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Alzheimer's, Dementia & Mental Health
Deepening Connections Between Diabetes and
Alzheimer’s Revealed
Existing diabetes
therapies may help fight Alzheimer’s
July 18, 2006 - There is a growing body of
scientific evidence that links diabetes with Alzheimer’s, and which may
enable already approved diabetes therapies to be quickly tested for
effectiveness against the deadly brain disease. New data from drug
trials and long-term population studies were reported this week in
Madrid at the 10th International Conference on Alzheimer's Disease and
Related Disorders (ICAD), presented by the Alzheimer’s Association.
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Alzheimer's, Dementia & Mental Health |
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“A connection between Alzheimer’s and diabetes has
major public health implications,” said Ronald Petersen, M.D., Ph.D.,
vice chair of the Alzheimer’s Association’s Medical & Scientific
Advisory Council.
“The number of people with Alzheimer’s, and the
number that will soon get it, is rising dramatically as the Baby Boomers
turn 60, which is approaching the age of highest risk. Will this growth
be redoubled by the rising tide of obesity and diabetes?”
Nearly one-third of American adults – perhaps as
many as 73 million people – have diabetes or higher than normal blood
sugar levels, according to a study from the National Institute of
Diabetes and Digestive and Kidney Diseases that was published in the
June 2006 issue of Diabetes Care.
“At the same time, drugs and other treatment
strategies – such as changes in diet and exercise – already developed
for diabetes may prove useful in Alzheimer’s, and, if so, then we’ll
have decades of diabetes research and real life experience to bring to
the effort to better treat and prevent Alzheimer’s,” Petersen said.
● Borderline diabetes linked with increased risk
of dementia and Alzheimer’s
Previous studies have consistently shown an association between
diabetes and dementia, and the adverse impact of early stage diabetes on
cognitive functions. Weili Xu, M.D., and colleagues from the Karolinska
Institutet and the Stockholm Gerontology Research Center, Sweden, sought
to examine the effects of borderline diabetes on the development of
dementia and Alzheimer’s.
For nine years, the investigators followed 1,173
individuals age 75 years and older who were free of dementia and
diabetes at baseline; borderline diabetes was identified in 47 subjects.
About one in three (397) of the subjects developed dementia during the
follow-up, including 307 subjects who developed Alzheimer’s.
After controlling for other major vascular factors,
borderline diabetes was associated with an almost 70 percent increased
risk of developing dementia and Alzheimer’s disease in this population.
Further analysis suggested that such a significant association was
present only among non-carriers of APOE e4 allele, a gene that increases
risk for the most common form of Alzheimer’s. The risk for Alzheimer’s
was especially high when borderline diabetes occurred with severe
systolic hypertension (=180 mm Hg).
“Our findings have significant implications for
public health because some studies show that impaired glucose regulation
can be improved by lifestyle changes,” Xu said. “Our findings also
highlight the need to detect borderline diabetes in order to proactively
address both type 2 diabetes and dementia.”
● Poor blood sugar control may dramatically
increase risk of dementia
Research suggests that people with type 2 diabetes have an increased
risk of dementia and Alzheimer’s disease. A study by Rachel A. Whitmer,
Ph.D., of Kaiser Permanente’s Division of Research, Oakland, Calif., and
colleagues suggests that among people with diabetes, those with very
poor blood sugar control are at the greatest risk.
The researchers studied 22,852 patients with type 2
diabetes for eight years to determine if elevated glycosylated
hemoglobin, a marker of blood sugar control, correlated with increased
risk of dementia. Participants were members of the Kaiser Permanente of
Northern California Diabetes Registry (66 percent Caucasian, 10 percent
African American, 11 percent Asian, 10 percent Latino, 3 percent
Native-American or other) age 50 and older.
Those with very poor blood sugar control were more
likely to develop dementia. Compared to those with normal glycosylated
hemoglobin levels (< 7), those with levels greater than 12 were 22
percent more likely to develop dementia, while those with levels greater
than 15 were 78 percent more likely to get dementia.
“Effective blood sugar control may lower risk of
another diabetes associated complication – dementia,” said Whitmer.
● Diabetes-related toxins may worsen memory
function
Sugar-related toxins known as advanced glycation end products (AGEs)
are increased in people with diabetes, as well as in persons with
cardiovascular and kidney disease – all are major chronic diseases of
aging. They also are present in the brains of people with Alzheimer’s.
Test tube studies show AGEs may contribute to the formation of
Alzheimer’s plaques and tangles.
AGEs are produced in the body and also are absorbed
from common foods processed at high temperatures. A piece of toasted
bread has higher AGEs than one that is not toasted. Similarly, broiling
a chicken produces more AGEs than boiling it.
Michal Schnaider Beeri, Ph.D., from the Mount Sinai
School of Medicine in New York City, and colleagues evaluated nearly 200
cognitively healthy people 70 years old or older with tests of memory
and thinking ability, and measured the AGE levels in their blood. They
found that people with the highest AGE levels did significantly worse on
six different tests than those with low AGE, and they tended to do worse
on four more tests. With the exception of age, there were no obvious
risk factors responsible for this relationship, including gender,
educational level, heart disease and related conditions such as high
blood pressure.
“Since we know that a diet low in AGEs decreases
AGE levels in the blood, these results raise the possibility of studying
dietary interventions designed to prevent or delay Alzheimer’s,” said
Beeri.
