Association of cancer history with structural brain aging markers of Alzheimer's disease and related dementias risk

INTRODUCTION: Cancer survivors are less likely than comparably aged individuals without a cancer history to develop Alzheimer's disease and related dementias (ADRD). METHODS: In the UK Biobank, we investigated associations between cancer history and five structuralmagnetic resonance imaging (MRI) markers forADRDrisk, using linearmixed-effects models to assess differences in mean values and quantile regression to examine whether associations varied across the distribution ofMRI markers. RESULTS: Cancer history was associated with smaller mean hippocampal volume (b=19 mm3, 95% CI = -36, -1) and lower mean cortical thickness in the Alzheimer's disease signature region (b = -0.004 mm, 95% CI = -0.007, -0.000). Quantile regressions indicated individuals most vulnerable to ADRD were more affected by cancer history. DISCUSSION: Some brain MRI markers associated with ADRD risk were elevated in adults with a history of cancer. The magnitude of the adverse associations varied across quantiles of neuroimaging markers, and the pattern suggests possible harmful associations for individuals already at high ADRD risk.