Aging is related both to an increased risk of Alzheimer’s disease (AD) and cancer, two life‐threatening diseases. Several studies have reported a bidirectional inverse association between AD and cancer such that cancer risk was lower in AD patients and vice versa . Several biologic mechanisms have been hypothesized to underlie this inverse relationship between the two diseases, including regulation of the cell cycle, with signaling pathways regulating cell death on one hand and proliferation on the other . Molecular mechanisms have also been hypothesized; for example, the enzyme Pin1 may be overactivated in many cancers and inactivated in AD brains Yet, whether previously observed associations reflect pathophysiologic processes rather than intrinsic limitations of epidemiologic studies remains uncertain.
An alternative explanation of the inverse association finding is ascertainment bias such that AD is less likely to be diagnosed in people with cancer, and cancer is less likely to be diagnosed in AD patients. There are special challenges in assessing the relationship between cancer and AD, as both diseases may lead to physical disabilities and AD patients are cognitively impaired. Screening or even diagnostic tests for cancer may be diminished among those already compromised by cognitive impairment The intensity of medical surveillance could also influence diagnosis of cancer or AD. In addition, the relative rarity of combined cases of AD and specific cancers requires a large study population to examine associations by cancer site, including cancers which are often detected by screening.
To address these limitations and explore the relationship between AD and overall cancer as well as with specific cancer sites, we used data from a large group of Medicare patients residing within the population‐based Surveillance, Epidemiology and End‐Results (SEER) Program registry areas. We examined the risk of incident cancer after an AD diagnosis, as well as the risk of a first AD diagnosis in cancer survivors, while controlling for frequency of physician visits, a surrogate for medical surveillance. We further used a group of patients with automobile injuries as a negative control because there is no apparent biologic relationship between automobile accidents and cancer diagnoses. This allowed us to explore biases in ascertaining one serious medical condition in individuals already experiencing another