Cognitive Labs

The fog of war
Soldiers from Iraq recover from brain injuries at Palo Alto VA
by Dwana Simone Bain

It was like waking from the dead.
Rigoberto Oceguera knew not where he was or how he got there. Days earlier he was in a Chinook helicopter shot down by a missile near Fallujah, Iraq. Suffering from a ruptured spleen, burns and a fractured pelvis, Oceguera lay broken and dazed in a Washington D.C. military hospital.

But his condition was far worse than broken bones and damaged organs. The 23-year-old also suffered a traumatic brain injury that clouded his mind. The wound brought him to the Palo Alto VA hospital, one of four military care sites in the nation helping soldiers suffering from brain injuries recover their memories and relearn everyday tasks.

For the growing number of soldiers suffering from brain injuries in this war the road to regaining their former lives is difficult, said Dr. Henry Lew of the Palo Alto VA Hospital.

The computer reboots but, "when it reboots, it's not the same programs that were there before," he said.

The person looks much the same as before, but is in many ways different.

Sometimes an injury exacerbates pre-existing personality traits - such as a quick temper. Other times, it creates about-face changes in behavior -- for instance a rowdy person suddenly becomes calm.

Many brain injury patients also experience changes in speech patterns. At times Oceguera struggles for words to express himself. Other times, he speaks with unfiltered frankness.

"A lot of these guys look normal," said Paul Johnson, a clinical coordinator for the VA's Brain Injury Rehabilitation Unit. "Everyone expects them to act normal and be able to be quick about making decisions and speaking.

"Even though they look normal, they've changed and they're unable to function in the ways that they used to function," he added.

Rehabilitating veterans with brain injuries is a relatively new concept, said Lew, the rehabilitation center's medical director.

With an increasing number of soldiers in Iraq surviving explosions and auto crashes -- in large part due to body armor - the need for such treatment is growing.

Recently, the VA central office asked Palo Alto to expand its bed capacity to accommodate anticipated future demand.

The hospital, which began caring for brain-injured soldiers in 1984, has 24 inpatient beds and an outpatient program. The facility treats between 50 and 100 brain injury patients each year from throughout the West Coast, including New Mexico, part of Texas, and the islands of Hawaii and Guam.

Every patient at the hospital is treated by an interdisciplinary team of doctors, nurses, social workers and therapists who help them do everything from recollect their past to remember their daily schedule. The staff will even pray for patients.

"We try to help them as much as we can," said Case Manager Myrlyn Alvarado.

In the rehabilitation program, patients are involved in speech therapy and language groups, reviewing reading, writing and spelling. They participate in computer-assisted training to address deficits in memory, motor skills and reasoning.

Patients also take lessons in math and money management. They improve their social skills and learn community re-entry by rehearsing everyday tasks such as taking the bus, shopping for groceries.

In addition to helping the patients regain or compensate for cognitive deficits, the program offers emotional support. During weekly rap sessions, the patients have a chance to talk about their emotions and frustrations in dealing with a brain injury.

Brain injury patients are tested each week on memory, problem-solving and social interaction. Most stay in the rehabilitation program for about six months.

As patients prepare to leave rehabilitation, a case coordinator helps them with decisions about the future, including planning for housing or transportation and exploring job prospects.

For First Class Platoon Sgt. Alec Giess many of his recollections are uncertain - he can't distinguish the memories from the dreams.

Sitting inside his room at the Palo Alto VA, he flips through several albums of photos he shot in Iraq. Some photos of places and people he remembers well. Others seem familiar but he can't quite place them.

The man who once had a razor-sharp memory uses the photos to help recall what happened only months ago. In December, he was riding shotgun in a five-ton transport truck in Iraq, when the vehicle skidded on the oil-slicked sand. The tipping vehicle ejected Giess and landed upside-down on top of him.

Body armor he'd received just three days earlier spared Giess' life, though he suffered fractured vertebrae and lingering damage to both shoulders.

It wasn't until the 44-year-old father of two returned home to Seaside, Ore. on a 30-day convalescent leave that deeper injuries surfaced.

In the weeks after his accident, Giess operated on a short fuse. He seemed to have trouble remembering things and found himself frequently arguing with this wife, Shana.

"She knew something was wrong," Giess said.

These days, Giess uses a memory book to keep a weekly calendar. It helps him avoid simple problems such as showering three times in one day. And it helps him maintain appointments -- important to a man accustomed to promptness and order.

Brain trauma patients also struggle with slow processing, said Jill Gandolfi, a clinical coordinator in the rehabilitation unit.

A person with slow processing has the ability to complete a task, but it takes longer than usual.

"The world isn't very patient with that," Gandolfi said. "The world is very fast moving out there and not used to waiting three minutes to get a 'yes' answer."

In Iraq, Giess oversaw teams of 75 Iraqis working on building projects. Now, he has trouble doing two things at once, such as flipping through a photo album while carrying on a conversation. And when Giess recently returned home for his daughter Simone's eighth-grade graduation, he found the whirlwind of activity surrounding him overwhelming.

