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316 AWHONN Lifelines Volume 7 Issue 4
Amajor study has confirmed
the value of potential markers
for identifying people with
Alzheimer’s disease. Scientists at the
National Institute of Mental Health
(NIMH) found that levels of two
key indicators in spinal fluid distin-
guished clinically diagnosed
Alzheimer’s patients from controls
with 89 to 92 percent efficiency.
This matches or exceeds current
clinical diagnostic methods, such as
doctor’s evaluation of medical histo-
ry, cognitive testing, and brain
scans. However, the potential telltale
signs, or biomarkers, won’t be ready
for use as predictive and diagnostic
tools until completion of long-term
studies now under way. The findings
appear in the April 23, 2003, edition
of the Journal of the American
Medical Association.
“We’re hopeful that biomarkers
will eventually be developed to help
detect incipient illness in younger
people who are at risk but who may
not yet show any symptoms,” said
researchers. “Clues from biochemi-
cal, genetic and brain imaging stud-
ies could point to new possibilities
for preventive interventions.”
The NIMH study examined cere-
brospinal fluid (CSF) levels of two
protein fragments, hallmarks of the
disease process, found in brains of
Alzheimer’s victims: beta-amyloid,
which clumps together to form
brain-damaging plaques, and tau,
which strangles neurons in tangled
filaments. Like many previous stud-
ies, it found that CSF beta amyloid
levels drop, while tau levels rise in
Alzheimer’s. What’s new is that the
confidence level in this finding has
now been boosted by applying a
meta-analysis of the world literature
and adding “the largest cohort of
Alzheimer’s disease patients and
controls evaluated to date,” say the
researchers.
To gather their data, researchers
performed spinal taps on 131
Alzheimer’s patients and 72 control
subjects and measured CSF levels of
the suspect protein fragments. As
the fluid that bathes the brain, CSF
has long been considered the most
reliable window available into a liv-
ing human’s neurochemical activity.
Beta-amyloid levels in Alzheimer’s
patients averaged only 183
picograms per milliliter of CSF,
compared to 491 in controls.
Patients’ tau levels dwarfed controls
587 to 224 picograms per milliliter.
These differences remained signifi-
cant even after statistical analysis
controlled for effects of age and sex.
Taken together the two markers dis-
tinguished clinically diagnosed
Alzheimer’s patients from controls
with a sensitivity of 92 percent and
a specificity of 89 percent.
Years of education were associat-
ed with lower CSF tau levels among
Alzheimer’s patients, suggesting a
possible protective factor. Evidence
suggests that the changes in beta-
amyloid and tau levels may be pres-
ent early in the disease
process.
The researchers also
performed a meta-
analysis of 51 similar
studies, totaling 3,133
Alzheimer’s patients
and 1,481 control
patients. These included
17 controlled studies of
beta-amyloid winnowed
from 188 articles, and
34 studies of tau, sifted
from an initial list of
200 articles. Of the
beta-amyloid studies,
14 of the 17 found the
same pattern seen in the NIMH
sample. All of the tau studies
showed the same pattern as the
NIMH sample.
However, for both measures, the
researchers found considerable
overlap in levels between the
Alzheimer’s and control groups. “It’s
evident that the diagnostic sensitivi-
ty and specificity of these individual
CSF beta-amyloid and tau assays is
simply not sufficient to warrant
general clinical use of these bio-
markers for individual use,” they
caution. They call for additional
studies to standardize assay method-
ology, and for “real world” compar-
isons between Alzheimer’s patients
and people with other forms of
dementia, noting that these would
likely show even more overlap.
“Perhaps the most important
future use for such biomarkers is in
the prospective study of people at
risk for developing Alzheimer’s dis-
ease,” researchers noted. “By estab-
lishing a person’s baseline and
tracking levels over time, we might
be able to interpret gradual changes
as a sign that he or she is developing
the disorder.”
Potential Screening Tool For Alzheimer’s Disease
cer by the Food and Drug
Administration (FDA) in 1998, after
NCI released the results of the Breast
Cancer Prevention Trial (BCPT), a six-
year study of the drug. In BCPT,
tamoxifen was found to reduce the
incidence of breast cancer by 49 per-
cent. Based on that study, FDA
approved the drug for women at high
risk of developing invasive breast can-
cer. High risk was defined as women
age 35 and older who have a five-year
risk of at least 1.67 percent.
