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. 2024 Nov;20(11):7902-7912.
doi: 10.1002/alz.14268. Epub 2024 Sep 26.

The inverse association between cancer history and incident cognitive impairment: Addressing attrition bias

Michelle Shardell  1   2 , Alan M Rathbun  2 , Ann Gruber-Baldini  2 , Alice S Ryan  3 , Jack Guralnik  2 , Dimitrios Kapogiannis  4 , Eleanor M Simonsick  4
Affiliations

The inverse association between cancer history and incident cognitive impairment: Addressing attrition bias

Michelle Shardell et al. Alzheimers Dement. 2024 Nov.

Abstract

Introduction: Cancer is inversely associated with cognitive impairment. Whether this is due to statistical handling of attrition (death and censoring) is unknown.

Methods: We quantified associations between cancer history and incident cognitive impairment among Health, Aging, and Body Composition Study participants without baseline cognitive impairment or stroke (n = 2604) using multiple competing-risks models and their corresponding estimands: cause-specific, subdistribution, and marginal hazards, plus composite-outcome (cognitive impairment or all-cause mortality) hazards. All-cause mortality was also modeled.

Results: After covariate adjustment (demographics, apolipoprotein E ε4, lifestyle, health conditions), cause-specific and marginal hazard ratios (HRs) were similar to each other (≈ 0.84; P values < 0.05). The subdistribution HR was 0.764 (95% confidence interval [CI] = 0.645-0.906), and composite-outcome Cox model HR was 1.149 (95% CI = 1.016-1.299). Cancer history was positively associated with all-cause mortality (HR = 1.813; 95% CI = 1.525-2.156).

Discussion: Cause-specific, subdistribution, and marginal hazards models produced inverse associations between cancer and cognitive impairment. Competing risk models answer slightly different questions, and estimand choice influenced findings here.

Highlights: Cancer history is inversely associated with incident cognitive impairment. Findings were robust to handling of competing risks of death. All models also addressed possible informative censoring bias. Cancer history was associated with 16% lower hazard of cognitive impairment. Cancer history was associated with 81% higher all-cause mortality hazard.

Keywords: cancer; censoring; competing risks; sensitivity analysis; time‐to‐event analysis.

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Conflict of interest statement

The authors have no conflicts of interest to declare. Author disclosures are available in the supporting information.

Figures

FIGURE 1
FIGURE 1
Directed acyclic graph conveying selective survival and informative censoring biases. Dashed lines are relationships distorted by conditioning on being alive and uncensored. Red line is the relationship of interest. Variable v refers to visit number.
FIGURE 2
FIGURE 2
Nine‐year cumulative incidence of all‐cause mortality (death), cognitive impairment, and combined prevalence and cumulative incidence of cancer history. Left: Cumulative incidence of all‐cause mortality by prevalent (baseline) cancer history status. P value from logrank test. Table shows cumulative number of deaths and number remaining at risk. Right: Cumulative incidence of cognitive impairment by prevalent cancer history status. P value from a Gray test. Table shows cumulative number of incident cognitive impairment cases and number remaining at risk. Combined prevalence and cumulative incidence of cancer history. Table shows cumulative number of prevalent and incident cancer history cases and number remaining at risk.
See this image and copyright information in PMC

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