The role of dementia diagnostic delay in the inverse cancer-dementia association

Background Cancer is inversely associated with dementia. Using simulations, we examined whether this inverse association may be explained by dementia diagnosis timing, including death before dementia diagnosis and differential diagnosis patterns by cancer history. Methods We used multistate Markov simulation models to generate cohorts 65 years of age and free of cancer and dementia at baseline; follow-up for incident cancer (all cancers, breast, prostate, and lung cancer), dementia, dementia diagnosis among those with dementia, and death occurred monthly over 30 years. Models specified no true effect of cancer on dementia, and used age-specific transition rates calibrated to US population and cohort data. We varied the average lapse between dementia onset and diagnosis, including non-differential and differential delays by cancer history, and examined observed incidence rate ratios (IRRs) for the effect of cancer on dementia diagnosis. Results Non-differential dementia diagnosis delay introduced minimal bias (IRRs=0.98-1.02) for all cancer, breast, and prostate models and substantial bias (IRR=0.78) in lung cancer models. For the differential dementia diagnosis delay model of all cancer types combined, simulation scenarios with ≥20% lower dementia diagnosis rate (additional 4.5-month delay) in those with cancer history versus without yielded results consistent with literature estimates. Longer dementia diagnosis delays in those with cancer and higher mortality in those with cancer and dementia yielded more bias. Conclusions Delays in dementia diagnosis may play a role in the inverse cancer-dementia relationship, especially for more fatal cancers, but moderate differential delays in those with cancer were needed to fully explain the literature-reported IRRs.