Older persons with cancer have a reduced risk for Alzheimer's disease (AD), and people with AD have a reduced risk for cancer, a new study shows.
This inverse relationship between cancer and AD has been reported before, but the current study, conducted in Italy, has more patients and addresses some of the possible bias of previous research.
"I think we can say now with some certainty that Alzheimer's and cancer are intertwined in some way. Until now, research into Alzheimer's and cancer has been conducted completely separately. Our research suggests that they may be able to join forces to move both fields forward as there are common mechanisms at play," lead author Massimo Musicco, MD, National Research Council of Italy, told Medscape Medical News.
The study was published online July 10 in Neurology.
Second Disease Often Goes Undiagnosed
For the study, Dr. Musicco and colleagues examined the incidence of cancer and AD in people over 60 years of age living in the local health authority covering the northwest area of Milan between 2004 and 2009.
Cancer incidence was derived from a tumor registry and AD incidence from registries of drug prescriptions, hospitalizations, and payment exemptions.
Of the 204,468 residents considered, 21,451 newly diagnosed cancer cases and 2832 AD cases were found, giving a crude incidence rate per 10,000 person-years of 175.1 and 22.1, respectively. Only 161 individuals were found to have both diseases.
The researchers calculated the expected number of cancers in the patients with AD if it was the same as the general population but found that the number of cancer cases in the AD group was actually 35% less than in the general population. And similarly, the number diagnosed with AD was 50% lower in the cancer cohort than in the general population.
Cancer Cases in AD Cohort
| Number Observed | Number Expected | Relative Risk (95% Confidence Interval) |
| 161 | 281 | 0.57 (0.49 - 0.67) |
AD Cases in Cancer Cohort
| Number Observed | Number Expected | Relative Risk (95% Confidence Interval) |
| 161 | 246 | 0.65 (0.56 - 0.76) |
This relationship was observed in almost all subgroup analyses, suggesting that some anticipated potential confounding factors did not significantly influence the results.
Dr. Musicco noted that in previous studies, a second disease could have been under-represented once a first condition was diagnosed. For example, memory loss that is actually AD may be attributed to the cancer or chemotherapy and thus not diagnosed.
"So we looked at the incidence of the second diseases before and after the diagnosis of the first disease. If there was a bias there it should be just confined to the period after the diagnosis of the first disease, but actually we saw the same risk reduction in the second disease both before and after diagnosis of the first disease. So these concerns have been dealt with."
Commenting on a potential mechanism, Dr. Musicco said it's complicated but added that "cancer and Alzheimer's can be regarded as the opposite faces of senescence — the negative phenomena of aging. How cells age is controlled by many different genes.
"Certain genes that repair damaged tissues and cause cell proliferation in a beneficial way when we are young may also favor growth of cancer later in life. Other genes cause exactly the opposite effect — bringing about senescence of cells and apoptosis. These are linked to Alzheimer's disease and other neurodegenerative conditions," he added.
"So cancer and Alzheimer's may be viewed as 2 exactly antagonistic concepts. One is about cell proliferation and growth and the other is about cell aging and death. Genes that cause cancer to grow could well have a beneficial effect in degenerative disease. And vice versa. I would say each individual's genetics are programmed to be at a certain position on this spectrum."
The researchers would next like to conduct a study of more in-depth genetics of people with cancer and those with AD to shed more light on the mechanisms involved, which they say could provide insights into potential new treatment targets.
Growing Evidence Base
In an accompanying editorial, Catherine M. Roe, PhD, Washington University Knight Alzheimer’s Disease Research Center, St. Louis, Missouri, and Maria I. Behrens, PhD, MD, Hospital Clínico Universidad de Chile, Santiago, say that this latest study adds to the growing evidence suggesting an inverse relationship between the development of AD and cancer.
"Alterations in the activity of key molecules involved in survival pathways related to the decision to repair encountered damage and survive, or to proceed toward death by apoptosis, may explain a tendency to either develop a tumor or a neurodegenerative disorder such as AD," they write.
They give an example as the tumor suppressor p53, which is normally in charge of monitoring DNA damage but is inactivated in around 50% of cancers, therefore allowing abnormal cell proliferation. On the other hand, there is evidence of elevated levels of p53 in the brains of patients diagnosed with AD and several other neurodegenerative disorders, such as Huntington disease, amyotrophic lateral sclerosis, and Parkinson disease.
They conclude that regardless of the particular mechanism, "If future research confirms that the development of cancer and AD are inversely associated, this knowledge may help in gaining a better understanding of and developing new treatments for both diseases."
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