Alzheimer's Disease and Cancer: Current Epidemiological Evidence for a Mutual Protection

With the rapid (and unprecedented) population aging and growth worldwide, Alzheimer's disease (AD) and cancer have become two of the most important global public health problems [1,2]. Therefore, a better understanding of the connections and interactions between these disorders could potentially improve the quality of life and healthcare outcome of millions worldwide [3]. However, the comorbidity between AD and cancer is not completely understood. This is particularly reflected by the ongoing debate concerning a lower-than-expected probability of cancer developing in patients with AD and vice versa [4]. For example, Musicco et al. [5] have recently found that individuals with cancer are at a lower risk of developing AD compared to those without cancer (a relative risk reduction of 35%). A similar but more pronounced reduction of cancer risk was identified in patients with AD (43%).To further validate and quantify these epidemiological findings, we comprehensively searched all observational noninterventional studies published (up to July 2013) reporting valid measures of the comorbidity-related risk of AD and cancer, primarily based on a previous review (methods are described elsewhere) [4]. Briefly, studies were selected if they met the following criteria: (a) cohort and/or nested case-control study evaluating the association between cancer and AD, and (b) reporting of an estimate of association (e.g. relative risk, standardized incidence ratio, or hazard ratio) with measures of variation (e.g. confidence intervals). We included epidemiological studies performed in the general population and/or in healthcare settings (e.g. population or hospital-based studies). According to design, we used the investigator-reported disease definitions. Estimates from each epidemiological study were pooled using the inverse variance method with both fixed and random effects models. Heterogeneity was assessed using Cochran's Q test and I2 statistic. All the analyses were conducted using Stata 12 (StataCorp LP, College Station, Tex., USA).Five reports [5,6,7,8,9] contained valid information on the comorbidity between AD and cancer. All patient data were collected from population or community-based registries in 5 longitudinal studies [5,6,7,8,9]. The number of AD patients in each study ranged from 221 to 6,960. Three studies were based in the United States and 1 in Europe (Italy) and Asia (Taiwan), respectively. By pooling the eligible epidemiological studies [5,6,7,8,9], we observed a significantly reduced risk of cancer in AD individuals [effect size (ES) = 0.50; 95% CI 0.34-0.74; I2 = 90.5%; Q statistic p value <0.001; fig. 1]. We also found that there was a significantly decreased risk of AD in the cancer cohort relative to controls (ES = 0.64; 95% CI 0.56-0.73; I2 = 0.0%; Q statistic p value = 0.76; fig. 1).These significant findings lend support to the concept of a mutual protection between AD and cancer. These lower risks could be associated with diverse and nonmutually exclusive factors to do with clinical or environmental factors. However, there are also biological explanations (based on the pathogenesis of neurodegeneration) that cannot be ruled out [4,10]. For instance, identifying common mechanisms of inverse comorbidity may potentially lead to a better understanding of both diseases and could foster the development of novel and more effective intervention programs for these burdensome conditions in human populations.The authors state that there is no conflict of interest. The views expressed are those of the authors and should not be understood or quoted as being made on behalf of or reflecting the position of any institution.