Holding back the darkness

By
May 8, 2010 18:51

A new campaign aims at preventing Alzheimer’s.




human brain mind 248.88

human brain mind 248.88. (photo credit:)

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.

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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.

Although we 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.

As Alzheimer’s 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.

At the 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.

Even 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.

Four 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.

Zaven 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 the programs.”

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 said.

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.

The 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.

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