Children of parents with Alzheimer's disease can develop memory
problems in
their 50s or even younger - much earlier than previously thought -
according to a large study released Wednesday by researchers at
Boston
University School of Medicine.
The study subjects, who carried a gene strongly linked to
Alzheimer's,
performed worse in memory tests, on average, than other middle-aged
people
who had the same gene but did not have a parent diagnosed with
Alzheimer's.
The difference in memory between the two groups was equivalent to
approximately 15 years of brain aging, researchers found..
"How big an effect we saw was surprising," said Dr. Sudha
Seshadri, a BU
associate professor of neurology and senior author of the study.
"It was
like you were comparing two groups, 55-year-olds to 70-year-olds."
Researchers not involved with the study say the findings have
broad
implications because they are the first to demonstrate changes in
cognitive
abilities years before the age at which the degenerative brain
disease is
diagnosed. By the time the most common form of Alzheimer's is
confirmed,
usually around age 75, it has irreparably damaged large sections of
the
brain's memory center.
The BU findings do not suggest that everyone with the gene,
known as
APOE-e4, will develop Alzheimer's, said Seshadri. The gene is
believed to
play a role in about 50 percent of Alzheimer's cases. The study
also did
not address whether the people showing early memory impairment were
destined to develop Alzheimer's.
The memory of the affected group was diminished, but still
within a broad
range considered normal, researchers said. The deficits would not
be
noticeable to the average person, researchers said.
"These people are not having trouble at work," Seshadri said.
As scientists race to find Alzheimer's treatments, the latest
findings may
help researchers one day pinpoint when medical interventions should
be
started to halt the brain-ravaging process before it takes hold.
Alzheimer's afflicts roughly 5 million Americans and has no known
cure.
The BU study, which included 715 participants ages 37 to 80, has
been
accepted for presentation at the annual meeting in April of the
American
Academy of Neurology, the nation's premier organization of brain
specialists. However, the study has not yet gone through the
traditional
scientific vetting process, which includes other scientists
reviewing the
data before it is published in a journal.
The BU participants come from the Framingham Heart Study, which
has tracked
three generations. It started in 1948 to study cardiovascular risks
and
later expanded to include other diseases.
In the latest research on Alzheimer's, participants were
separated into
two groups. Participants in both groups carried the APOE-e4 gene,
but in
one group, participants also had at least one parent with
Alzheimer's or
dementia. The other group had parents who did not have the disease.
Both groups were given visual and verbal memory tests, in which
participants were shown complex images and also were told short
stories.
Twenty minutes later, they were asked to draw the figures and
recite the
stories as precisely as they could recall. The group with a
parental
history of Alzheimer's disease scored, on average, significantly
worse than
the one with no parental Alzheimer's.
Other research has shown that significant changes, such as the
buildup of
amyloid plaques in the brain, take place at least a decade before
Alzheimer's disease is diagnosed. But the BU study is the first to
demonstrate that measurable changes in memory may also be
happening.
"If that bears out, it appears that Alzheimer's starts years
before it's
diagnosed," said Dr. Randy Bateman, assistant professor of
neurology at
Washington University School of Medicine in St. Louis. Bateman is
conducting a separate, large-scale Alzheimer's study that is
measuring
brain fluid and plaques of middle-aged participants as well as
testing for
memory impairment.
Bateman said that if other studies replicate BU's findings, the
confirmation of very early symptoms could provide physicians with a
"window of opportunity" to treat patients before the brain is
severely
damaged. Currently there are a few approved medications to slow the
mental
decline from Alzheimer's, but they are given only after the disease
has
been diagnosed.
There is a genetic test to detect the APOE-e4 gene studied by
the BU
researchers, used by physicians to help diagnose Alzheimer's in
patients
who already are displaying symptoms. With scientists still
unraveling the
connections between APOE-e4 and Alzheimer's - some believe there
may be up
to a dozen more unidentified genes that play a role in the disease
- none
are recommending that healthy people seek such testing.
"I wonder about genetic discrimination," said Dr. Rudy Tanzi,
a neurology
professor at Harvard Medical School who co-discovered three other
genes
that have been linked to early-onset Alzheimer's, a more rare form
of the
disease that typically strikes before 65.
"If it's out there that my parents have APOE-e4, there is a
chance my
employer might know and wonder, 'Should I promote this guy?"'
Tanzi said.
The BU findings, he added, increase the urgency for stronger
genetic
nondiscrimination laws. Tanzi said that even though a federal law -
The
Genetic Information Nondiscrimination Act, enacted last year -
protects
against employment discrimination, he worries about subtle
discrimination
in the workplace.
"I am not sure how wise it is to have genetic information about
your
cognitive function when you don't have the disease," Tanzi said.
"People
risk discrimination for something they can't help."
Kay Lazar can be reached at klazar@globe.com.
c.2009 The Boston Globe