Alzheimer’s Disease May Protect Against Cancer and Vice Versa

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As we get older, and care for our parents as they get older, the most feared age-related conditions we face are arguably Alzheimer’s disease and cancer. But researchers at Washington University have just shown that at least we don’t have to fear both of them at the same time; they recently published a paper in the medical journal of the American Academy of Neurology demonstrating that people with Alzheimer’s disease have a significantly reduced risk of being hospitalized for cancer [1].

This potential link between these two diseases had been noted for some time, but in this study researchers devoted considerable effort to overcoming the limitations in their previous work. Firstly, they used a population-based sample of 3,020 people older than 65, so their results were not limited to a particular geographic area or socio-economic segment of society. Secondly, they used hospital records rather than informant reports to quantify cancer diagnoses. This controlled for the risk that people with Alzheimer’s disease may be less likely to report their cancers than those without. And lastly, to ensure that they were not seeing less cancer in Alzheimer’s patients because physicians were less likely to look for cancer in people with dementia, or because people with dementia simply die earlier than those without it and thereby avoid cancer, they also looked at cancer risk among people with vascular dementia. Vascular dementia is not neurodegenerative in origin; rather, it results from brain damage due to vascular pathology.

Cox proportional hazards models are a subclass of statistical survival models that relate the time of an event, usually death or failure, to a number of descriptive variables known as covariates, which in this study was time to first cancer hospitalization and time to first diagnosis of dementia. The researchers conducted two studies using the date of brain MRI (done in 1992-1993 for all participants) as a baseline. They first investigated whether time from baseline to first cancer hospitalization was associated with having dementia (including vascular dementia) at baseline using Cox proportional hazards models. They then used the statistical models to determine whether the time from baseline to first diagnosis of dementia (including vascular dementia) was related to having a cancer history at baseline. Participants were followed for an average five years to see if they developed dementia and an average of eight years to see if they developed cancer.

At the beginning of the study (baseline), 165 participants had Alzheimer’s disease and 522 participants had cancer. During the study, 478 participants developed dementia and 376 participants developed cancer. The researchers found that participants who had Alzheimer’s disease at baseline had a 69% reduction in cancer risk compared to participants that did not have Alzheimer’s disease.

For white participants who had cancer at baseline, the risk of developing Alzheimer’s disease was reduced by 43% compared to participants that did not have cancer. The opposite effect was observed for minority populations: minority participants who had cancer at the beginning of the study were more likely to develop Alzheimer’s disease than minority participants that didn’t have cancer. Although this result was statistically significant, only 29 minority participants had a cancer history at baseline; thus, the researchers can not exclude the possibility the finding is incorrect.

The fact that Alzheimer’s disease has a reciprocal relationship with cancer whereas vascular dementia does not implies that it is neurodegeneration, and not cognitive impairment, that provides the protection from cancer. This idea is bolstered by findings that people with Parkinson’s disease, another age-associated neurodegenerative disorder, also have a decreased risk of most cancers [2]. And it makes sense upon consideration of the natures of the two diseases. Cancer is a disorder of uncontrolled growth and/or a lack of timely cell death; Alzheimer’s and Parkinson’s, in contrast, are caused by vast swaths of inappropriate neuronal cell death. It stands to reason that genetic or environmental factors that promote one condition would suppress the other.

Cell survival in cancer and Parkinson’s disease

In fact, there is experimental evidence indicating that cancer and Parkinson’s disease share some of the same underlying genetic pathways, specifically those that regulate cell survival. A good example is the pathway that hinges on the tumor suppressor Phosphatase and tensin homolog (PTEN), one of the most commonly mutated genes in human cancers [3]. When the expression of PTEN is lost, there is an increase in cell proliferation and cancer results; when PTEN is over-expressed there is rampant apoptosis (programmed cell death) like that seen in the neurodegenerative disorders. There are also a number of genes associated with the familial form of Parkinson’s disease that regulate cell death that have been shown to play roles in tumorigenesis.

Studies of this kind are valuable because identifying such associations between conditions can ultimately help in defining the mechanisms responsible for each, which is a key step in finding therapeutic targets. And then everyone, even those not suffering from Alzheimer’s disease or cancer, will have less to fear.

References

1. Roe et al. Cancer linked to Alzheimer disease but not vascular dementia. Neurology 74: 106-112, 2010. DOI: 10.1212/WNL.0b013e3181c91873
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2. Driver et al. A prospective cohort study of cancer incidence following the diagnosis of Parkinson’s disease. Cancer Epidemiol Biomarkers Prev 16(6): 1260-1265, 2007.
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3. Kim et al. Tumours and tremors: how PTEN regulation underlies both. British Journal of Cancer 94: 620-624, 2006.
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