Is Cancer Protective for Subsequent Alzheimer’s Disease Risk? Evidence From the Utah Population Database

Abstract

Objective: Several studies have suggested that cancer is associated with a reduced risk of the development of Alzheimer's disease (AD). This study seeks to improve our understanding of the association between cancer and the development of AD by showing how mortality selection alters this relationship. Method: A retrospective cohort study was carried out examining 92,425 individuals (47,873 women and 44,552 men) from the Utah Population Database with and without a history of any primary cancer identified by the Utah Cancer Registry. All individuals were aged 65-79 years and free of dementia in 1992 and followed for upwards of 18 years (1992-2009) for AD ascertainment, which was identified using diagnostic information from Medicare claims data. Results: We replicate previous results suggesting that cancer is associated with reduced risk of subsequent AD under specific statistical model specifications. However, these results should not be interpreted as evidence of an etiological association. We conclude that higher rates of overall mortality among individuals with cancer relative to those without cancer induce the widely reported putative protective association with cancer. Conclusion: Careful consideration of model specification and the profound effects of mortality selection in the older adult population is essential when investigating the relationship between aging-related diseases such as cancer and AD. We show that cancer does not provide protection from AD as previously described in the literature. Social scientists seeking to understand social disparities in disease outcomes among older adults may therefore want to strongly consider the role of mortality selection which, if uncorrected, may generate biased associations.

[P1–566]: Is There an Association Between Cancer and Dementia in Cohorts With and Without T2dm? A National Observational Study

“…No evidence of a protective effect of cancer vis a vis overall LOD and dementia attributable to AD (AD-LOD) in both non-T2DM and T2DM cohorts was noted. This finding is in line with reports from recent population-based studies, who similarly observed nil significant associations (Hanson HA et al, 2016, Schmidt SA et al, 2017, Freedman DM et al, 2016. Upon examining the cause-specific and sub distribution hazard models, my findings suggest that the inverse association observed between cancer, lung cancer and LOD, especially in the T2DM cohort, is most likely due to mortality selection.…”

“…Finally, a retrospective study, using the UTAH population database, examined several different statistical techniques to explore the association between cancer and AD-LOD in 94,435 individuals (Hanson HA et al, 2016). The authors found that different model specifications can change the direction of the results majorly.…”

“…However, when cancer was specified as a time varying covariate, no inverse association between cancer and AD-LOD was found. Additionally the authors used several statistical methodologies to account for death as a competing risk, and described mortality selection as the main reason behind the inverse association observed (Hanson HA et al, 2016). Tables 2 and 3.…”

Association of cancer and Alzheimer's disease risk in a national cohort of veterans

“…One group recently showed that accounting for competing risks eradicates the inverse association between cancer and AD. 17 However, the decision about whether to account for competing risks depends on the question the analysis is trying to answer. 18 When the goal is to measure the association between two diseases for the purpose of determining a causal relationship, then it is appropriate to ignore the competing risk, as is routinely done when using Cox models in an elderly cohort.…”

Evidence of a Causal Association Between Cancer and Alzheimer’s Disease: a Mendelian Randomization Analysis

“…The reduced risk of AD in those diagnosed with cancer may be due to higher mortality rates among cancer patients and survivors, especially for cancers with poor survival rates, such as pancreatic cancer. 10 Many studies are limited by small sample sizes 7 11 12 , short follow-up periods 7 9 12 13 , or gender bias. 9 Other issues include appropriate diagnoses and changing guidelines, the potential negative effects of chemotherapy on cognition, and behavioral and sociodemographic variables related to both AD and cancer.…”