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Mixed Dementia
Protecting Your Heart May Also Protect Your Brain
from Dementia
Having Alzheimers and vascular dementia is called
Mixed Dementia and strikes many seniors
Jan. 3, 2005 - Can the same actions that help
prevent a heart attack or stroke also prevent or slow the memory loss,
confusion and thinking problems of dementia? A new study suggests that
for many people, primarily senior citizens, the answer could be yes.
And for some, the impact of steps like controlling
blood pressure and cholesterol might be greater than the effect of
high-priced memory-preserving drugs.
Doctors now think that many people with symptoms
attributed solely to Alzheimer's memory loss, confusion, wandering,
trouble following instructions may in fact have mixed dementia.
Mixed dementia is a combination of
Alzheimer's disease and vascular
dementia, caused in part by problems with blood flow in the brain. It
may affect as many as 20 percent of the 6.8 million Americans with
dementia. It is particularly common in older patients, who often have
memory problems due to several conditions at once.
In the December 15 issue of the
Journal of the American Medical
Association, researchers from the
University of Michigan Health System, the
VA Ann Arbor Healthcare System
and the
Group Health Cooperative Center for Health
Studies in Seattle present a comprehensive review of what's
known and what's not about a condition called mixed dementia.
Having risk factors like high blood pressure and
high cholesterol does damage to small blood vessels in the brain and can
cause death of brain cells over time, says lead author Kenneth Langa,
M.D., Ph.D. In addition, the Alzheimer's disease process itself can
affect the walls of blood vessels in the brain, making strokes more
likely. Strokes can cause dementia through the death of large areas of
brain tissue, or through the build-up of damage from multiple small
strokes cased by athero-sclerosis in small arteries in the brain or the
larger carotid arteries in the neck.
In other words, processes that hurt the
cardiovascular system also hurt the brain, and inflict a further toll on
those with Alzheimer's disease.
For the new paper, the researchers reviewed all
recent medical studies on mixed dementia, vascular dementia and
Alzheimer's. They analyzed hundreds of articles, noting any results from
drug studies that were relevant to mixed dementia.
The review shows that drugs designed to slow the
progression of Alzheimer's disease have about the same effect in people
with mixed dementia as in people with Alzheimer's alone. That is, in
some people they cause a measurable but not dramatic improvement on
tests of cognitive function or other measures, or slightly slow an
inevitable decline. The authors looked at drugs like galantamine
(Reminyl), rivastigmine (Exelon), donepezil (Aricept) and memantine
(Namenda).
But when the authors reviewed the evidence relating
to heart-protecting therapy and dementia, they found significant
benefits. They conclude that efforts to treat cardiovascular risk
factors, especially high blood pressure, may be more effective than
memory drugs in protecting brain function.
Still, the authors note that more studies are
needed to give doctors a full picture of mixed dementia, and to show
them what works, and what doesn't, in preventing and slowing it.
Until those studies are completed, physicians
should talk with each patient or family individually about the treatment
route to pursue, says Langa. That discussion, in all patients with
dementia that might have a cardiovascular component, should include
advice about lifestyle changes and treatments to address risk factors
such as high blood pressure, high cholesterol, diabetes and physical
inactivity. In patients with heart rhythm problems, blocked neck
arteries or clotting disorders that can greatly increase the risk of
stroke, further treatment may be needed.
If a decision is made to prescribe one of the new
Alzheimer's drugs, the authors recommend that doctors follow up with
patients or their families in two to three months, to see if there has
been any improvement in memory or behavior, or whether the patient's
cognitive decline has slowed. A discussion of costs and benefits,
because of the high monthly cost of the drugs, is also advised.
Langa says that the review's findings have changed
the way he handles his patients with dementia and cardiovascular risk
factors, in the primary care clinic of the VA Ann Arbor Healthcare
System. He is also an assistant professor of general medicine at the
U-M Medical School, a research
investigator at the Ann Arbor VA, and a faculty associate at the
U-M Institute for Social Research.
