Inverse occurrence of cancer and Alzheimer disease

Musicco, Massimo; Adorni, Fulvio; Santo, Simona Gabriella Di; Prinelli, Federica; Pettenati, Carla; Caltagirone, Carlo; Palmer, Katie; Russo, Antonio

doi:10.1212/wnl.0b013e31829c5ec1

Cited by 251 publications

(274 citation statements)

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“…We offer several cautions about this analysis. The findings are heavily weighted by a single study (Musicco et al, 2013), and therefore, their conclusions largely reflect this one study's findings. In addition, the meta-analysis does not correct for model misspecification or ignoring potential confounders, and the time-varying nature of cancer diagnosis relative to an AD diagnosis.…”

Section: Discussionmentioning

confidence: 84%

“…These findings would therefore lead investigators to conclude that these psychosocial risk factors lead to increased risk of both diseases. However, several epidemiological studies have examined the association between cancer and AD and have concluded that there may be an inverse association between these two diseases-specifically, that a cancer diagnosis reduces the risk of subsequent AD (Driver et al, 2012;Frain et al, 2013;Musicco et al, 2013;Roe, Behrens, Xiong, Miller, & Morris, 2005;Roe et al, 2010;White, Lipton, Hall, & Steinerman, 2013). The authors of these studies and subsequent reviews have suggested a possible biological mechanism underpinning both diseases that leads to two opposite cellular functions-cellular proliferation (predisposing to cancer) or cellular apoptosis (predisposing to AD) (Behrens, Lendon, & Roe, 2009;Driver, 2014;Tabares-Seisdedos & Rubenstein, 2013).…”

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confidence: 99%

“…These studies are limited by relatively short follow-up periods (Frain et al, 2013;Musicco et al, 2013;Roe et al, 2005Roe et al, , 2010White et al, 2013), small sample sizes (Driver et al, 2012;Roe et al, 2005Roe et al, , 2010White et al, 2013), reliance primarily upon prescription data for AD diagnoses (Musicco et al, 2013), and in one case a predominantly (98%) male patient population (Frain et al, 2013). Figure 1 displays the hazard rate ratios (HRs) and 95% confidence intervals (CIs) for the five published studies examining this association.…”

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confidence: 99%

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Is Cancer Protective for Subsequent Alzheimer’s Disease Risk? Evidence From the Utah Population Database

Hanson

Horn

Rasmussen

et al. 2016

GERONB

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Objective: Several studies have suggested that cancer is associated with a reduced risk of the development of Alzheimer's disease (AD). This study seeks to improve our understanding of the association between cancer and the development of AD by showing how mortality selection alters this relationship. Method: A retrospective cohort study was carried out examining 92,425 individuals (47,873 women and 44,552 men) from the Utah Population Database with and without a history of any primary cancer identified by the Utah Cancer Registry. All individuals were aged 65-79 years and free of dementia in 1992 and followed for upwards of 18 years (1992-2009) for AD ascertainment, which was identified using diagnostic information from Medicare claims data. Results: We replicate previous results suggesting that cancer is associated with reduced risk of subsequent AD under specific statistical model specifications. However, these results should not be interpreted as evidence of an etiological association. We conclude that higher rates of overall mortality among individuals with cancer relative to those without cancer induce the widely reported putative protective association with cancer. Conclusion: Careful consideration of model specification and the profound effects of mortality selection in the older adult population is essential when investigating the relationship between aging-related diseases such as cancer and AD. We show that cancer does not provide protection from AD as previously described in the literature. Social scientists seeking to understand social disparities in disease outcomes among older adults may therefore want to strongly consider the role of mortality selection which, if uncorrected, may generate biased associations.

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confidence: 84%

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Is Cancer Protective for Subsequent Alzheimer’s Disease Risk? Evidence From the Utah Population Database

Hanson

Horn

Rasmussen

et al. 2016

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“…Interestingly, several studies have consistently shown an inverse link between the 2 diseases. Patients with dementia have a decreased risk of cancer [1-7], while persons with a history of cancer are affected less often from subsequent dementia [1, 2, 4, 5, 8]. …”

Section: Introductionmentioning

confidence: 99%

Mild Cognitive Impairment and Dementia Show Contrasting Associations with Risk of Cancer

et al. 2018

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Background: To investigate and to compare the relation between dementia and cancer with the association between mild cognitive impairment (MCI) and cancer. Methods: A total of 13,207 persons from the Rotterdam Study were followed between 1990 and 2013 for the onset of dementia and cancer (sample 1). Between 2002 and 2005, a subset of 5,181 persons underwent extensive cognitive testing for MCI and subsequently were followed up for cancer until 2013 (sample 2). We used Cox proportional hazard models to determine the association between dementia and cancer, and MCI and cancer. Results: In sample 1, 1,404 patients were diagnosed with dementia, and 2,316 developed cancer (63 among dementia cases). Dementia was associated with a decreased risk of cancer (hazard ratio [HR] 0.53; 95% CI 0.41–0.68). In sample 2, 513 persons were diagnosed with MCI and 670 persons developed cancer (81 among MCI cases). In contrast to individuals with dementia, those with MCI tended to have an increased risk of cancer (HR 1.25; 95% CI 0.99–1.58). Conclusions: We found that persons with MCI tended to have an increased risk of cancer, whereas those with dementia have a decreased risk. These findings call into question a biological explanation for the inverse link between dementia and cancer, thereby suggesting the presence of methodological bias.

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“…Heterogeneity was assessed using Cochran's Q test and I 2 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] .…”

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

et al. 2014

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Letter to the Editor 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 I 2 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 [5-9] , we observed a significantly reduced risk of cancer in AD individuals [effect size (ES) = 0.50; 95% CI 0.34-0.74; I 2 = 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; I 2 = 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. Disclosure StatementThe 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.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 ...

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Inverse occurrence of cancer and Alzheimer disease

Cited by 251 publications

References 15 publications

Is Cancer Protective for Subsequent Alzheimer’s Disease Risk? Evidence From the Utah Population Database

Is Cancer Protective for Subsequent Alzheimer’s Disease Risk? Evidence From the Utah Population Database

Mild Cognitive Impairment and Dementia Show Contrasting Associations with Risk of Cancer

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

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