529. **Rafaelsen Award Presentation** Cognitive function and the risk of later onset of depression in healthy individuals: a 10-year longitudinal study
Abstract Background Cognitive impairments are common in individuals with depression, but their role in the etiology of the disorder remains unclear. Aims & Objectives In this 10-year longitudinal study, we tested whether cognitive function is associated with a risk for developing future first-episode depression in individuals without prior psychiatric diagnoses. Method Individuals without prior neurological or psychiatric illnesses (n=372) completed the Symbol digit Modalities Test (SDMT) and the Letter-Number Sequencing (LNS) test, which assess processing speed and working memory, respectively. Cognitive data were linked to future depression diagnoses and antidepressant redemption records from the Danish National Registers. Cox regression analyses examined the relation between neurocognitive function and future depression risk over 5 years and 10 years, while controlling for age, sex, personality risk factors, familial risk of depression, and calendar year of cognitive assessment. Results The number of individuals who developed depression or had antidepressants prescribed for depression were 8 (5 women) and 13 (8 women) within 5 and 10 years, respectively. Lower SDMT score was associated with an elevated risk for depression (5 years: HR=1.14 CI [1.02-1.25], p=0.018; 10 years: HR=1.06, CI [1.00-1.14], p=0.042), while lower LNS score was not (5 years: HR=0.81, CI [0.57-1.50], p=0.24; 10 years: HR=0.99, CI [0.76-1.28], p=0.91). Conversion of SDMT scores to z-scores using normative data for evaluating potential clinical significance, revealed that individuals with z=-2 were at the greatest risk of developing depression. Discussion & Conclusions This study provides evidence that lower SDMT scores, a clinically used cognitive test that primarily assesses processing speed but also involves attention, recognition, and working memory, and which may be indicative of general cognitive capacity, are a risk factor for the onset of depression later in life. The findings raise the question if pro-cognitive interventions could be valuable for reducing the burden of depression in the general population.