● Alzheimer’s may be forestalled by
thiazolidinediones
The thiazolidinediones (TZDs), including pioglitazone and
rosiglitazone, are used with diet and exercise to treat type 2 diabetes,
alone or in combination with other drugs. They lower blood sugar by
helping the cells of the body use insulin more efficiently to remove
excess sugar from the blood. It has been suggested that they also may
influence inflammation and other brain cell processes that may be
related to the development of Alzheimer's.
Donald R. Miller, Sc.D., from the Boston University
School of Public Health and the Center for Health Quality, Outcomes, and
Economic Research in Bedford, MA, with colleagues studied diabetes
patients treated with TZDs and other diabetes medications to evaluate if
TZD use was associated with fewer new cases of Alzheimer’s. Using data
from the U.S. Department of Veterans Affairs, the researchers identified
142,328 patients who received a first prescription for TZD or insulin
without prior prescriptions for either medication or a recorded
diagnosis of Alzheimer’s. Patient data was followed forward and
monitored for an Alzheimer’s diagnosis.
“We thought that if taking a TZD slows or prevents
the progression of Alzheimer’s or reduces the severity of Alzheimer’s
symptoms, it should delay the time when patients are first given a
diagnosis and, thus, should appear as lower incidence or fewer new
cases,” Miller explains.
The researchers found that those prescribed TZDs
had lower rates of Alzheimer’s. They estimated that the veterans taking
TZDs had almost 20 percent fewer new cases of Alzheimer’s than those
taking insulin. Similar results were found in a separate comparison
between TZD users and patients starting metformin, another drug used to
treat diabetes.
“These results are encouraging and suggest that
TZDs may provide important benefits beyond their use in treating
diabetes,” says Miller. “Our findings cannot be taken as conclusive.
This study must be confirmed by other epidemiologic research and
clinical trials.”
● Diabetes drug may also treat Alzheimer’s
disease
Pioglitazone is an FDA-approved medication for type 2 diabetes.
Preliminary studies indicated that pioglitazone could reduce
inflammatory reactions to the abnormal accumulations of amyloid beta
protein that occur in Alzheimer’s. Other research suggests that blood
sugar and insulin levels, which are regulated by pioglitazone, can also
influence memory and thinking in people with Alzheimer’s.
David S. Geldmacher, M.D., of the University of
Virginia, Charlottesville, along with colleagues at Case Western Reserve
University in Cleveland, Ohio, conducted a small, 18-month study of
pioglitazone’s effects in nondiabetics with Alzheimer’s to establish the
safety of long-term use in this population. Secondarily, they looked at
whether pioglitazone treatment might slow progression of the disease.
Twenty-five people (12 pioglitazone, 13 placebo) completed the study.
Pioglitazone had similar side effects in people
with Alzheimer’s as it does in people with diabetes – primarily foot and
ankle swelling. No serious or life-threatening side effects were
associated with the medication. The researchers found no statistically
significant differences in memory or thinking, daily function, or
abnormal behaviors between the pioglitazone and placebo groups. However,
there was a tendency for those taking pioglitazone to show less
worsening over time on some assessments.
“These preliminary results are promising enough to
carry out further studies of pioglitazone in larger groups of patients
with Alzheimer’s disease,” said Geldmacher.
● About ICAD
The 10th International Conference on Alzheimer's Disease and Related
Disorders (ICAD), presented by the Alzheimer's Association, is the
largest gathering of Alzheimer researchers in history. At ICAD 2006,
more than 5,000 researchers will share groundbreaking information and
resources on the cause, diagnosis, treatment and prevention of
Alzheimer’s and related disorders. As a part of the Association’s
research program, ICAD serves as a catalyst for generating new knowledge
about dementia and fostering a vital, collegial research community. ICAD
2006 will be held at IFEMA Feria de Madrid, Centro de Convenciones,
North Section - Hall 9 and 10, IFEMA Convention Center, Madrid, Spain.
About the Alzheimer’s Association
The Alzheimer’s Association, the nonprofit world leader in Alzheimer’s
research and support, is the first and largest U.S. voluntary health
organization dedicated to finding prevention methods, treatments and an
eventual cure for Alzheimer’s. For more than 25 years, the
donor-supported Alzheimer’s Association has provided reliable
information and care consultation; created supportive services for
families; increased funding for dementia research; and influenced public
policy changes. For more information, call (800) 272-3900 or visit
www.alz.org.
● Weili Xu – Borderline Diabetes
Mellitus and Risk of Dementia and Alzheimer Disease: A Population-Based
Longitudinal Study (Funders: Alzheimer’s Association, Gamla Tjänarinnor
Foundation, Swedish Research Council)
● Rachel A. Whitmer – Glycemic
Control and Risk of Dementia in a Cohort of Patients with Type 2
Diabetes (Funder: NIDDK/NIH)
● Michal Schnaider Beeri – Advanced
Glycation Is Associated with Cognitive Impairment in Very Old Women (Funder:
NIA/NIH)
● David S. Geldmacher – A
Double-Blind, Placebo-Controlled, 18-Month Pilot Study of the PPAR-Gamma
Agonist Pioglitazone in Alzheimer's Disease (Funders: Takeda
Pharmaceuticals North America, NIA/NIH)
● Donald R. Miller –
Thiazolidinedione Use May Forestall Progression of Alzheimer’s Disease
in Diabetes Patients (Funders: U.S. Department of Veterans Affairs,
GlaxoSmithKline Worldwide Epidemiology)
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