Holding back the darkness

A new campaign aims at preventing Alzheimer’s.

By JUDY SIEGEL-ITZKOVICH
human brain mind 248.88 (photo credit: )
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.
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 thinktank for establishing an international research consortium called theCampaign to Prevent Alzheimer’s Disease by 2020 (www.pad2020.org).Attended by delegates from Israel, the US, Europe and Russia, themeetings were intended to form a partnership with leading Israeliphysicians and scientists in the field.
Additional meetings are planned over the next six months toexplore the feasibility of designing a prototype for a comprehensiveinternational  database on healthy aging. This will greatly enhanceefforts by scientists and biotechnology companies to develop validdiagnostic tests as well as therapies that delay or ultimately preventthe onset of many chronic diseases that affect memory, movement andmood. “If we can delay the onset of mental disability by only fiveyears, we can cut the costs by half,” said Zaven.
Around the world, there are 34 million victims of Alzheimer’s andother types of dementia; five or six million live in the US, and about100,000 in Israel. But many post-World War II Baby Boomers now enteringretirement are likely to live into their 90s, so Alzheimer’s willbecome an even more severe problem unless something is done to stop it.
THE US National Institute on Ageing describesAlzheimer’s as an irreversible, progressive brain disease that slowlydestroys memory and thinking skills and eventually even the ability tocarry out the simplest tasks. In most people with Alzheimer’s, symptomsfirst appear after age 60. Dementia, which can be caused by otherfactors such as insufficient oxygen to the brain, is the loss ofcognitive functioning – thinking, remembering and reasoning.
Alzheimer’s, the most common type of dementia, wasnamed in 1906 after Dr. Alois Alzheimer, who conducted a pathologyexamination of the brain tissue of a woman who had died of an unusualmental illness. Her symptoms had included memory loss, languageproblems and unpredictable behavior. The physician found many abnormalclumps (now called amyloid plaques) and tangled bundles of fibers(called neurofibrillary tangles) in her brain. Plaques and tangles aretwo of the main features of Alzheimer’s. The third is the loss ofconnections between nerve cells.
Although westill don’t know what triggers Alzheimer’s, it is known that braindamage can begin as many as 20 years before problems appear. As moreand more plaques and tangles form in particular brain areas, healthyneurons begin to work less efficiently. They eventually lose theirability to communicate with each other and they die. This processspreads to a nearby structure, called the hippocampus, which isessential in forming memories. As more and more neurons die, affectedbrain regions begin to shrivel. By the final stage of Alzheimer’s,damage is widespread and brain tissue has shrunk significantly. Memoryproblems are one of the first signs of Alzheimer’s, but people haveproblems with memory as they age even without Alzheimer’s, so diagnosiscan be certain only at autopsy.
As Alzheimer’sprogresses, memory loss continues, and changes in other cognitiveabilities appear. Problems can include getting lost, having troublehandling money and paying bills, repeating questions, taking longer tocomplete normal daily tasks, poor judgment, and small mood andpersonality changes. People are often diagnosed in this stage.
In moderate Alzheimer’s, damage occurs in sections ofthe brain that control language, reasoning, sensory processing andconscious thought. Memory loss and confusion increase, and people beginto have problems recognizing family and friends. They may be unable tolearn new things, carry out tasks that involve multiple steps (such asgetting dressed), or cope with new situations, and may havehallucinations, delusions or paranoia.
At thesevere final stages, plaques and tangles have spread throughout thebrain, and brain tissue has shrunk significantly. Victims cannotcommunicate and are completely dependent on others. Near the end, theperson may be in bed most of the time as the body shuts down.
SCIENTISTS ARE investigating associations betweencognitive decline and vascular and metabolic conditions such as heartdisease, stroke, high blood pressure, diabetes and obesity.Understanding these relationships and testing them in clinical trialswill help us understand whether reducing risk factors for thesediseases may help with Alzheimer’s as well.
Eventhough there is no cure, early diagnosis is beneficial for severalreasons, since there are medications that slow the decline, andfamilies can make plans for living arrangements, financial and legalmatters and developing support networks.
FourAlzheimer’s medications have been approved so far by the US Food andDrug Administration:  donepezil (Aricept), rivastigmine (Exelon) andgalantamine (Razadyne) for mild to moderate Alzheimer’s and memantine(Namenda) for the moderate-to-severe stage. These drugs work byregulating neurotransmitters, and may help maintain thinking, memoryand speaking skills – but they don’t change the underlying diseaseprocess and may help only for a few months or years.
