Interval from Cancer Diagnosis to Depression Onset and Risk of Dementia in Cancer Survivors
Menée en Corée à partir de données portant sur 385 092 patients atteints d'un cancer diagnostiqué entre 2009 et 2013 (durée médiane de suivi : 11,7 ans), cette étude de cohorte évalue l'association entre le délai de survenue d'une dépression après diagnostic du cancer et le risque de démence
Background: The primary aim of our study is to examine how the timing of depression after cancer diagnosis relates to the risk of all-cause dementia (ACD) and Alzheimer disease (AD) and to compare time-fixed and time-varying modeling approaches.
Methods: We conducted a nationwide cohort study using Korean National Health Insurance Service data on 385,092 individuals aged ≥55 years diagnosed with cancer between 2009 and 2013, with no dementia or depression, followed through 2023. Depression was identified using International Classification of Diseases, Tenth Revision, codes F32 to F33 and categorized by the interval from cancer diagnosis. Depression was modeled as a baseline time-fixed or a time-varying exposure. The primary outcome was ACD, and the secondary outcome was AD. Cox proportional hazards models estimated adjusted hazard ratios (aHR) and 95% confidence intervals (CI), adjusting for demographic, lifestyle, and cardiometabolic factors.
Results: Over a median follow-up of 11.7 years, 71,600 participants (18.6%) developed ACD. Time-fixed models suggested an increased dementia risk for depression diagnosed within 5 years after cancer but an apparent inverse association for depression diagnosed >5 years after cancer (aHR, 0.90; 95% CI, 0.87–0.93). In contrast, time-varying models showed consistently elevated risks across all depression-onset intervals, including >5 years after cancer (aHR, 2.09; 95% CI, 2.02–2.17). Results were similar for AD.
Conclusions: Depression at any time after cancer diagnosis is associated with increased dementia risk when modeled. Time-fixed analyses may introduce immortal time bias and mischaracterize risk, underscoring the importance of time-varying approaches in survivorship research.
Impact: Modeling postcancer depression as a time-varying exposure clarifies dementia risk estimates and informs survivorship mental health strategies.
Cancer Epidemiology, Biomarkers & Prevention , résumé, 2026