Such difficulties can cause growing frustration within patients, who are sometimes unable to articulate once-simple concepts and find the world treating them differently.

While those who work with brain-injury patients preach the need for compassion and understanding, they also emphasize that each patient be treated in a respectful manner. Often patients complain that people talk "down" to them or address them like children.

"We try to just talk to them like we talk to everyone else," Johnson said.

While acknowledging that rehabilitation has limits, those working with patients said remarkable improvement is possible.

Program Manager Rose Salerno remembers a Navy Seal with a particularly severe brain injury.

"He has since graduated from college, graduate school and he's thinking about going into the CIA," she said.

Oceguera and Giess have both made dramatic improvements in the months since their injuries.

Oceguera, who expected to spend his career in the Army, said he would go back if he could. A proud soldier, he wears a U.S. Army cap pinned with an American flag. He smiles when he talks about his Purple Heart, a decoration given to armed forces wounded in action. He isn't afraid of getting hurt again. His head injury, however, makes him "un-deployable," he explained. Oceguera wants to go to school, to study "something" his brain "can do."

He is also working out everyday, hoping to regain his strength and skill at Tae Kwon Do. An advanced-degree black belt, Oceguera thinks he might coach the sport one day.

Giess -- who spent 24 years in the National Guard -- is also contemplating his future. He owns a small boat and thinks he might start a salmon fishing business. Right now though, he isn't sure how well he can operate the boat.

Potential for future recovery generally depends often on the severity of the brain injury. But there are other factors. Physical fitness makes a difference, the experts say. So does willpower, or as Oceguera calls it "heart."

Lew credits the program with much of the men's progress.

"If you guys had just been lost in the shuffle," he tells them, "You would not be here at this level."

The men seem to agree. The armor may have saved his life - Giess has said - but the program is making him well.

There is an emerging trend to enhance memory in humans through medication, by providing in capsule form ingredients that will affect cognition. Most of these efforts are in the clinical trial phase. Some medications are already on the market (e.g., Aricept). If these efforts are successful, there may be a marked improvement in quality of life. Of course, measuring and tracking improvement over time is important, with an objectively administered system with a protocol or procedure for assessing the impact of subject-learning effects, available here or via our C2 hosted system.

'Smart pills' make headway

By Rita Rubin, USA TODAY
You can rub Rogaine into your scalp to try to regain the hairline of your youth. You can inject Botox into your forehead to smooth time's inroads, at least temporarily. And, some scientists predict, you'll eventually be able to pop a pill to freshen up the inside of your head as well.

Someday soon, if someone jokingly asks you if you remembered to take your smart pill, you can answer yes — seriously.

Thanks to recent strides in understanding how the brain works, it's only a matter of time before medications specifically designed to improve mental ability, or cognition, hit the market.

"The hallmark of these drugs is they don't create more memory," says John Tallman, CEO of Helicon Therapeutics of Farmingdale, N.Y., which plans to begin testing its most promising brain drug in humans later this year. "What these drugs really do is enhance the conversion process of short-term to long-term memories."

Besides Helicon (for the mountain in Greek mythology where Apollo played with the Muses), companies with such evocative names as Sention (apparently a play on sentient, which means conscious or aware) and Memory Pharmaceuticals are focusing on medications to treat patients whose brains are impaired by disease or injury.

But the real market for such drugs might be healthy people who would simply like to be a little quicker on the uptake.

Americans already spend $1 billion a year on dietary supplements claiming to boost brainpower, even though there's little evidence that they work, notes an article in the May issue of Nature Reviews Neuroscience. From vitamin B12 to ginkgo biloba to "BrainQUICKEN" capsules — "used by top students at every Ivy League institution," according to the product's Web site — health-food stores and the Internet are rife with products promising to enhance memory and learning. (Related story: Who should getting a boost in brainpower?)

Once the Food and Drug Administration allows a drug on the market to treat, say, Alzheimer's disease, doctors could prescribe it "off-label" for any purpose they like, including sharpening healthy minds dulled by age or fatigue. And Internet shoppers would have their pick of Web sites selling the drugs without even requiring a prescription.

To an extent, it's already happening. Though it's not clear how widespread the practice is, high school and college students who don't have attention deficit-hyperactivity disorder are taking Ritalin to help cram for exams. Scientists have been known to pop Provigil, approved only to treat narcolepsy, to increase alertness before speaking at professional meetings.

"People are already using a wide range of medical drugs to improve their own performance," says Sention CEO Randall Carpenter, citing Viagra's popularity with men who don't have erectile dysfunction as one example. "It's almost impossible to stop people if they want to do that."

'Normal' cognitive decline

On its Web site, Memory Pharmaceuticals of Montvale, N.J., acknowledges that the potential market for its compounds, one of which is being tested in humans, might extend far beyond patients with Alzheimer's and other memory-robbing ailments. Though 37 million people worldwide have Alzheimer's disease, the company says, more than 180 million — or half of all people over 65 — are experiencing "age-associated cognitive decline."

