Survive Cancer, Lessen Alzheimer's Risk

Allison Shelley

March 20, 2012

March 20, 2012 — A new analysis of data from the Framingham Heart Study suggests that cancer survivors may have a reduced risk of Alzheimer's disease.

Investigators found that survivors of any cancer had a 33% lower risk of Alzheimer's disease and survivors of smoking-related cancers had a 74% decreased risk — neither explained by survival bias.

"An epidemiologic association between cancer and neurodegeneration is intriguing because these 2 families of diseases share many biological connections," lead investigator Jane Driver, MD, from Brigham and Women's Hospital in Boston, Massachusetts, told Medscape Medical News.

Dr. Jane Driver

"While cancer is a disease of inappropriate cell growth, neurodegeneration is characterized by inappropriate cell death. Genes that have a role in the cell cycle and apoptotic pathways are associated with both conditions," she said.

The results, published online March 12 in the British Medical Journal, were first presented in Hawaii at the American Academy of Neurology (AAN) 63rd Annual Meeting.

"The take-home message of our work is not that neurologists should be telling patients with Alzheimer's disease that they have less risk of cancer, but rather that a deeper understanding of the inverse relationship between cancer and Alzheimer's disease may someday lead to new therapies," Dr. Driver explained." Our findings support the growing evidence that people who are predisposed to cancer may be at decreased risk of neurodegeneration."

Evidence that patients with Parkinson's disease have a decreased risk of most cancers was first documented in the 1950s and researchers say the epidemiologic evidence is now convincing.

In this community-based prospective case-control study, investigators evaluated 1278 people with and without a history of cancer. Participants were aged 65 years or older with no dementia at baseline.

Over a mean follow-up of 10 years, investigators identified 221 cases of Alzheimer's disease. They found that survivors of any cancer had a reduced risk of Alzheimer's disease and survivors of smoking-related cancers had an even lower risk.

Table. Risk of Alzheimer's Disease

Survivors Hazard Ratio 95% Confidence Interval
Any cancer 0.67 0.47 - 0.97
Smoking-related cancers 0.26 0.08 - 0.82
Non–smoking-related cancers 0.82 0.57 - 1.19

In contrast to their decreased risk of Alzheimer's disease, survivors of smoking-related cancers had a substantially increased risk for stroke with a hazard ratio of 2.18 and 95% confidence interval of 1.29 to 3.68.

In a nested case-control analysis, participants with probable Alzheimer's disease had a lower risk of subsequent cancer with a hazard ratio of 0.39 and 95% confidence interval of 0.26 to 0.58 than reference participants. This was also the case for patients with any Alzheimer's disease (0.38) and any dementia (0.44).

The results match those of the 2 other available prospective studies. In a longitudinal memory cohort of 594 patients, those with cancer at baseline seemed to develop Alzheimer's disease at a lower rate than those with no history of cancer ( Neurology. 2005;64:895-898). The hazard ratio was 0.40 with a 95% confidence interval of 0.12 to 1.13.

In an analysis of 3020 people from the cognition cohort of the Cardiovascular Health Study, a history of cancer at baseline conferred a lower risk of probable Alzheimer's disease ( Neurology. 2010;74:106-112). The hazard ratio was 0.57 with a 95% confidence interval of 0.36 to 0.90.

These 2 families of diseases share many biological connections.

"Similar to their results," the authors write, "we found that the inverse relation became stronger as we excluded non-Alzheimer's and mixed dementias. Our risk estimates for incidence of cancer among those with and without Alzheimer's disease were essentially the same."

In an accompanying editorial, Mary Ganguli, MD, from the University of Pittsburgh School of Medicine in Pennsylvania said, "This report of an apparent mutually protective relation between Alzheimer's disease and cancer is intriguing, although not unprecedented. Others have previously hinted at such a link and a similar pattern has been described for cancer and Parkinson's disease."

It is hard to imagine a better population "laboratory" than the Framingham Study, Dr. Ganguli noted, which closely evaluates and monitors a large community-based cohort over time, minimizing selection and recall bias. "However, all potential biases and confounding effects cannot be accounted for in an observational study," she added.

"We will never know if people who died early of cancer were at the same risk of Alzheimer's disease as those who survived, as was pointed out in the excellent editorial that accompanied our article," Dr. Driver said. "This limitation can only be addressed when we have accurate biomarkers for both diseases that could be measured in prospective cohorts such as the Framingham Heart Study."

This study was funded by a National Heart, Lung, and Blood Institute contract and grants from the National Institute of Aging and National Institute of Neurological Disorders and Stroke. The investigators and editorialist have disclosed no other relevant financial relationships.

BMJ. Published online March 12, 2012. Abstract Editorial


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