Could the conflicting elements hidden in the biological mechanisms of the two diseases be the key to treatment?
Patients with a history of cancer have a lower risk of developing Alzheimer’s disease, and patients with Alzheimer’s disease have a lower risk of developing cancer. This inverse relationship suggests that opposing factors are at work in the biological mechanisms of the two diseases, and may ultimately be the key to discovering a cure. This is what the Guardian reported on the 16th (local time) based on a paper by researchers at Imperial College London (ICL) in the UK published in the Journal of Prevention of Alzheimer’s Disease.
Decades ago, researchers at a psychiatric center in New York, USA, observed an interesting relationship between these two diseases. After autopsies, they found an inverse relationship between cancer and Alzheimer’s disease.
In one of the first epidemiological studies on this topic, Dr. Jane Driver of Brigham and Women’s Hospital and professor of medicine at Harvard University followed 1,278 participants aged 65 and older for an average of 10 years. The study, published in 2012, found that cancer survivors had a 33% lower risk of developing Alzheimer’s disease compared to people without a history of cancer.
Although it was an interesting research result, academic circles downplayed its significance. The main evidence was the so-called ‘survival bias’, which suggests that people with a history of cancer may not live long enough to develop Alzheimer’s disease.
ICL researchers present convincing evidence that the risk of dementia is lowered after a cancer diagnosis
The ICL research team’s paper published in July of this year presented convincing evidence that the incidence of dementia is low after a cancer diagnosis through the largest-ever study. More than 3 million British people aged over 60 were followed for an average of 9.3 years and found that cancer survivors had a 25% lower risk of developing age-related dementia compared to people without a history of cancer. Inverse associations were observed in all of the most common types of cancer: prostate, colon, lung, and breast.
“The relationship between cancer and Alzheimer’s disease is very interesting and persistent,” said Erin Abner, a professor at the Alzheimer’s Disease Research Center at the University of Kentucky. “Professor Abner presented clinical evidence of an inverse correlation through brain autopsy results of Alzheimer’s disease patients two years ago,” he said. “We found that people with cancer had lower levels of amyloid protein pathology in the brain. “We found a very consistent correlation between the two,” he said, adding, “High levels of amyloid protein pathology are a hallmark of Alzheimer’s disease.”
However, the inverse association was limited to Alzheimer’s disease and did not appear to apply to general dementia. However, most elderly people with dementia are Alzheimer’s disease patients.
There is another twist to this inverse proportionality. Not only do people with a history of cancer have a reduced risk of dementia, but people with Alzheimer’s disease have a lower risk of developing cancer. Professor Jane Driver pointed out in a 2012 study that the inverse proportionality goes both ways and was repeated in the results of a study of more than 1 million residents in northern Italy and a recent study of Koreans. A study in Korea showed that patients with Alzheimer’s disease had a 37% lower risk of developing malignant tumors compared to patients without dementia.
A counterargument was raised regarding these recent research results, saying that it is because the likelihood of Alzheimer’s disease patients receiving cancer screening is still low. But Professor Elio Rivoli, a cancer epidemiologist at ICL who led the study in the UK, said: “The results have been replicated over and over again, and most experts now believe that the inverse relationship appears real. The next step is the biology behind this phenomenon. “It is about understanding,” he said.
Is cancer treatment itself bad for dementia?…”Genes that increase cancer risk can reduce dementia risk.”
Some researchers have speculated that cancer treatment itself may affect dementia risk. Since inflammation has emerged as a central process in the onset and progression of Alzheimer’s disease in recent years, the hypothesis is that chemotherapy has the potential to protect neurons by suppressing inflammation.
But for Professor Rivoli, he is not the whole picture. The fact that the inverse relationship is bidirectional suggests that there may be underlying biological mechanisms affecting the two disease groups in opposite directions. “By analyzing hundreds of genes, we identified gene types predicted to increase cancer risk and found that these types were associated with a reduced risk of dementia,” the ICL researchers said.
According to Professor Rivoli, certain genetic factors may be involved in tissue regeneration. “Growth factors are a large group of molecules that regulate tissue regeneration and growth,” he said. “This group of molecules is generally associated with better cardiovascular health.” “Having a genetic makeup that favors replication may lead to better tissue and artery regeneration, but it may also slightly increase the risk of some cancers,” he explained.
This surprising discovery could open up new research directions, Professor Rivoli said. For example, it has long been known that people with diabetes are at increased risk of developing cancer. A notable exception is the 10 to 20 percent reduced risk of developing prostate cancer in men with diabetes.
Professor Rivoli asked, “Why does having diabetes reduce the risk of prostate cancer?” He also explained that research on the inverse relationship between cancer and dementia could reveal new molecular pathways that contribute to the development of dementia or protect people.
Cancer is associated with uncontrolled cell growth, while dementia is associated with excessive nerve cell death. Dr. Mi-kyung Park of the Korea Institute of Science and Technology (KIST) Seoul Research Institute recently published a review paper on the molecular mechanisms that work inversely in cancer and neurodegeneration. Some of these have been shown to increase resistance to cell death, while others increase the risk of cell death. Dysfunction of mitochondria, the cell’s powerhouse, may provide an important link between cancer and neurodegeneration. This is a hypothesis presented 10 years ago by Professor Jane Driver and Professor Lloyd Demetrius, a theoretical biologist and mathematician at Harvard University, based on mathematical arguments.
Additional research is needed on when and why the inverse relationship occurs
Uncovering the inverse relationship between cancer and neurodegenerative diseases may ultimately help treat or prevent these diseases. But many questions remain unanswered. “Cancer and dementia are actually two different diseases,” Abner said. “We don’t have the granular data to make strong conclusions about one type of disease.” Additionally, since both cancer and Alzheimer’s disease have long delays between pathological development and the onset of symptoms, the timing of this inverse proportion is also questioned.
Therefore, these puzzling research results have no practical significance for the time being. “But it may be comforting to cancer survivors now that it will help solve problems in the future,” Professor Abner said.
Source: kormedi.com