Late Breaking News
Veterans' Study: Many Cancers, Chemotherapy Reduce Risk of Alzheimer's Disease
By Annette M. Boyle
BOSTON - A study involving more than three million veterans has found an intriguing inverse relationship between two dreaded diseases: cancer and Alzheimer’s disease (AD).
New research from the Boston VAMC suggests most cancers reduce the risk of developing the dementia by 12% to 51%, with chemotherapy further decreasing the risk. The study was presented recently at the Alzheimer’s Association International Conference. 1
“Our earlier research found about a 33% decreased risk of Alzheimer’s in people who had a history of any cancer. People diagnosed with Alzheimer’s had a 60% decreased risk of developing cancer,” said Jane A. Driver, MD, MPH, of the Boston VA geriatric division and assistant professor at Harvard Medical School, Cambridge, MA. That research was published in the British Medical Journal last year. 2
In the new study, the largest to analyze the relationship between AD and individual cancers, researchers studied the records of 3,499,378 veterans age 65 or older who were seen in the VA Healthcare System from 1997 to 2011. All were dementia-free at baseline. Participants had a mean age of 71, and 98% were male. The follow-up time was 5.65 years.
During the course of the study, 82,029 veterans developed AD. Of those, 24% had a history of cancer, while 76% did not. Of the study participants, 771,285 had a diagnosis of cancer before or during the study.
Researchers looked at the association of 19 types of cancer with AD and found that a history of most types of cancer significantly reduced the risk of developing AD. Cancers of the liver and pancreas were associated with the greatest risk reduction (51% and 44%, respectively) followed by esophageal cancer (33%), myeloma (26%), lung cancer (25%) and leukemia (23%). Lymphoma and cancers of the head and neck, stomach, genitals, thyroid and kidneys appeared to reduce risk of AD by 12% to 22%.
Melanoma, sarcoma and cancers of the prostate had positive associations with AD, however, slightly increasing the risk, although the high screening rates might have skewed results. Colorectal and bladder cancer appeared to neither increase nor diminish risk.
Driver noted that survival bias did not account for the results, explaining, “We only had 10 years of data and we had to address whether the results were skewed because when people get lethal cancers, they don’t have a chance to develop Alzheimer’s.”
As part of the study, the researchers analyzed the association between cancer and other age-related conditions such as stroke, osteoarthritis, cataracts and macular degeneration and found a positive association across the board. Most cancers also had a positive association with other types of dementias.
“It’s hard to say one thing explains the inverse relationship between cancer and Alzheimer’s. Each cancer is really a separate disease,” Driver said, adding that “Alzheimer’s and cancer have significant similarities in their pathophysiology. They are characterized by inflammation, excessive growth signals to cells, DNA damage and oxidative stress, but the end results are different. The genes that regulate cell division and cell death are indicated in both diseases.”
In both cases, cells get the message to divide. “In cancer, the cells transform and continue to proliferate. It’s impossible, though, for mature neurons to divide. When they are prompted to divide by abnormal signals, the only possible outcome is apoptosis or cell death,” which is characteristic of Alzheimer’s, Driver said.
Two proteins in particular, p53 and Pin1, play key roles in the pathophysiology of both diseases. For Pin1, which plays a role in cell cycle control and protein folding, “if the protein level is too high, it causes cancer; if it’s too low, it seems to cause Alzheimer’s,” Driver told U.S. Medicine.
Screening might account for some of the positive association with several of those cancers.
Melanoma, prostate and colorectal cancers “are cancers for which we actively screen people, particularly in the VA system,” Driver said. “There may be a diagnostic bias. Maybe if you have a positive screen for one disease, you are more likely to be screened for another and have a lower threshold for picking up that disease than would occur otherwise. Many of these cancers detected through screening would not have developed clinically significant symptoms.”
The treatment regimen for cancer also affects AD risk. Chemotherapy lowered AD risk by 20% to 45% for all cancers except prostate, while radiation treatment did not decrease Alzheimer’s risk.
Looking at all the patients with a history of bladder cancer who received radiation only, for instance, does not show any reduced risk of AD, but patients who have had bladder cancer treated with chemotherapy decrease their risk of AD by 45%. In hematologic cancers, patients who received radiation have a 5% reduced risk of AD; for those who had chemotherapy, the risk declines by 22%. Lung cancer shows the greatest treatment-based difference: a hazard ratio of .98 for radiation versus .75 for chemotherapy.
“If cancer treatments are able to stop neurons from trying to divide, that could protect them from Alzheimer’s,” Driver said. In addition, she said, some common cancer drugs stabilize the microtubules in neurons that break down in AD, while others prevent tau from sticking to itself and even dissolve tau tangles, another characteristic of Alzheimer’s.
Driver noted that the research presented at AICC was not a clinical trial.
“This was an observational study taking advantage of a really large database to generate hypotheses about what role cancer might play in preventing or treating Alzheimer’s. In future research, we’ll be able to go into more detail and have information on the exact drugs that patients received,” she said.
1. Frain L, Swanson D, Betensky R, Cho K, Gagnon D, Kowall N, Ping Lu K, Gaziano JM, Driver J. A Reduced Risk of Alzheimer’s Disease Is Associated with the Majority of Cancers in a National Cohort of Veterans. AICC 2013. Proposal 38434. July 16, 2013.
2. Driver JA, Beiser A, Au R, Kreger BE, Splansky GL et al. Inverse association between cancer and Alzheimer’s disease: results from the Framingham Heart Study. BMJ 2102;344:e1442.