Risk of Alzheimer's disease or dementia following a cancer diagnosis

by Erin J. Aiello Bowles, Rod L. Walker, Melissa L. Anderson, Sascha Dublin, Paul K. Crane, Eric B. Larson

We evaluated dementia and Alzheimer’s disease (AD) risks after a cancer diagnosis in a population-based prospective cohort, the Adult Changes in Thought (ACT) study.

We followed community-dwelling people aged ≥65 years without dementia at study entry for incident dementia and AD from 1994–2015. We linked study data with cancer registry data and categorized cancer diagnoses as prevalent (diagnosed before ACT study enrollment) or incident (diagnosed during follow-up). We used Cox regression to estimate cause-specific hazard ratios (HRs) with 95% confidence intervals (CIs) for dementia or AD risk comparing people with a cancer diagnosis to people without cancer. We conducted sensitivity analyses restricted to people surviving beyond age 80, and stratified by cancer stage, type, and whether the cancer was smoking-related.

Among 4,357 people, 756 (17.4%) had prevalent cancer; 583 (13.4%) developed incident cancer, 1,091 (25.0%) developed dementia, and 877 (20.1%) developed AD over a median 6.4 years (34,482 total person-years) of follow-up. Among complete cases (no missing covariates) with at least one follow-up assessment, adjusted HRs for dementia following prevalent and incident cancer diagnoses were 0.92 (95%CI: 0.76, 1.11) and 0.87 (95%CI: 0.64, 1.04), compared to no cancer history. HRs for AD were 0.95 (95%CI: 0.77, 1.17) for prevalent cancer and 0.73 (95%CI: 0.55, 0.96) for incident cancer. In sensitivity analyses, prevalent late-stage cancers were associated with reduced risks of dementia (HR = 0.51, 95%CI: 0.30, 0.89) and AD (HR = 0.50, 95%CI: 0.27, 0.94). When limited to people who survived beyond age 80, incident cancers were still associated with reduced AD risk (HR = 0.69, 95%CI: 0.51, 0.92).

Our results do not support an inverse association between prevalent cancer diagnoses, which were primarily early-stage, less aggressive cancers, and risk of dementia or AD. A reduced risk of AD following an incident cancer diagnosis is biologically plausible but may reflect selective mortality.