There isn’t a single, effective long-term treatment for Alzheimer’s disease, so it seems unrealistic to plan on preventing this widespread form of dementia by 2020. But an American father-and-son team with much experience in brain disease and epidemiology – Dr. Zaven and Dr. Ara Khachaturian – think it can be achieved, with a lot of brain power and billions of dollars. And they want Israel to be part of it.
There were other massive projects that took a decade or less to accomplish, such as the US Transcontinental Railroad in the 1860s (seven years); the Panama Canal in the early 1900s (10 years); the Manhattan Project for the atomic bomb to end World War II (six years); the Apollo Program to get America on the moon before 1970 (eight years); and the Human Genome Project (by 2000) in a decade.
Thus, said the Khachaturians in a recent interview with The Jerusalem Post
at Jerusalem’s Inbal Hotel, “it isn’t so outlandish to take only 10 years to prevent elderly people from getting Alzheimer’s – or at least to delay its onset long enough so that it’s like prevention because people will die of something else.”
THEY WERE at the hotel for a few days to convene a think
tank for establishing an international research consortium called the
Campaign to Prevent Alzheimer’s Disease by 2020 (www.pad2020.org).
Attended by delegates from Israel, the US, Europe and Russia, the
meetings were intended to form a partnership with leading Israeli
physicians and scientists in the field.
Additional meetings are planned over the next six months to
explore the feasibility of designing a prototype for a comprehensive
international database on healthy aging. This will greatly enhance
efforts by scientists and biotechnology companies to develop valid
diagnostic tests as well as therapies that delay or ultimately prevent
the onset of many chronic diseases that affect memory, movement and
mood. “If we can delay the onset of mental disability by only five
years, we can cut the costs by half,” said Zaven.
Around the world, there are 34 million victims of Alzheimer’s and
other types of dementia; five or six million live in the US, and about
100,000 in Israel. But many post-World War II Baby Boomers now entering
retirement are likely to live into their 90s, so Alzheimer’s will
become an even more severe problem unless something is done to stop it.
THE US National Institute on Ageing describes
Alzheimer’s as an irreversible, progressive brain disease that slowly
destroys memory and thinking skills and eventually even the ability to
carry out the simplest tasks. In most people with Alzheimer’s, symptoms
first appear after age 60. Dementia, which can be caused by other
factors such as insufficient oxygen to the brain, is the loss of
cognitive functioning – thinking, remembering and reasoning.
Alzheimer’s, the most common type of dementia, was
named in 1906 after Dr. Alois Alzheimer, who conducted a pathology
examination of the brain tissue of a woman who had died of an unusual
mental illness. Her symptoms had included memory loss, language
problems and unpredictable behavior. The physician found many abnormal
clumps (now called amyloid plaques) and tangled bundles of fibers
(called neurofibrillary tangles) in her brain. Plaques and tangles are
two of the main features of Alzheimer’s. The third is the loss of
connections between nerve cells.
still don’t know what triggers Alzheimer’s, it is known that brain
damage can begin as many as 20 years before problems appear. As more
and more plaques and tangles form in particular brain areas, healthy
neurons begin to work less efficiently. They eventually lose their
ability to communicate with each other and they die. This process
spreads to a nearby structure, called the hippocampus, which is
essential in forming memories. As more and more neurons die, affected
brain regions begin to shrivel. By the final stage of Alzheimer’s,
damage is widespread and brain tissue has shrunk significantly. Memory
problems are one of the first signs of Alzheimer’s, but people have
problems with memory as they age even without Alzheimer’s, so diagnosis
can be certain only at autopsy.
progresses, memory loss continues, and changes in other cognitive
abilities appear. Problems can include getting lost, having trouble
handling money and paying bills, repeating questions, taking longer to
complete normal daily tasks, poor judgment, and small mood and
personality changes. People are often diagnosed in this stage.
In moderate Alzheimer’s, damage occurs in sections of
the brain that control language, reasoning, sensory processing and
conscious thought. Memory loss and confusion increase, and people begin
to have problems recognizing family and friends. They may be unable to
learn new things, carry out tasks that involve multiple steps (such as
getting dressed), or cope with new situations, and may have
hallucinations, delusions or paranoia.
severe final stages, plaques and tangles have spread throughout the
brain, and brain tissue has shrunk significantly. Victims cannot
communicate and are completely dependent on others. Near the end, the
person may be in bed most of the time as the body shuts down.
SCIENTISTS ARE investigating associations between
cognitive decline and vascular and metabolic conditions such as heart
disease, stroke, high blood pressure, diabetes and obesity.
Understanding these relationships and testing them in clinical trials
will help us understand whether reducing risk factors for these
diseases may help with Alzheimer’s as well.
though there is no cure, early diagnosis is beneficial for several
reasons, since there are medications that slow the decline, and
families can make plans for living arrangements, financial and legal
matters and developing support networks.
