Association of cancer with neuropathological markers of Alzheimer's disease and related dementias.

INTRODUCTION: We assessed associations of cancer diagnoses with neuropathology of Alzheimer's disease (AD) and related dementias. METHODS: We retrieved 2288 cases from the National Alzheimer Coordinating Center (NACC) cohort with available information on cancer diagnoses and neuropathological scoring of Braak stages, Thal amyloid phases, neuritic plaques, TDP-43 pathology, and Lewy body pathology. We used Bayesian ordinal regression to assess associations of prevalent or incident cancer diagnoses with global cognition and postmortem neuropathological scores. RESULTS: We found extreme evidence (Bayes factor [BF] > 2000) that both prevalent and incident cancer diagnoses were associated with better global cognition, strong evidence (BF = 26) for an association of a prevalent cancer diagnosis with lower TDP-43 pathology, and weak evidence (BF = 3.2) for an association with lower Lewy body pathology. DISCUSSION: Our data suggest that selective survival and biological effects may contribute to the lower risk of dementia in people with a cancer diagnosis. Highlights: A prevalent diagnosis of cancer was associated with a lower risk of cognitive decline in older individuals.A prevalent diagnosis of cancer was associated with a lower risk of TDP-43 pathology and Lewy body pathology in older individuals.Effects of cancer on TDP-43 pathology were maintained when controlling for degree of cognitive decline.