The influence of depression onset timing after gastrointestinal diseases on dementia risk.

INTRODUCTION: Gastrointestinal (GI) diseases have been implicated in neuropsychiatric conditions through gut-brain axis mechanisms involving inflammation and microbial dysbiosis. Depression is a common GI comorbidity and is associated with an increased risk of dementia. However, the impact of the timing of depression onset after GI disease on dementia remains unclear. METHODS: We conducted a retrospective cohort study of 106,245 older adults (≥60 years) using the Korean National Health Insurance Service-Elderly database from 2002 to 2020. Depression was classified as early onset (<2 years after GI diagnosis) or late onset (≥2 years). Dementia incidence was identified using International Classification of Diseases, 10th Revision codes and treatment records. Multivariable Cox models estimated the risk of dementia. RESULTS: Early-onset depression showed higher dementia incidence (22.38 vs 7.84 per 1000 person-years). The risk was highest within 6 months (hazard ratio [HR] 2.76) and declined with longer intervals. DISCUSSION: Depression shortly after GI disease predicts elevated dementia risk, underscoring the need for early psychiatric evaluation. HIGHLIGHTS: Dementia risk was highest when depression began within 6 months of GI disease diagnosis. Findings support gut-brain axis kinks in psychiatric and cognitive comorbidity. Dementia risk varied by timing of depression after GI disease diagnosis. Early treatment of depression in GI patients may lower future dementia risk.