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Cancer, chemotherapy reduce Alzheimer’s risk, study finds

A sweeping study from Boston scientists finds that survivors of many cancers appear to have a significantly reduced risk of developing Alzheimer’s disease, especially those treated with chemotherapy.

The results reported Monday generated buzz among scientists about possible new approaches to fighting the mind-robbing illness, including treatment with some variation of chemotherapy. The connection between the diseases also points to little-explored triggers for Alzheimer’s that could be targeted by researchers trying to develop medications.

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Researchers at the VA Boston Healthcare System found that most types of cancer were associated with a reduced risk of Alzheimer’s, which has no cure. Survivors of liver cancer had the most protection, a 51 percent reduced risk.

Cancers of the pancreas, esophagus, lung, and kidney, as well as leukemia, also appeared to be “protective,” reducing risk between 22 and 44 percent, according to the study presented at the Alzheimer’s Association International Conference in Boston.

The study, released just days after publication of a similar report from Italian researchers, is by far the largest to establish such a link. Results from the Boston study have not been published in a medical journal, meaning they have not undergone independent review by scientists not involved in the research.

Notably, the researchers also found that certain cancers apparently conferred no reduced Alzheimer’s risk, including melanoma (a cancer of the skin), prostate, and colorectal cancers. Breast cancer was not studied because there were too few cases in the database the researchers analyzed of nearly 3.5 million veterans, 98 percent of them men, who received care between 1996 and 2011.

The scientists said the reduced risk of Alzheimer’s was not simply because cancer patients die young, before they can develop the dementia.

“We went into this with doubt ourselves, and this has been a roadblock for people taking this research seriously, because people think if you are a cancer survivor you are going to die anyway,” said Dr. Jane Driver, the study’s lead researcher, and a geriatrician at the VA Boston Healthcare System.

Driver said that her team addressed that doubt by showing that cancer survivors lived long enough and even appeared to be at increased risk to develop other typical age-related diseases, including stroke, osteoarthritis, cataracts, and macular degeneration. And they found that most cancer survivors also had an increased risk for non-Alzheimer’s dementia.

The protective effect of most cancers seemed to extend only to Alzheimer’s.

“So if people were dying of cancer before they could get Alzheimer’s, we would have anticipated these alternative outcomes would be lower, too, but in fact they were higher,” said Dr. Laura Frain, a co-
researcher on the study and a geriatrician at the VA Boston Healthcare System.

But what surprised the team was the other finding: Cancer patients treated with chemotherapy enjoyed a reduced Alzheimer’s risk. They were 20 to 45 percent less likely to develop Alzheimer’s than cancer survivors who were not treated with chemotherapy.

The scientists are not sure why chemotherapy might be helpful, but plan to scrutinize the type of chemotherapy each patient received. Driver said a lot more work needs to be done but that perhaps some chemotherapies, at lower doses, might be useful in the battle against Alzheimer’s.

Maria Carrillo, the Alzheimer’s Association’s vice president of medical and scientific relations, said the apparent chemotherapy link is intriguing.

“What is [chemotherapy] doing to the brain cells that we can possibly mimic and target?” Carrillo said. “We think it’s time to pay attention to this as a possible treatment, because this was a very strong epidemiological study.”

The prevailing hypothesis in Alzheimer’s research is that amyloid, an abnormal protein found in Alzheimer’s patients, may be damaging brain cells and causing the cascade of changes that lead to dementia. Many researchers have been working on medications that clear amyloid from the brain, but that approach has shown little success in changing the course of the disease.

A growing number of scientists believe the drugs have been given too late, when irreversible damage has been done, and that the medications need to be given much earlier in the process.

Scientists at Brigham and Women’s Hospital’s Center for Alzheimer Research and Treatment have been working on amyloid studies, but Dr. Gad Marshall, associate medical director of the center, said the chemotherapy findings bear follow-up.

“Most people would be deterred by chemotherapy, in terms of it having pretty significant side effects,” he said. “But most people who have seen dementia first-hand, especially family members, would not be deterred by it, because it’s really a devastating condition.”

The findings are validation for Catherine Roe, an Alzheimer’s researcher at Washington University in St. Louis, who said she was laughed at in 2004 when she presented a small study showing an apparent link between cancer and a reduced Alzheimer’s risk at an international conference.

“People thought it was ridiculous,” Roe said. “One guy came up to me and said, ‘You are looking at the wrong disease, sweetheart.’ Now it looks like maybe we were really right.”

A study of more than 200,000 residents in Northern Italy published last week in the journal Neurology also found that cancer patients had a lower Alzheimer’s risk.

Roe noted in an editorial accompanying the study that similar relationships have been found between cancer and other diseases that destroy brain cells, such as Parkinson’s. And she said a protein known as pin1 may explain the inverse relationship between cancer and Alzheimer’s, because too much pin1 appears to make cells divide too rapidly, causing tumors, while not enough may lead to cell death, as seen in Alzheimer’s.

Scientists are now studying pin1 as a target for possible Alzheimer’s and cancer treatments.

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