Alzheimer’s medications have been approved so far by the US Food and
Drug Administration: donepezil (Aricept), rivastigmine (Exelon) and
galantamine (Razadyne) for mild to moderate Alzheimer’s and memantine
(Namenda) for the moderate-to-severe stage. These drugs work by
regulating neurotransmitters, and may help maintain thinking, memory
and speaking skills – but they don’t change the underlying disease
process and may help only for a few months or years.
The worldwide cost of caring for dementia patients is estimated at
over $400 billion a year, $3 billion in Israel alone. With the ageing
of the population, dementia is a looming catastrophe. PAD2020, a
non-profit organization based in Rockvillle, Maryland, gets financial
support from the Helen Bader Foundation (which was previously involved
in funding early childhood development) and the US Alzheimer’s
Association, plus at least one “educational grant” from a
pharmaceutical company. But the elder Khachaturian asserted that the
drug firm is allowed absolutely no influence on policies. “It’s clearly
a hands-off policy. We’re applying to most major drug companies and
foundations for financial support, as we insist that the project not
become the monopoly of any single company or institution,” Zaven
insisted. The US government, aware of the urgency, is expected to
eventually donate much of the funding.
Khatchaturian (the surname is Armenian), a neuroscientist who
specialized in brain ageing, worked at the University of Pittsburg and
became director of Alzheimer’s research at the US National Institutes
of Health. Ara, an expert in epidemiology and biostatistics at Johns
Hopkins, joined his father to serve as a founding trustee and executive
vice president of PAD2020 because he believes in the cause.
“STATISTICS ALONE don’t present a full picture of the
destructive effects of these illnesses,” said Zaven, a leader of
neuroscience research programs for more than 30 years who is now
president of PAD2020. “Brain mechanisms were my scientific interest,
and when I was sent to the NIH Institute on Ageing, I was asked to
develop strategic planning on brain ageing. Alzheimer’s was not well
known then, and few scientists were interested in it. I created most of
Current therapies, he continued,
“provide symptomatic relief [only] in the short run. We know that high
cholesterol and high blood pressure are early warning signals of heart
disease, but we have no proven markers for early-stage dementia. New
approaches that identify incipient disease, and novel therapies that
will prevent or modify the progression of brain cell death and the
onset of the most disabling symptoms are urgently needed.”
Zaven had been to Israel only once before, for a short
visit, and Ara’s arrival was his first. So why did they think Israel
was a natural partner? “Because it’s an important place for Alzheimer’s
research. The population is small enough and manageable, and Israelis
have a relatively long life expectancy. The country,” added Zaven, “has
a solid scientific infrastructure and much successful involvement in
medical research. There is a great deal of fantastic medical talent
here. Israel could be a prototype for a partnership linking the US and
Europe.” The Israel Alzheimer’s Association has voiced its support, he
Specifically, the Khatchaturians want
healthy Israelis in their 30s or 40s whose parents were diagnosed with
Alzheimer’s to volunteer to be observed over years so information on
their mental function can be gathered. “They would be called in for an
examination, imaging, blood tests and neurological and cognitive
assessments every year so changes could be determined. We also intend
to look for biological markers that can predict who is likely to get
the disease,” added Ara.
In the US, said Zaven,
there are people with a family history of dementia who are actually
keen on being examined because they fear they have inherited it. Dr.
Alan Roses, a neurologist at Duke University in North Carolina, has
discovered a susceptibility gene for Alzheimer’s, said Zaven, “but one
gene alone is not enough to cause the disease. It occurs in combination
with environmental factors and additional genes.”
Despite the large number of victims, it is amazing that there is
no national Alzheimer’s database. “This is needed to record cognitive
changes,” said the father. “Doctors take their blood pressure, but
don’t examine brain function.”
PAD2020 is at
too early a stage to determine where the money needed will come from,
but Zaven believes one billion dollars a year over 10 years would be
enough. That’s only a drop in the bucket compared to the costs of
treating and minding Alzheimer’s patients.
Khatchaturians are unwilling to be involved in a repeat of the Decade
of the Brain established by the first Bush Administration in 1980 that
“produced absolutely nothing. There was a lot of hoopla and many
meetings, but it lacked a strategic plan. The dementia situation has
gotten a lot more severe since then.”
The project poses various
ethical problems, such as the fact that
people participating in research have to know that in the future, their
personal data could lead to the development of medications. “The data
will be preserved anonymously, but we need to develop solid safeguards
to ensure privacy,” Ara said.
It will not be a simple struggle. US medical investigators said last
week that there is “no firm evidence” that any
preventive measures are effective. The independent panel convened by
the NIH said many measures including mental stimulation, exercise and a
variety of dietary supplements have been studied, but the value of such
strategies in delaying the onset or reducing the severity of decline
has never been demonstrated by rigorous studies.
“We wish we could tell people that taking a pill or doing a puzzle
every day would prevent this terrible disease, but current evidence
doesn’t support this,” said Prof. Martha Daviglus, the panel’s chairman
and a preventive medicine expert at Northwestern University.