The competing risk of death and selective survival cannot fully explain the inverse cancer-dementia association - PubMed (original) (raw)

. 2020 Dec;16(12):1696-1703.

doi: 10.1002/alz.12168. Epub 2020 Sep 3.

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The competing risk of death and selective survival cannot fully explain the inverse cancer-dementia association

Eleanor Hayes-Larson et al. Alzheimers Dement. 2020 Dec.

Abstract

Introduction: We evaluated whether competing risk of death or selective survival could explain the reported inverse association between cancer history and dementia incidence (incidence rate ratio [IRR] ≈ 0.62-0.85).

Methods: A multistate simulation model of a cancer- and dementia-free cohort of 65-year-olds was parameterized with real-world data (cancer and dementia incidence, mortality), assuming no effect of cancer on dementia (true IRR = 1.00). To introduce competing risk of death, cancer history increased mortality. To introduce selective survival, we included a factor (prevalence ranging from 10% to 50%) that reduced cancer mortality and dementia incidence (IRRs ranged from 0.30 to 0.90). We calculated IRRs for cancer history on dementia incidence in the simulated cohorts.

Results: Competing risk of death yielded unbiased cancer-dementia IRRs. With selective survival, bias was small (IRRs = 0.89 to 0.99), even under extreme scenarios.

Discussion: The bias induced by selective survival in simulations was too small to explain the observed inverse cancer-dementia link, suggesting other mechanisms drive this association.

Keywords: Alzheimer's disease; cancer; competing risks; dementia; selection bias; simulation.

© 2020 the Alzheimer's Association.

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Figures

FIGURE 1

FIGURE 1

Schematic of multistate simulation model. Arrow thicknesses qualitatively represent relative magnitude of incidence rates. Blue arrows, transition from no dementia to dementia. Orange arrows, transition from no history of cancer to history of cancer. Green arrows, transition to death. Transition rates were obtained from real-world data. For example, for the age band 65 to 70, the dementia incidence rate is 5.4/1000 person-years (PY) (ACT study), cancer (all types) incidence rate is 162.2/1,000PY (SEER data). The overall mortality rate is 413.3/1000 PY (U.S. life tables); cancer increases the mortality rate 2.92-fold (SEER), dementia increases the mortality rate 7.45-fold, and the effects of cancer and dementia on mortality are multiplicative. In the base case selective survival model, U reduces both cancer mortality and dementia incidence rates by 30%. Abbreviations: ACT = Adult Changes in Thought; SEER = Surveillance, Epidemiology, and End Results

FIGURE 2

FIGURE 2

Proportion of cohort in each state in the all-cancers model for the scenario with competing risk of death only

FIGURE 3

FIGURE 3

Observed incidence rate ratios (IRR) from simulation scenarios with (A) competing risk of death only, and (B) competing risk of death and selective survival

FIGURE 4

FIGURE 4

Observed incidence rate ratios (IRR) from simulation models for all cancers in the scenario with both the competing risk of death and selective survival across varying values for U (prevalence, effect on cancer mortality, and effect on dementia incidence). Effect of cancer on mortality was defined by age-specific relative survival (SEER)

FIGURE 5

FIGURE 5

Prevalence of U among those surviving dementia free, stratified by history of cancer in the all-cancers model in the scenario with both the competing risk of death and selective survival (prevalence of U = 0.30, IRRU-cancer mortality = 0.70, IRRU-dementia = 0.70)

FIGURE 6

FIGURE 6

Observed cumulative incidence ratios (CIR) in the simulation model with (A) competing risk of death only, and (B) competing risk of death and selective survival, showing reduced lifetime risk, rather than rate, of dementia in cancers with higher mortality (all cancers and lung cancer)

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