Is there a link between cancer and Alzheimer disease ?

Neurology 2010;74:100–101 Cancer and Alzheimer disease (AD) are common age-related conditions. Cancer arises from dysfunction of genetic and epigenetic processes that control cellular differentiation and proliferation. Recent data suggest that molecular machinery that is involved in maintaining neural function in neurodegenerative disease may be shared with oncogenetic pathways. For example, some studies suggest that cancer incidence is lower among persons with Parkinson disease.1 Few data are available regarding a link between cancer and AD.2 However, the presence of an association could further stimulate investigations related to molecular changes underlying neurodegenerative diseases. In this issue of Neurology, Roe et al.3 use data from the Cardiovascular Health Cognition Study to investigate the relationship between cancer and AD. The Cardiovascular Health Study is a populationbased cohort study of nearly 5,900 persons. The Cognition Study is an ancillary study of about 3,600 persons who had an MRI brain scan and completed annual brief cognitive testing for up to 5 years. Several years later, subjects were divided into highand low-risk groups for dementia based on cognitive tests available in the Cardiovascular Health Study. A sample of surviving high-risk white subjects, and all minorities, were invited to participate in a clinical evaluation. Medical records were obtained for deceased participants and those who refused the evaluation. Records were adjudicated for diagnoses of prevalent and incident dementia and its subtypes, and mild cognitive impairment (MCI). Prevalent cancer was based on self-report. Incident cancer was based on hospitalization records with surveillance over more than 8 years. For these analyses, persons with MCI were excluded, leaving about 3,000 persons. The authors first examined the relation of prevalent dementia to incident cancer. Among 165 persons with prevalent dementia and 2,107 persons without prevalent dementia, there were 376 cases of incident cancer. After adjustment for relevant covariates, prevalent AD was associated with a 60% reduced risk of incident cancer. Prevalent vascular dementia was not associated with cancer incidence. The second set of analyses examined the relation of prevalent cancer to incident dementia separately for white and minority subjects. Among 423 persons with prevalent cancer (394 white and 29 minority subjects) and 1,973 persons without prevalent cancer (1,768 white and 205 minority subjects), there were 478 cases of incident dementia. After adjustment for relevant covariates, prevalent cancer was associated with a 30% reduced risk of incident AD among white subjects, whereas the association in minority subjects was in the opposite direction, but not significant. No association was found between prevalent cancer and incident vascular dementia. The study has a number of limitations, many of which were acknowledged by the authors. For example, the authors used hospital records to identify incident cancer cases. Patients with dementia tend to be diagnosed with cancer at a later stage, have significantly higher cancer mortality rates, and may not be hospitalized as frequently for cancer relative to those without dementia.4 This could result in the appearance of a reduced incidence of cancer among those with dementia. The findings on incident dementia are less prone to bias because the diagnoses are based in part on a clinical evaluation. However, since all minority subjects were evaluated clinically whereas only a sample of white subjects were evaluated, there may have been better dementia case finding among minority subjects. Further, data suggest that racial and ethnic minorities are diagnosed with cancer at a later stage of illness and have higher cancer mortality rates.5 These factors could account in part for the reported racial differences. Both cancer and dementia are associated with an increased risk of death. Treating cancer-free mortality among those with dementia, and dementia-free mortality among those with cancer, as censoring events in a conventional Cox proportional hazards