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