Association Between Alzheimer Disease and Cancer With Evaluation of Study Biases

Abstract

Key Points Question Does an association exist between cancer and subsequent Alzheimer disease (AD), and how likely is it that such a finding is associated with methodological bias rather than with a true common etiology? Findings In this systematic review and meta-analysis of 22 cohort and case-control studies representing 9 630 435 individuals, cancer diagnosis was associated with 11% decreased incidence of AD. Bias-adjusted metaregressions suggested that competing risks and diagnostic bias were unlikely explanations for the observed association, whereas survival bias remains to be ruled out. Meaning The observed inverse association between cancer and AD does not seem to be a consequence of competing risks, known confounding, or diagnostic bias.

Investigating the association between cancer and the risk of dementia: Results from the Memento cohort

“…This observed protective effect of cancer against dementia is largely in line with previous research 1,4,10,22,23 . For example, a recent prospective cohort study found that individuals diagnosed with cancer during follow‐up had a 3‐fold reduction in risk of AD 4 .…”

“…Therefore, it was not possible to investigate potential differential effects on dementia risk according to cancer type. To this effect, previous research has found that the protective effect of cancer on dementia risk may be limited to certain types of cancer, notably head and neck cancers 2,23,35 . Finally, due to the limited amount of follow‐up time, it was not possible to investigate the duration of protective effect of cancer on dementia risk.…”

“…This observed protective effect of cancer against dementia is largely in line with previous research. 1 , 4 , 10 , 22 , 23 For example, a recent prospective cohort study found that individuals diagnosed with cancer during follow‐up had a 3‐fold reduction in risk of AD. 4 Recent meta‐analyses similarly reflect a protective effect in extant literature, estimating an overall pooled effect size associated with a 15% to 37% decrease in risk of AD.…”

Focus on the Complex Interconnection between Cancer, Narcolepsy and Other Neurodegenerative Diseases: A Possible Case of Orexin-Dependent Inverse Comorbidity

“…A recent systematic review and meta-analysis confirmed a weak but significant decrease in AD risk comparing older adults with vs. without a previous cancer diagnosis, but it could not rule out a role of survival bias [ 14 ]. Epidemiological studies indicate that AD patients have a lower risk of developing lung cancer and a higher risk of developing glioblastoma: transcriptomic meta-analyses reveal a significant number of genes with reverse expression patterns in AD and lung cancer, compared to AD and glioblastoma [ 15 ].…”

Choosing questions before methods in dementia research with competing events and causal goals

“…This may explain counterintuitive results, where exposures that are known to be harmful for mortality risk, such as smoking [4,5] or history of cancer [6], sometimes seem protective for the risk of dementia. Authors have attempted to make sense of these counterintuitive results by naming biases such as "competing risk bias" or "survival bias" [7,8]. However, the bias associated with a particular analytic method cannot be defined or assessed if the causal question is not explicitly specified.…”