The Oncoming Medical Disaster…With No Cure In Sight

The helplessness of Alzheimer's Disease.
Elderly man seated, rear view, hand held to head.
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"Stròlic Furlàn" - Davide Gabino via flickr |

Joel Shurkin, Contributor

Editors' note: This is part one of a three-part series on Alzheimer's disease and the current state of research and treatment. Part two is available here and part three here.

(Inside Science) -- The great plague is coming. After 100 years of research and billions of dollars spent around the world, we still have no protection and there is none on the horizon.

The coming public health disaster is Alzheimer's disease and other forms of dementia. Alzheimer's already is the sixth leading cause of death in the U.S., the fifth leading cause for Americans over the age of 65, and these ranks may even be higher, as death certificates may underreport the actual number of cases. In 2010, according to the Centers for Disease Control and Prevention, 83,494 Americans died of it, and it was a contributing cause of 26,488 more deaths. The cost of health care to treat Alzheimer's that year was $200 billion and is heading to the trillion dollar mark.

Around 40 million people have a form of dementia world-wide. Dementia is a broad term for cognitive decline, the inability to think, reason, and remember. More than half the cases are Alzheimer's. Other types include vascular, Lewy body and frontaltemporal dementias.

Because people are living longer and Alzheimer's is generally a disease of age, the number of cases is expected to grow quickly. The result could be catastrophic.

The country that is most likely to be hit the hardest is Japan. With a shrinking, aging population, it is predicted that by 2060 more than 40 percent of the population will be over the age of 65 -- prime candidates for Alzheimer's and other dementias.

The disease is expected to become so prevalent that it may disrupt Japan's economy and society if no treatment is found, according to Takaomi Saido, team leader at the Laboratory for Proteolytic Neuroscience at Riken University, quoted in the newspaper, Japan Times.

The first patient

Alzheimer's disease was first identified at the end of the 19th century, when a German woman, a homemaker named Auguste Deter, showed signs of mental deterioration well before such symptoms typically make their mark. She was 51, much too early for senile dementia.

When she died, Alois Alzheimer, a neuropathologist, and his partner, Emil Kraepelin, did an autopsy and found that Frau Deter's brain was clogged with lumpy, oval-shaped clumps, plaques of the protein beta-amyloid and tangles of a protein now known as tau. The men agreed the new disease would be named after Alzheimer.

There are several forms of Alzheimer's, a relatively rare kind that runs in families; an early-onset variety that strikes in mid-life (about five percent), and the more common disorder found in people — more likely women — later in life, usually people in their 70s and 80s.

Beginning very early in life, people naturally acquire a damaging substance called tau in the brain. It has been found in children as young as 10 years old, said Eric Karran, Director of Research at Alzheimer's Research UK, Britain's leading dementia research charity.

"What we think happens, everyone — you, I, everyone we consider normal — has tau abnormalities in the brain," he said. By itself it does not do enough damage to make a difference. As we get older, it is likely responsible for the normal, age-related memory loss many people experience. Symptoms include common complaints like losing keys and misremembering names.

But, if there is another "provocation," the deposition of amyloid, an amino acid, the result is far more severe. The tau creates the tangles that clog the brain and the beta amyloid forms the plaques. Nerve cells die and the brain loses a lot of tissue.

The reason there is such a long time between the beginning of the disorder and the symptoms, Karran said, is in part because of the plasticity of the brain. As the amyloid does its damage, the brain compensates. If one neural pathway doesn't work, the brain finds a detour. That works until there are no more detours and the damage becomes evident in the patient's behavior.

Two people can have the same apparent damage but one has mental difficulties and the other doesn't. Scientists think people have a cognitive reserve, and people who use their brains, are well-educated and use analysis in their work, are less likely to be affected. At least, that is how the reasoning goes.

Yet, many very bright active people get Alzheimer's, including the writers Iris Murdoch and Terry Pratchett (who died of it earlier this month), artist Norman Rockwell, and the composer Aaron Copland. The victim in the best-selling novel and film Still Alice, is a linguistic professor. Her condition is totally plausible.

A lack of effective treatment options

Four drugs have been approved to treat Alzheimer's in the U.S. Their use is somewhat controversial among neurologists because they do not work very well, if at all. They seem to slow the progression of the disease for some people for a while and then stop working. Like drugs for Parkinson's, they treat symptoms of the disease, but not the underlying pathology. Nonetheless, they are the only treatments for Alzheimer's.

Three of the drugs are called cholinesterase inhibitors, which essentially protect against the depletion of acetylcholine, a neurotransmitter involved in communication between brain cells. Acetylcholine plays a role in memory and learning. The best known because it is widely advertised is Aricept, available generically as donepezil. Two other similar drugs are Razadyne (galantamine) and Exelon (rivastigmine). 

The British National Institute for Clinical Excellence withdrew approval of donepezil in 2005 for use in mild to moderate Alzheimer's disease, saying there was no evidence it did any good. They changed their minds a few years later and permitted its use for moderate cases of Alzheimer's. It still is prescribed for mild to moderate Alzheimer's in the U.S. as well as for more severe stages of the disease.

The other drug is Namenda. Called an NMDA-receptor antagonist, which protects healthy nerve cells from the neurotransmitter glutamate. Alzheimer's patients have too much glutamate that overstimulates cells.

There is no way to measure the effectiveness of the drugs — there is no reliably accurate test for Alzheimer's the way a doctor could see someone's temperature go down after taking medication, or measuring sugar in the blood. The drugs do not appear to alter anything; if they work at all, they treat the symptoms while the disease continues to kill brain cells. One huge study in the United Kingdom showed the drug-induced plateau lasts about nine months if it works at all. Karran said the drugs were tested on an efficacy measurement scale ranging from 1 to 70 and registered between 2.5 and 3, hardly anything.

Nechama Bernhardt, a Towson, Maryland neurologist, in private practice, who prescribes the drugs, said it is almost impossible to determine their efficacy. For instance, most people with Alzheimer's also are depressed, and depression can lead to cognitive impairment. Sometimes, it is the first symptom noticed. If the patient is successfully treated for depression and at the same time they undergo Alzheimer's treatment, the impairment improves and physicians can't tell whether it was the depression medicine or the Alzheimer's drugs.

Doctors still prescribe the available Alzheimer's drugs because they are cheap (available in generic form) and that's all they have to offer.

In fact, it is not only Alzheimer's that is the threat, said Bernhardt.

"We have no cures for any of the neurodegenerative diseases, including Parkinson's and ALS [amyotrophic lateral sclerosis or Lou Gehrig's disease]," she said.

So after all these years, and all the research, there is no cure and no real treatment. Why?

This is the first story in a multi-part series about the current state of research into and treatment of Alzheimer's disease. Part two explores the catch-22 of Alzheimer's diagnosis and treatment. 

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Joel Shurkin is a freelance writer in Baltimore who has also taught journalism and science writing.