"This decline is not clearly linked to a definable disease condition and may be a 'normal' part of the process," the company says on its Web site.

Memory Pharmaceuticals raised $35.4 million in its initial public offering this year. President and chief science officer Axel Unterbeck says the medical need alone "would be worth the entire investment" in developing drugs to improve cognition. But he acknowledges that healthy people will seek them out. "This indeed will be a very interesting trend to look at," he says.

Tallman says older people are "very, very concerned about their memories, because their memories are what make them human. No honest person would ever say to you, 'I would never take the drugs.' "

Still, there's no guarantee drugs that work in people impaired by disease would also benefit healthy people who would simply like to recall names more quickly.

For example, first-generation Alzheimer's drugs Cognex and Arricept block the breakdown of acetylcholine, one type of neurotransmitter, a substance that enables nerve cells to communicate with each other. Alzheimer's patients have a shortage of acetylcholine, but people with normal brains do not, so it's not clear what effect the drugs would have on them, says Steven Rose, a director of the Brain and Behavioural Research Group at the Open University in England.

And even if such drugs did enhance cognition in average individuals, Tallman says, "highly functioning people would have probably limited benefit."

Duke University researchers have found that the nicotine patch, approved only to help smokers break the habit, boosts brain function in people with mild to moderate Alzheimer's disease and adults with ADHD and schizophrenia. But earlier tests in healthy volunteers found only a modest effect, says Edward Levin, a professor in Duke's psychiatry and behavioral science department.

Even in Alzheimer's patients, Levin cautions, the nicotine patch's benefits aren't worth the risks. Side effects include an elevated heart rate and blood pressure, sleep disturbances, nausea and dizziness.

The nicotine patch points out another obstacle toward developing "smart drugs" for normal brains. "It has to be as safe as water," Carpenter says. "That's a very daunting task that few people want to try to accomplish."

Perhaps somewhat surprisingly, Stanford University researchers including Dr. Jerome Yesavage found that nicotine gum as well as Aricept, used to treat patients with mild to moderate Alzheimer's, did improve healthy, middle-aged pilots' performance in flight simulators. However, Aricept also can cause side effects that would be pretty undesirable in a pilot, such as dizziness, fainting and vomiting, says pharmacologist Martin Mumenthaler, who led the study.

"The issue is: How do you specifically alter such a complex organ as the brain without affecting anything else?" asks biologist Robert Gerlai, a memory researcher at the University of Hawaii. "The brain doesn't just work on learning and memory. It has all kinds of other functions." In addition, Gerlai and others in the field point out, there is the potential risk that memory-enhancing drugs would work too well, preventing users' brains from distinguishing between important and trivial information.

Some scientists say Helicon's leading drug, aimed at activating a protein involved in the formation of long-term memories, might interfere with short-term memory, Tallman acknowledges.

Animal "memory models are pretty good, but it's hard to really get a total read on human memory without doing human trials," he says. Although Helicon has not yet begun testing its drug in people, Tallman says he suspects that any adverse effects on memory would be transient.

A mental 'jump-start'

Phase I trials, designed to assess the safety of experimental drugs, are conducted in healthy volunteers. So besides monitoring the volunteers for side effects, Sention, of Providence, and Memory Pharmaceuticals are administering tests to assess their drugs' effects on learning and memory.

Mark Bear, a Massachusetts Institute of Technology neuroscientist and Sention co-founder, emphasizes that the Phase I studies were too small to yield robust data about the drugs' effectiveness. Still, he says, "I would be willing to say that the results were very encouraging."

Though it would be unethical for Bear, 46, to test his company's drugs on himself, he does occasionally partake of a medication that might be the first safe and effective smart drug on the market.

Modafinil, sold as Provigil, was approved in 1999 for the treatment of daytime sleepiness in narcolepsy patients. It's not cheap. Web sites sell 30 100-milligram tablets for around $200.

In a small study of healthy men published last year, Barbara Sahakian of the University of Cambridge found that modafinil safely improved performance on tests of memory and attention.

Sahakian says she and her collaborators limited their study to men to eliminate the potentially confounding effect of women's menstrual cycles. But, she says, there's no reason to think that modafinil wouldn't work the same in women.

"It's probably the first smart drug that I've seen," says Sahakian, one of the co-authors of the Nature Reviews article on cognitive enhancers.

Bear says he takes modafinil "to jump-start myself across time zones," not to enhance his mental performance.

He first asked his doctor for a prescription before traveling to a scientific meeting in India. "I had to arrive and give a seminar in the same day. I said to my doctor, 'Look, I'm going halfway around the world. I simply would not be able to function' " without the drug.

Though Bear took modafinil to keep from nodding off in the middle of his presentation, he acknowledges that "anything that increases alertness will increase cognition."

And anyone who has downed a double espresso — or two or three — while studying for an exam or writing a report would probably drink to that.