流行病学研究已经确定了癌症和痴呆之间存在逆相关关系。虽然已经提出了潜在的方法学偏差，但目前没有研究系统地调查了单一数据集中每一种偏差来源的潜在可能性。我们使用了英国生物银行（UK Biobank）来比较使用不同分析规范在顺序上解决多种偏差来源，包括死亡的竞争风险、选择性存活、混杂偏差和诊断偏差时，癌症与痴呆关系的估计值。本研究纳入了140,959名年龄≥55岁的英国生物银行参与者，进行了入组前无痴呆症状的筛查，并链接了初级保健数据。我们使用癌症登记数据来识别英国生物银行入组前患有的已知癌症病例和入组后发生的新发癌症。我们使用Cox模型评估了已知癌症和新发癌症与全因痴呆、阿尔茨海默病（AD）和血管性痴呆的关联。我们使用时间变动模型评估诊断偏差。在中位随访时间为12.3年的过程中，诊断出3310例痴呆病例。全部新发癌症与全因痴呆的发病率呈正相关（风险比[HR] = 1.14，95% CI：1.02-1.29），但已知癌症与全因痴呆的关联则不显著（HR = 1.04，95% CI：0.92-1.17）。血管性痴呆的结果与此类似。AD与已知癌症或新发癌症均不相关。癌症诊断后的第一年，痴呆症的诊断显著增加（HR = 1.83，95% CI：1.42-2.36），之后这种关联减弱至无意义，这表明存在诊断偏差。癌症诊断后，健康服务利用或诊断或治疗的认知后果可能增加接受痴呆症诊断的机会，在基于电子健康记录的研究中可能存在潜在的诊断偏差。© 2023 Springer Nature B.V.

Epidemiological studies have identified an inverse association between cancer and dementia. Underlying methodological biases have been postulated, yet no studies have systematically investigated the potential for each source of bias within a single dataset. We used the UK Biobank to compare estimates for the cancer-dementia association using different analytical specifications designed to sequentially address multiple sources of bias, including competing risk of death, selective survival, confounding bias, and diagnostic bias. We included 140,959 UK Biobank participants aged ≥ 55 without dementia before enrollment and with linked primary care data. We used cancer registry data to identify cancer cases prevalent before UK Biobank enrollment and incident cancer diagnosed after enrollment. We used Cox models to evaluate associations of prevalent and incident cancer with all-cause dementia, Alzheimer's disease (AD), and vascular dementia. We used time-varying models to evaluate diagnostic bias. Over a median follow-up of 12.3 years, 3,310 dementia cases were diagnosed. All-site incident cancer was positively associated with all-cause dementia incidence (hazard ratio [HR] = 1.14, 95% CI: 1.02-1.29), but prevalent cancer was not (HR = 1.04, 95% CI: 0.92-1.17). Results were similar for vascular dementia. AD was not associated with prevalent or incident cancer. Dementia diagnosis was substantially elevated in the first year after cancer diagnosis (HR = 1.83, 95% CI: 1.42-2.36), after which the association attenuated to null, suggesting diagnostic bias. Following a cancer diagnosis, health care utilization or cognitive consequences of diagnosis or treatment may increase chance of receiving a dementia diagnosis, creating potential diagnostic bias in electronic health records-based studies.© 2023. Springer Nature B.V.