Depressive symptom profiles predict dementia onset and brain pathology in older persons. The AGES-Reykjavik study

Late-life depression (LLD) increases risk for dementia and brain pathology, but possibly this is only true for one or more symptom profiles of LLD. In 4354 participants (76 ± 5 years; 58% female) from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, we identified five LLD symptom profiles, based on the Geriatric Depression Scale-15 (no LLD (57%); apathy (31%); apathy with emptiness (2%), mild LLD (8%) and severe LLD (2%)). Cox regression analyses showed that severe LLD, mild LLD and apathy increased risk of dementia up to 12 years, compared to no LLD. Additionally, hippocampal volume loss and white matter lesion increase, were assessed on 1.5 T MR images, at baseline and after 5 years follow-up. Only severe LLD showed increased WML volume over time, but not on hippocampal volume loss. WML increase over time mediated partially the relation between mild LLD and dementia but not for the other symptom profiles. It appears that hippocampal atrophy and LLD are independent predictors for dementia incidence, whereas for mild LLD the risk for dementia is partially mediated by WML changes.