— Alzheimer’s disease is one of the conditions that
Americans are most afraid they will get, second only to
cancer. Yet at least a generation of focused research has gone
by without an effective treatment or sure advice on how to
of Pittsburgh Alzheimer’s researchers are among those
leading studies and while huge challenges still exist in
making progress, they see hope in recent reports.
research is examining both treatment and prevention, using the
latest technology of imaging a person’s brain. In addition
to the changes in the way a person thinks, Alzheimer’s is
associated with physical changes, including beta amyloid
plaque and tau protein "tangles" in the brain.
Lopez, a professor of neurology at Pitt and director of the
University of Pittsburgh Alzheimer’s Disease Research
Center, said he is concerned that, despite improved
technology, it will still take another 10 years to get useful
are a handful of studies, including the multisite A4 Study at
Pitt, that are examining people without any sign of Alzheimer’s
and following them for 10 years with brain scans. They hope
this will explain why one person develops the disease and
another doesn’t. Dr. Lopez is the principal investigator in
follow them as they are normal, for about four to five years;
then symptoms begin to appear and dementia is diagnosed. Then
we can understand these early scans and know how fast the
Lopez also oversees the Pittsburgh arm of the ongoing global,
multisite study known as ADNI. It is assessing information
collected from cognitive tests, imaging, genetics and amyloid
and tau biomarkers as patients are followed over several years
through normal aging to diagnoses of mild cognitive impairment
or dementia, including Alzheimer’s. This study will provide
information about the individuals who are more vulnerable to
develop Alzheimer’s disease.
people have amyloid processes but have no symptoms. Others
have no amyloid," Dr. Lopez said about questions
researchers have. "What makes a person vulnerable? It is
a chemical connection; does stiffness in the arteries
correspond to amyloid in the brain? We now know that
hypertension is connected to Alzheimer’s."
people go through aging takes time," Dr. Lopez said —
with all the technology (to aid research), there is still the
human factor ... you need to follow people through the aging
process. The whole process will take two generations."
meantime, National Institutes of Health funding for Alzheimer’s
research is not keeping up with the need, he said, and that is
discouraging young scientists. "We lost one generation of
researchers. That’s significant damage."
in particular, is costly, Dr. Lopez said. Armed with new
technology, recent studies point to malfunctioning tau as the
main cause of the decline in thinking and memory in Alzheimer’s,
not the buildup of beta amyloid fragments in the brain, which
has been the focus of research for more than 20 years.
news is that achievements are being made in therapies and
technology — and the public mindset is in the right place,
said William "Bill" Klunk, Pitt professor of
psychiatry and neurology, and co-director of the research
have reached the point where it’s worth the effort,"
said Dr. Klunk, also chair of the Alzheimer’s Association
Medical and Scientific Advisory Council, which guides the
direction of the group’s research program.
Alzheimer’s Association has worked hard with its
collaborators, to draw attention to the need for more funding,
and that has shown some success," he said, adding that
although more than $500 million for research was in this year’s
federal budget, an additional $300 million is requested for
association predicts that without a medical breakthrough, by
2050 there will be 13.8 million Americans over age 65 with the
disease. The likelihood of developing Alzheimer’s doubles
every five years after age 65. After age 85, the risk is
almost 50 percent.
not just amyloid or tau proteins, Dr. Klunk said. "In
older people, there is more incidence of the disease, there
are more pathologies in the brain, more protein deposits.
There are subtle blood flow changes. All of these things
change. It’s more likely that their Alzheimer’s disease is
a combination of more than one thing going on in the
are several trials at Pitt testing drugs to treat or prevent
Alzheimer’s. Trials now recruiting include the A4 Study,
which is testing a drug, given by IV infusion, that might
prevent or delay the onset of Alzheimer’s in people who may
be at risk, as seen in a brain imaging test known as a PET
scan. More information is available at a4study.org.
medications now are most frequently prescribed to treat the
symptoms of Alzheimer’s disease: Aricept, Razadyne, Exelon
can slow down the progression of the disease," Dr. Lopez
said. "The risk of going to a nursing home is diminished,
but they’re not magic."
addition, plasma exchange is being tested at Pitt as a
treatment of symptoms in patients with mild to moderate
Alzheimer’s. The unwanted amyloid proteins are removed from
the blood and the plasma is returned to the body. It is only
excess amyloid that gets to the brain that is a concern.
underway and not seeking more patients is a "passive
immunization" study that tests doses of an antibody to
clear beta amyloid from the brains of patients with mild to
also part of a multisite international study of people who
have a genetic risk for Alzheimer’s.
the DIAN Trial, it is still recruiting and will assess safety
of two drugs in people who have a genetic mutation for
inherited early-onset Alzheimer’s disease, which makes up
fewer than 1 percent of total Alzheimer’s cases.
game change is the anti-amyloid therapies themselves,"
Dr. Klunk said. "Without those antibodies or therapies or
imaging technologies, none of these trials could exist."
it’s a critical time now to see results: There are fewer
companies, such as Eli Lilly and GE Healthcare, to pursue
development of imaging tools and drug therapies.
Klunk said he was highly encouraged by recent news from drug
company Biogen Idec, saying an experimental drug was found to
slow down the decline of mental function in Alzheimer’s
patients in a small clinical trial. The drug, aducanumab, was
being tested for safety and not for dosage, but higher doses
of the drug brought better results. It is designed to clear
amyloid plaque from the brain.
might come in two or three years," Dr. Klunk said.
"We’ll see." Dr. Klunk said.