Cancer And Chemotherapy Linked With Decreased Risk Of Alzheimer's Disease In Veterans

-- Three other studies reported at AAIC 2013 illuminate Alzheimer's risk factors, point to potential new strategies for treatment, prevention

BOSTON, July 15, 2013 /PRNewswire/ -- Most kinds of cancer are associated with a significantly decreased risk of Alzheimer's disease, according to a study of 3.5 million veterans reported today at the Alzheimer's Association International Conference® 2013 (AAIC® 2013) in Boston. In addition, the study suggested that chemotherapy treatment for almost all of those cancers conferred an additional decrease in Alzheimer's risk.

Three other researchers presented results of epidemiologic studies that uncovered risk factors and/or possible therapies for Alzheimer's disease. The results indicated that:

• Metformin, a medication for type 2 diabetes, may be linked with lower Alzheimer's risk among type 2 diabetes patients compared with other therapies.
• Older age at retirement appears to be associated with reduced Alzheimer's risk.
• Socioeconomic disparities may account for the previously observed increased risk of Alzheimer's among African Americans.

"With these large-cohort studies and others, we are beginning to see the outlines of a broad picture of Alzheimer's disease risk and prevention factors," said Maria Carrillo, Ph.D., vice president of medical and scientific relations at the Alzheimer's Association.

"However, we need to know even more about what specific factors actually raise and lower risk for cognitive decline and Alzheimer's. To do that, we need longer-term studies in larger and more diverse populations, and more research funding is required to make that happen. Alzheimer's research would benefit from its own version of the Framingham Study, which has taught us so very much about preventable risk factors for heart disease and stroke," Carrillo said.

"With funding of research being a critical need for progress, the National Plan to Address Alzheimer's Disease must be fully implemented and the $100 million identified for Alzheimer's and dementia research this fiscal year needs to be funded," Carrillo concluded.

Cancer history and chemotherapy are associated with decreased risk of Alzheimer's

A growing body of evidence suggests a possible association of cancer with reduced risk for Alzheimer's disease; until now, whether the association differs between cancer types or is modified by cancer treatment is unknown.

Laura Frain, M.D., a geriatrician at VA Boston Healthcare System, and colleagues analyzed the health records of 3,499,378 veterans age 65 and older who were seen in the VA health care system between 1996 and 2011 and who were free of dementia at baseline. The objective was to evaluate the relationship between a history of 19 different cancers, cancer treatment and subsequent Alzheimer's disease.

Over a median follow-up of 5.65 years, 82,028 veterans were diagnosed with Alzheimer's. Twenty-four (24) percent of those veterans with Alzheimer's had a history of cancer, while 76 percent did not.

The researchers found that most types of cancer were associated with reduced Alzheimer's risk, ranging from 9 percent to 51 percent. Reduced risk was greatest among survivors of liver cancer (51 percent lower risk), cancer of the pancreas (44 percent), cancer of the esophagus (33 percent), myeloma (26 percent), lung cancer (25 percent) and leukemia (23 percent). Cancers that did not confer a reduced Alzheimer's risk, or were associated with an increased risk, included melanoma, prostate and colorectal cancers.

The researchers found no association between cancer history and reduced risk of any other typical age-related health outcome; in fact, cancer was associated with an increased risk of stroke, osteoarthritis, cataracts and macular degeneration. Most cancer survivors were also at increased risk for non-Alzheimer's dementia.

"Together, these findings indicate that the protective relationship between most cancers and Alzheimer's disease is not simply explained by increased mortality among cancer patients," said Frain. "More research is needed to determine if these results have therapeutic implications for Alzheimer's."

Among veterans with a cancer history, treatment with chemotherapy but not radiation reduced Alzheimer's risk by 20 to 45 percent, depending on cancer type, with the exception of prostate cancer.

"The potential protective effect of chemotherapy is supported by recent experimental studies," Frain observed. "The results of this study are interesting because they could help focus future research onto the specific pathways and treatment agents involved in the individual cancers that are associated with a reduced risk of Alzheimer's. This could potentially open new therapeutic strategies for Alzheimer's prevention and treatment."

Metformin is linked with lower dementia risk than other type 2 diabetes therapies

Type 2 diabetes doubles the risk of dementia. However, until recently, little research has been done to examine the association between type 2 diabetes treatments and dementia risk. Rachel Whitmer, Ph.D., and colleagues at Kaiser Permanente Division of Research studied a cohort of 14,891 type 2 diabetes patients age 55 and older who began diabetes therapy between October 1999 and November 2001. Only patients who started a single therapy (metformin, sulfonylureas, thiazolidinediones (TZDs) or insulin) were included. The patients were followed for up to five years.

Patients initiating metformin, an insulin sensitizer, had a significantly reduced risk of developing dementia compared with patients on other diabetes therapies. Compared with those taking sulfonylureas, those initiating metformin had a 20 percent reduced risk of dementia, while those initiating TZD or insulin had no difference in risk.

