With age comes disease. Cancer and Alzheimer鈥檚 dementia are among the commonest and most feared health conditions 鈥 particularly in countries with ageing populations such as the 好色先生. Several decades ago, researchers at a psychiatric centre in New York between these two diseases. , they found an inverse relation between cancer and Alzheimer鈥檚 disease.
In one of the first epidemiological studies on the topic Jane Driver of Brigham and Women鈥檚 Hospital in Boston, Massachusetts in the US followed 1,278 participants aged 65 and older for a mean of 10 years. , the results showed that cancer survivors had a 33% decreased risk of subsequently developing Alzheimer鈥檚 disease compared with people without a history of cancer.
As intriguing as the finding was, the scientific community urged caution and pointed out potential pitfalls in dealing with age-related diseases. One of them concerned a so-called survival-bias: perhaps people with a history of cancer simply do not live long enough to develop Alzheimer鈥檚 disease.
Since then, scientists around the world have analysed the relationship between cancer and Alzheimer鈥檚 disease in more detail and built an increasingly compelling case. In the , published in July this year, researchers at Imperial College London provide convincing evidence of a lower incidence of dementia following a cancer diagnosis. They looked at the NHS health data of more than three million people aged 60 and over and followed them for a mean period of 9.3 years, taking extra care to correct for potential biases. Their results show that cancer survivors have a 25% lower risk of developing age-related dementia compared with people without a history of cancer. The inverse association was observed for the most common types of cancers such as prostate, colon, lung and breast.
鈥淭he relationship between cancer and Alzheimer鈥檚 disease is very intriguing and it鈥檚 persistent,鈥 says Erin Abner, a professor at the University of Kentucky. 鈥淎 lot of people questioned the results and tried hard to find other explanations for the inverse association, but it just keeps showing up, even after taking confounding factors into account.鈥
Two years ago, Abner published for the inverse association. Unlike previous epidemiological studies, she looked at brain autopsies of patients at the University鈥檚 Alzheimer鈥檚 Disease Research Center. 鈥淲e found a pretty consistent association between someone having had cancer and having lower levels of amyloid pathology in their brain, which is a hallmark of Alzheimer鈥檚 disease,鈥 she says.
In her study the inverse association was seen only with Alzheimer鈥檚 disease and not with dementia in general. In contrast, many of the previous epidemiological studies did not differentiate between Alzheimer鈥檚 and other age-related dementias. The majority of elderly patients with dementia, however, have Alzheimer鈥檚.
But that is not the whole story; there is another twist to the inverse relationship. Not only do those with a history of cancer have a decreased risk of dementia, but those with Alzheimer鈥檚 disease are less likely to develop cancer. In her 2012 study Jane Driver reported that the inverse relation goes in both directions, a finding that was looking at more than one million residents, and more recently in South Korea. According to , patients with Alzheimer鈥檚 disease show a 37% lower likelihood of developing overall malignancy compared to those without dementia. Again, the finding was met with scepticism. Perhaps, critics argued, people with dementia were less likely to be screened for cancer given the potentially limited benefit of therapies.
鈥淭he results have been replicated again and again, and most experts in the field now believe the inverse relation appears to be real,鈥 says Elio Riboli who led the study at Imperial College London that also confirmed the bidirectionality. 鈥淭he next step is to understand the biology behind this phenomenon.鈥
Some researchers have suggested that cancer treatment itself may be having an effect on dementia risk. In recent years, inflammation has emerged as a central process in the onset and progression of Alzheimer鈥檚 disease, so it is possible that chemotherapy may be protecting neurons by suppressing inflammation.
But for Elio Riboli, that is not the whole story. The fact that the inverse relationship is bidirectional suggests there may be underlying biological mechanisms that influence the two groups of diseases in opposite directions. The researchers at Imperial College performed genetic analyses. 鈥淟ooking at hundreds of genes, we identified a genetic profile that predicts an increased risk of cancer and we found that this profile is tied to a lower risk of dementia.鈥
According to Riboli, the specific genetic factors may be involved in tissue regeneration. 鈥淕rowth factors are a large family of molecules that regulate tissue renewal and growth. They are generally associated with better cardiovascular health,鈥 he says. 鈥淗aving a genetic makeup that favours replication allows for better renewal of tissues and arteries, but may also slightly increase the risk of some cancers.鈥
Surprising findings can open new lines of research, says Riboli. For instance, it has long been known that people with diabetes have an increased risk of developing cancer, with : men with diabetes have a 10-20% reduced risk of developing prostate cancer. 鈥淲hy does being diabetic come with a reduced risk of prostate cancer, a cancer for which we are desperately trying to understand the risk factors?鈥 asks Riboli. Similarly, research into the inverse association between cancer and dementia may shed light on new molecular pathways that contribute to, or protect people from, the development of dementia. 鈥淵ou open a window and suddenly you see a new horizon,鈥 he says.
Cancer is linked to uncontrolled cell growth, whereas dementia is tied to excessive neuronal death. Mikyoung Park of the Korea Institute of Science and Technology in Seoul, South Korea, recently published a of molecular mechanisms that operate inversely in cancer and neurodegeneration 鈥 some leading to enhanced resistance to cell death and others to a higher risk of cell death. Dysfunctional mitochondria, the cellular power plants, might provide a crucial link between cancer and neurodegeneration, a decade ago by Jane Driver and Lloyd Demetrius, based on mathematical arguments.
Unravelling the inverse association between cancer and neurodegenerative diseases may ultimately help treat or prevent these common conditions. But many questions remain unanswered. 鈥淏oth cancer and dementia are actually a bunch of different diseases,鈥 says Erin Abner. 鈥淲e don鈥檛 have the granularity of data to draw strong conclusions about any one type of disease.鈥 Additionally, there is a long latency period between the development of pathology and the start of symptoms, both in cancer and Alzheimer鈥檚, raising questions around the timing of this inverse relation.
These enigmatic findings have no practical relevance for the time being. 鈥淏ut even now, it may be just a little piece of comfort for cancer survivors, that something is going to be a bit easier for them down the road,鈥 says Abner.
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