The worldwide cost of caring for dementia patients is estimated atover $400 billion a year, $3 billion in Israel alone. With the ageingof the population, dementia is a looming catastrophe. PAD2020, anon-profit organization based in Rockvillle, Maryland, gets financialsupport from the Helen Bader Foundation (which was previously involvedin funding early childhood development) and the US Alzheimer’sAssociation, plus at least one “educational grant” from apharmaceutical company. But the elder Khachaturian asserted that thedrug firm is allowed absolutely no influence on policies. “It’s clearlya hands-off policy. We’re applying to most major drug companies andfoundations for financial support, as we insist that the project notbecome the monopoly of any single company or institution,” Zaveninsisted. The US government, aware of the urgency, is expected toeventually donate much of the funding.
ZavenKhatchaturian (the surname is Armenian), a neuroscientist whospecialized in brain ageing, worked at the University of Pittsburg andbecame director of Alzheimer’s research at the US National Institutesof Health. Ara, an expert in epidemiology and biostatistics at JohnsHopkins, joined his father to serve as a founding trustee and executivevice president of PAD2020 because he believes in the cause.
“STATISTICS ALONE don’t present a full picture of thedestructive effects of these illnesses,” said Zaven, a leader ofneuroscience research programs for more than 30 years who is nowpresident of PAD2020. “Brain mechanisms were my scientific interest,and when I was sent to the NIH Institute on Ageing, I was asked todevelop strategic planning on brain ageing. Alzheimer’s was not wellknown then, and few scientists were interested in it. I created most ofthe programs.”
Current therapies, he continued,“provide symptomatic relief [only] in the short run. We know that highcholesterol and high blood pressure are early warning signals of heartdisease, but we have no proven markers for early-stage dementia. Newapproaches that identify incipient disease, and novel therapies thatwill prevent or modify the progression of brain cell death and theonset of the most disabling symptoms are urgently needed.”
Zaven had been to Israel only once before, for a shortvisit, and Ara’s arrival was his first. So why did they think Israelwas a natural partner? “Because it’s an important place for Alzheimer’sresearch. The population is small enough and manageable, and Israelishave a relatively long life expectancy. The country,” added Zaven, “hasa solid scientific infrastructure and much successful involvement inmedical research. There is a great deal of fantastic medical talenthere. Israel could be a prototype for a partnership linking the US andEurope.” The Israel Alzheimer’s Association has voiced its support, hesaid.
Specifically, the Khatchaturians wanthealthy Israelis in their 30s or 40s whose parents were diagnosed withAlzheimer’s to volunteer to be observed over years so information ontheir mental function can be gathered. “They would be called in for anexamination, imaging, blood tests and neurological and cognitiveassessments every year so changes could be determined. We also intendto look for biological markers that can predict who is likely to getthe disease,” added Ara.
In the US, said Zaven,there are people with a family history of dementia who are actuallykeen on being examined because they fear they have inherited it. Dr.Alan Roses, a neurologist at Duke University in North Carolina, hasdiscovered a susceptibility gene for Alzheimer’s, said Zaven, “but onegene alone is not enough to cause the disease. It occurs in combinationwith environmental factors and additional genes.”
Despite the large number of victims, it is amazing that there isno national Alzheimer’s database. “This is needed to record cognitivechanges,” said the father. “Doctors take their blood pressure, butdon’t examine brain function.”
PAD2020 is attoo early a stage to determine where the money needed will come from,but Zaven believes one billion dollars a year over 10 years would beenough. That’s only a drop in the bucket compared to the costs oftreating and minding Alzheimer’s patients.
TheKhatchaturians are unwilling to be involved in a repeat of the Decadeof the Brain established by the first Bush Administration in 1980 that“produced absolutely nothing. There was a lot of hoopla and manymeetings, but it lacked a strategic plan. The dementia situation hasgotten a lot more severe since then.”
The project poses variousethical problems, such as the fact thatpeople participating in research have to know that in the future, theirpersonal data could lead to the development of medications. “The datawill be preserved anonymously, but we need to develop solid safeguardsto ensure privacy,” Ara said.
It will not be a simple struggle. US medical investigators said lastweek that there is “no firm evidence” that anypreventive measures are effective. The independent panel convened bythe NIH said many measures including mental stimulation, exercise and avariety of dietary supplements have been studied, but the value of suchstrategies in delaying the onset or reducing the severity of declinehas never been demonstrated by rigorous studies.
“We wish we could tell people that taking a pill or doing a puzzleevery day would prevent this terrible disease, but current evidencedoesn’t support this,” said Prof. Martha Daviglus, the panel’s chairmanand a preventive medicine expert at Northwestern University.