"These results provide preliminary evidence that the benefits of insulin sensitizers may extend beyond glycemic control to neurocognitive health," said Whitmer. "Research in animals suggests that metformin may contribute to the creation of new brain cells and enhance spatial memory."

Trials are currently under way to evaluate metformin as a potential therapy for dementia and mild cognitive impairment, which is thought to be, in some cases, a precursor to Alzheimer's disease.

Older age at retirement is associated with reduced risk of dementia

Some research has suggested that intellectual stimulation and mental engagement throughout life may be protective against Alzheimer's disease and other dementias. In an analysis of health and insurance records of more than 429,000 self-employed workers in France, reported at AAIC 2013, Carole Dufouil, Ph.D., director of research in neuroepidemiology at INSERM (Institut National de la sante et de la recherche medicale) at the Bordeaux School of Public Health, and colleagues found that retirement at older age is associated with a reduced risk of dementia.

The researchers linked health and pension databases of self-employed workers who were living and retired as of December 31, 2010. Workers had been retired on average for more than 12 years. Prevalence of dementia in this group was 2.65 percent.

Analyses showed that the risk of being diagnosed with dementia was lower for each year of working longer (i.e., higher age at retirement) (hazard ratio of dementia was 0.968 (95 percent Confidence Interval = [0.962-0.973]). Even after excluding workers who had dementia diagnosed within the 5 years following retirement, the results remained unchanged and highly significant (p<0.0001).

"Our data show strong evidence of a significant decrease in the risk of developing dementia associated with older age at retirement, in line with the 'use it or lose it' hypothesis," said Dufouil. "The patterns were even stronger when we focused on more recent birth cohorts."

"Professional activity may be an important determinant of intellectual stimulation and mental engagement, which are thought to be potentially protective against dementia," observed Dufouil. "As countries around the world respond to the aging of their populations, our results highlight the importance of maintaining high levels of cognitive and social stimulation throughout work and retired life, and they emphasize the need for policies to help older individuals achieve cognitive and social engagement.

The study was also coordinated by the International Longevity Center-France (Head: Prof. Francoise Forette).

Socioeconomic disparities may explain higher Alzheimer's risk among African Americans

Alzheimer's disease and other dementias have been shown to be higher among older blacks in the United States than older whites; however, risk factors that might account for this difference have not been extensively studied.

Note: According to the Alzheimer's Association 2013 Alzheimer's Disease Facts and Figures report, older African-Americans are about twice as likely to have Alzheimer's and other dementias as older whites, and Hispanics are about one and one-half times as likely to have Alzheimer's and other dementias as older whites.

Kristine Yaffe, M.D., of the University of California, San Francisco and the San Francisco VA Medical Center, and colleagues sought to determine if differences in dementia rates by race existed among a cohort of community dwelling elders and whether any differences observed could be explained by socioeconomic status (SES) indicators (income, financial adequacy, education and literacy) and health-related factors.

The scientists evaluated dementia risk among 3,075 black and white elders (mean age 74.1 years) participating in the ongoing prospective Health, Aging and Body Composition Study who were free of dementia at baseline.

During 12 years of follow-up, 18.7 percent of participants were determined to have developed dementia, based on prescribed medications, hospital records and cognitive decline. In this population, African-Americans were 1.5 times more likely to develop dementia than whites (21.9 percent vs. 16.4 percent). However, after adjusting for socioeconomic factors including education level, literacy, income and financial adequacy, the researchers found that the difference in risk was no longer statistically significant.

"Our findings suggest that differences in socioeconomic factors may, in large part, explain racial and ethnic disparities in dementia rates," said Yaffe. "Future studies that investigate these disparities should take a broad range of socioeconomic factors into account."

Yaffe suggested that more studies are needed "to explore the potential benefits of improving socioeconomic risk factors as a way of reducing dementia rates."

(Disclosure: Dr. Yaffe is co-chair of the AAIC 2013 Program Committee.)

About AAIC
The Alzheimer's Association International Conference (AAIC) is the world's largest conference of its kind, bringing together researchers from around the world to report and discuss groundbreaking research and information on the cause, diagnosis, treatment and prevention of Alzheimer's disease and related disorders.  As a part of the Alzheimer's Association's research program, AAIC serves as a catalyst for generating new knowledge about dementia and fostering a vital, collegial research community.

About the Alzheimer's Association
The Alzheimer's Association is the world's leading voluntary health organization in Alzheimer care, support and research. Our mission is to eliminate Alzheimer's disease through the advancement of research; to provide and enhance care and support for all affected; and to reduce the risk of dementia through the promotion of brain health. Our vision is a world without Alzheimer's. Visit www.alz.org or call 800.272.3900.