Using data on cancer risk factors
from the 2000 National Health
Interview Survey, researchers calculat-
ed the number of women in this
country eligible to take tamoxifen
based on FDA-approved indications.
They also projected the number of
white and black women who would
most likely have a net positive benefit
from taking the drug based on a bene-
fit-risk analysis. Because accurate data
on the frequency of adverse tamoxifen
effects in Hispanic women were not
available, estimates of how many
Hispanic women would likely benefit
from the drug could not be calculated,
they said.
The researchers estimated that 15.5
percent of women 35 to 79 years old in
this country, or about 10 million,
would be eligible to take tamoxifen
based on breast cancer risk alone.
When analyzed by race, 18.7 per-
cent of white women ages 35 to 79 in
the U.S., or 9.4 million, would be eli-
gible for tamoxifen, but only 4.9 per-
cent, or 2.4 million, are likely to ben-
efit from the drug. About 6 percent
of U.S. black women in the same age
range, or 430,000, would have a high
enough risk to take the drug, but
only 0.6 percent, or 43,000, would
likely derive a net benefit from it.
The rates are lower for black women
than white women, they said, because
the overall risk for breast cancer in
black women is lower and because the
rates of stroke, deep vein thrombosis
and pulmonary embolism are higher
than among white women. The results
for black women, however, are less sta-
ble than those for white women
because less is known about breast
cancer risk and the incidence of some
of the side effects in this group, said
Freedman.
In examining who would do well
on tamoxifen, the researchers found
that an overall net positive benefit was
related to age. Younger women are less
likely than older women to experience
the drug’s adverse affects. This means
that if a 40-year-old woman and a 60-
year-old woman had the same breast
cancer risk, the younger woman would
likely derive a better overall benefit
from the drug.
When the researchers did the age
analysis, they found the highest per-
centage of women likely to benefit
overall from tamoxifen were age 40 to
59. More than 8 percent of these
women would potentially gain from
chemoprevention, compared to 2.1
percent for women age 60 to 69.
In terms of preventing actual breast
cancers, the researchers estimated that
among the 2.4 million white women
who could likely benefit overall from
taking tamoxifen, 58,148 breast can-
cers would develop over the next five
years. But, if all these women took the
drug for that length of time and expe-
rienced the typical 49 percent reduc-
tion in breast cancer, 28,492 cases
could be prevented or deferred.
Further information on the risks
and benefits of taking tamoxifen for
breast cancer chemoprevention can be
obtained at NCI’s Web site http://cancer.
gov/bcrisktool.
All-In-One LifestyleChanges Lowers Blood Pressure
Lifestyle changes to prevent or
control high blood pressure need
not be made one at a time. But,
according to a study supported by the
National Heart, Lung, and Blood
Institute (NHLBI), with special
counseling, Americans can make all
the needed changes at the same time.
The best results were achieved when
the lifestyle changes included adoption
of the DASH diet, which is rich in
fruits, vegetables and lowfat dairy
products.
Results of the study, called PRE-
MIER, appear in the April 23, 2003,
issue of The Journal of the American
Medical Association.
“This is the first time a host of
behavioral steps to prevent or control
high blood pressure has been put
together in one intervention,” said
NHLBI Director Dr. Claude Lenfant.
“Past studies looked at one or two
changes at a time, and it was thought
that doing more would prove too hard.
But PREMIER shows that an all-in-
one approach works and can help
Americans reduce their blood pres-
sure, lowering their risk for heart dis-
ease and stroke.”
Recommended lifestyle steps to
prevent or control hypertension are to
• lose weight if overweight
• follow a heart-healthy eating plan,
which includes reducing salt and
other forms of sodium
• increase physical activity
• limit consumption of alcoholic
beverages
• quit smoking
Additionally, results of earlier studies,
published in December 2001 and April
1997, showed that the DASH diet sig-
nificantly lowers blood pressure, espe-
cially when combined with reduced
sodium intake. DASH stands for
“Dietary Approaches to Stop
Hypertension.”
PREMIER dealt with all of the
hypertension prevention and con-
trol steps. The study began in 1998
and was conducted at four clinical
August | September 2003 AWHONN Lifelines 317
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