The competing risk of death and selective survival cannot fully explain the inverse cancer-dementia association

Abstract

Introduction: We evaluated whether competing risk of death or selective survival could explain the reported inverse association between cancer history and dementia incidence (incidence rate ratio [IRR] ≈ 0.62-0.85). Methods: A multistate simulation model of a cancer- and dementia-free cohort of 65-year-olds was parameterized with real-world data (cancer and dementia incidence, mortality), assuming no effect of cancer on dementia (true IRR = 1.00). To introduce competing risk of death, cancer history increased mortality. To introduce selective survival, we included a factor (prevalence ranging from 10% to 50%) that reduced cancer mortality and dementia incidence (IRRs ranged from 0.30 to 0.90). We calculated IRRs for cancer history on dementia incidence in the simulated cohorts. Results: Competing risk of death yielded unbiased cancer-dementia IRRs. With selective survival, bias was small (IRRs = 0.89 to 0.99), even under extreme scenarios. Discussion: The bias induced by selective survival in simulations was too small to explain the observed inverse cancer-dementia link, suggesting other mechanisms drive this association.