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

OBJECTIVE 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. METHODS 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. RESULTS 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). CONCLUSIONS 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.