The new review focuses on findings from randomized
controlled drug trials, and observational studies based on trends among
specific populations. Taken together, the analysis suggests that the
cardiovascular system may have a lot more to do with mental function
than many people realize. Paying attention to cardiovascular risk
factors could prevent some dementia and decrease the added burden of
strokes in those with Alzheimer's disease.
For example, one study that the authors reviewed
showed a 50 percent reduction in the incidence of dementia in a group of
patients with high blood pressure who were treated over four years with
a calcium-channel blocking blood pressure drug. And patients who
received the blood pressure drug had a lower chance of developing
Alzheimer's disease, vascular dementia or mixed dementia.
This corresponds with observational data showing
that people with high blood pressure are more likely to develop
cognitive impairment, a mild form of dementia that often acts as a
warning sign for later dementia. And other observational studies have
suggested that treatment for high blood pressure can protect against
cognitive decline.
The authors also looked at evidence relating to
drugs that reduce cholesterol or thin the blood. To date, they find,
prospective studies on cholesterol drugs called statins haven't shown a
specific effect on dementia, but follow-up periods in such studies have
been short.
There's other evidence that reducing cholesterol
may help brain function, though. Some, but not all, observational
studies have shown that people with high cholesterol in middle age are
more likely to develop mild cognitive impairment and Alzheimer's
disease. And since statins decrease risk of stroke, they can also
decrease the risk of harm to thinking ability that often comes with
stroke.
A recent study led by the new paper's senior
author, Eric Larson, M.D., MPH, of the Group Health Cooperative, notes
that people who have a certain genetic characteristic that puts them at
higher risk for both heart disease and dementia may get more cognitive
benefit than others from statin therapy. In an observational study, his
team found that people with a specific genetic variation that alters
production of a protein called APOE received more cognitive benefit from
statins than others.
Aspirin therapy to thin the blood and reduce
clotting, is another widespread heart-protecting measure. The authors
found several studies that attempted to assess the effect of aspirin on
vascular dementia. While an observational study in Sweden showed an
association between aspirin use and a decreased risk of dementia, there
are no data yet available from randomized controlled trials (the gold
standard of clinical research) that included aspirin for vascular
dementia.
Also uncertain, the authors found, was evidence on
the effect of complementary therapies vitamin E and ginkgo biloba, both
often touted as helping memory. More studies will be needed to assess if
these compounds have any effect on mixed dementia.
In all, says Langa, evidence is building that mixed
dementia can be prevented or slowed by addressing both factors that
cause it: the Alzheimer's disease process and the acute or chronic
reduction of blood flow to the brain.
The two are intertwined, he says, noting animal
research data showing that amyloid protein, the chief sign of
Alzheimer's disease, can infiltrate the walls of brain blood vessels and
increase the risk of small bleeding strokes. And other evidence suggests
that an under-supply of blood to the brain can stress brain cells and
perhaps jump-start the Alzheimer's disease process. Chronically high
blood pressure also impacts the brain's auto-regulation system for its
own blood supply.
Mixed dementia will continue to grow in importance
as our society ages and deals with the cardiovascular effects of our
current obesity and diabetes epidemics, he says. We need to help those
who have it now, and gather the data that will help us take steps to
prevent it in the future.
In addition to Langa and Larson, the study was
co-authored by Norman Foster, M.D., a professor of neurology at U-M who
directs the Cognitive Disorders Clinic and is helping to lead a new
national study that aims to find more biomarkers, in addition to APOE,
that might affect dementia risk and treatment response. Langa,
meanwhile, hopes to use ISR data to look at the relationship between
cardiovascular risk and dementia in an ongoing national study of older
Americans.
The study was funded by the
National Institute on Aging, the
Alzheimer's Association, the Hartford Foundation and the Paul
Beeson Physician Faculty Scholar program.
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