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 U.S. population and cohort data. We varied the average lapse between dementia onset and diagnosis, including nondifferential and differential delays by cancer history, and examined observed incidence rate ratios (IRRs) for the effect of cancer on dementia diagnosis. Results Nondifferential 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.

中文翻译：

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痴呆诊断延迟在逆向癌症-痴呆关联中的作用

背景 癌症与痴呆呈负相关。使用模拟，我们检查了这种反向关联是否可以用痴呆诊断时间来解释，包括痴呆诊断前的死亡和癌症病史的鉴别诊断模式。方法 我们使用多状态马尔可夫模拟模型生成基线时 65 岁且无癌症和痴呆症的队列；对癌症（所有癌症、乳腺癌、前列腺癌和肺癌）、痴呆症、痴呆症患者的痴呆症诊断和死亡的随访在 30 年中每月发生一次。模型没有明确指出癌症对痴呆症有真正的影响，并使用了根据美国人口和队列数据校准的特定年龄转换率。我们改变了痴呆症发作和诊断之间的平均间隔时间，包括癌症病史的无差异和差异延迟，并检查了癌症对痴呆症诊断影响的观察到的发病率比 (IRR)。结果 非差异性痴呆诊断延迟对所有癌症、乳腺癌和前列腺模型引入了最小偏差 (IRRs = 0.98–1.02)，对肺癌模型引入了显着偏差 (IRR = 0.78)。对于所有癌症类型组合的差异性痴呆诊断延迟模型，与没有癌症病史的患者相比，痴呆诊断率降低 ≥ 20%（额外延迟 4.5 个月）的模拟情景产生的结果与文献估计一致。癌症患者的痴呆症诊断延迟时间越长，癌症和痴呆症患者的死亡率越高，这会产生更多的偏差。结论 痴呆症诊断延迟可能在癌症与痴呆症的反向关系中发挥作用，尤其是对于更致命的癌症，