Alzheimer's, Dementia & Mental Health
Lower Risk of Alzheimer’s Linked to Cancer, Later
Retirement, Diabetes Med, Better Economic Status
Studies presented at Alzheimer’s Association
conference point to unusual links to reducing your risk of this dementia
July 17, 2013 – Research presented at a meeting of
Alzheimer’s disease experts revealed some surprising things that reduce
the risk of this cause for cognitive decline. Most cancers, for example,
are associated with a significantly lowered risk of Alzheimer’s and the
risk drops even more if the cancer is treated with chemotherapy. A more
controllable way to avoid AD is to retire later in life. And, if
treating type 2 diabetes, take the medication Metformin. It also appears
to help if you are higher on the socioeconomic scale.
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 at the Alzheimer’s Association
International Conference 2013 in Boston. This study also 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
“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
“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
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 santé
et de la recherché médicale) 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
“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. Françoise 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
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.”
Results of Cancer
82,028 veterans were diagnosed with AD during a
median follow-up of 5.65 years. AD was less frequent in veterans with a
history of cancer (24 percent) than without (76 percent). The majority
of cancers had an inverse relationship with AD.
The lower risk was greatest among survivors of lung
(HR 0.75, 95 percent CI 0.69-0.81), leukemia (HR 0.77, 95 percent CI
0.68-0.87), myeloma (HR 0.73, 95 percent CI 0.60-0.90), esophageal (HR
0.66, 95 percent CI 0.51-0.86), pancreas (HR 0.56, 95 percent CI
0.39-0.80), and liver (HR 0.49, 95 percent CI 0.31-0.75) cancer. Notable
exceptions included prostate cancer (HR 1.12, 95 percent CI 1.09 -1.15)
and melanoma (HR 1.14, 95 percent CI 1.05-1.25).
In contrast, all cancers were associated with a
substantially increased risk of stroke when we used this as an
alternative outcome (HR 1.27-1.70). Regardless of cancer type, receiving
chemotherapy and/or radiation substantially reduced AD risk by 17-23
percent. In the subset of patients with cancer, chemotherapy but not
radiation conferred a lower risk of AD (HR 0.55-0.80) for all cancers
Conclusions: We found that the majority of cancers
have an inverse relationship with AD even after adjustment for
treatment. Reception of chemotherapy was associated with a reduced risk
for subsequent AD in nearly all cancers. These findings were not
primarily due to mortality bias. Additional research is needed to
determine if these findings have therapeutic implications for AD.
History of Cancer and Risk of Subsequent AD
HR and 95% CI for AD*
Any cancer (n=771,285)
Head + neck (n=40,837)
Head + neck (n=40,837)
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