms during the 15 years preceding a dementia diagnosis, with particular attention to variations by dementia aetiology.

This nested case-control study was conducted within the Three-City Study cohort, a prospective population-based study initiated in 1999. The cohort included 9294 community-dwelling individuals aged 65 and older, followed for 15 years in three French cities (Bordeaux, Dijon, Montpellier). Depressive symptoms were assessed using the Centre for Epidemiological Studies Depression scale in 1028 dementia cases and 1028 matched controls. Trajectories of depressive symptoms were analysed over the 15 years preceding the index date (dementia diagnosis).

No significant differences in depressive symptomatology (p=0.69) or the frequency of depressive states (OR 1.21, 95% CI 0.51 to 2.87) were observed between cases and controls 12-15 years before the index date. Gradual differences emerged over time, becoming significant 6-8 years prior to dementia onset (p<0.001) and peaking 2 years before the index date (OR 2.93, 95% CI 2.27 to 3.80). These differences were more pronounced in non-Alzheimer's dementia cases.

Depressive symptoms progressively increased in the years leading up to dementia diagnosis, with the most pronounced elevations occurring in non-Alzheimer's dementia.