Brain Power

Posted by The Editorial Desk / Thursday, February 19th, 2009

We spend our lives creating memories that can be stolen by age. The goals we set for our children can be interrupted by delays. Fortunately, the region’s physicians are working hard toward improving the lives of Alzheimer’s and Autism patients. These are their stories—and their patients’…

By Jill Brigati, Jan Linley, Jonathan Hunley / Photography by Jonathan Timmes

Alzheimer’s Disease
When will we be out of the woods?

By Jan Linley

Entering the world of Alzheimer’s disease feels a bit like walking into the woods of a futuristic Grimm’s fairy tale, except that the future is now. Starting out the path is clear, but deeper into the forest the way becomes obscured, the surroundings ever shifting. And it is here in the heart of the woods where the stealthy beta-amyloid plaques and tau-protein tangles of Alzheimer’s begin the process of stealing memories and altering identities.

Dr. Scott Turner, director of the Memory Disorders Program at Georgetown University Medical Center, pointed out that “you see this huge tidal wave of Alzheimer’s coming, so we’re going to be up to 14 to 15 million by 2050. And that’s just the U.S.”

Deep in the Woods
Alzheimer’s is nothing if not complex. Researchers do not know what causes it or exactly how it works, but they are learning more all of the time.

Our brains are like an intricate switchboard with billions of neurons that send signals through branches that connect the nerve cells to one another at trillions of points. With Alzheimer’s disease this system is literally short-circuited by an accumulation of plaques that clog the flow of information, and tangles that fill and kill the neurons. Beta-amyloid is the protein responsible for forming microscopic plaques in a brain with Alzheimer’s disease, while tangles are formed from another protein called tau. Healthy brains also create these proteins, but turn them over on a regular basis so there is minimal or no accumulation. What scientists are finding now is that these proteins are only part of the story.

According to Dr. Mark TeKrony, diplomate of the American Board of Psychiatry and Neurology of the Neurology Center of Fairfax, “Over the past 10 years researchers have identified deficiencies of blood flow to the brain, deficiencies of nicotinic receptors, inflammation, oxidative stress related to mitochondrial dysfunction, and accumulation of amyloid proteins.”

Following the Bread Crumbs
Reg Heitchue of Reston recounted that his first clue that his wife Jean was having trouble came through a friend who was helping her clean up after a party. She told Reg that Jean seemed to take a long time loading the dishwasher. He started to pay attention and noticed changes, including slower, more labored speech. That was a little over five years ago when Jean, now 73, was diagnosed with Alzheimer’s. Reg, 72, and Jean celebrated their 50th anniversary in November 2008.

Alzheimer’s typically reveals itself through memory loss and behavioral changes. This is because it starts in the temporal lobes and hippocampus, the area of the brain responsible for creating new memories. But memory loss may not be the first symptom that reveals itself.

It is common for a spouse or other family member to be the first to seek medical help. Dr. James Bicksel, of Comprehensive Neurology Services in McLean, explained that “a lot of times people with early dementia don’t have the insight into the fact that this is happening, or they want to deny it or pass it off as just age.”

From start to finish, caregivers act as companions and guides on the journey of this disease. To care for the people they love, they’re advised to also care for themselves by keeping active with work and outside interests, and making use of available resources as needed. Ray can’t speak highly enough of the Fairfax County Adult Day Health Care Centers, where Jean spends four days a week while he is at work. “She loves it.”

Jan Evans of Arlington takes her husband, Bill, to Iona House in Northwest D.C. two days a week.

Evans and her second husband, Bill D., had their fifth wedding anniversary in September of last year. They were married just a month when, at his annual physical, Bill’s physician shared with Jan that Bill would have memory problems. “Now I guess that’s as gently as they could say it, and I was in shock.” Bill was 82 at the time; Jan, 70. A year later Bill was diagnosed with vascular dementia, the result of several mini-strokes, and a year after that he was diagnosed with Alzheimer’s disease. This type of dual dementia diagnosis is not unusual. Heitchue’s wife Jean also has vascular dementia as well as Parkinson’s.

Anna and Sam Nissen of Columbia, Md., who celebrate their 50th wedding anniversary this year, went to the National Institutes of Health in 2003 because Sam, 72, was experiencing symptoms of Alzheimer’s. Anna, also 72, said they “were going to see if he had MCI [mild cognitive impairment], but they came up with a diagnosis of Alzheimer’s.”

Currently Sam does not need outside caregiving. Always active, he still plays tennis and enjoys gardening.

Both Sam and Bill D. are in clinical trials at Georgetown University Hospital. All clinical trials are double blind, meaning 50 percent of participants will get placebos. Bill has been in a clinical trial for two years to test the efficacy of omega-3 fatty acids. Evans has not noticed a difference in Bill since the beginning of the trial, possibly because he got a placebo. Sam just started his second trial, testing an Eli Lilly gamma secretase inhibitor drug that blocks one of the enzymes involved in the beta-amyloid synthesis. If it works, the drug would stop the production of plaques in its tracks. Heitchue looked into getting Jean into a trial “not because I thought it would help her so much [at that point], as for the greater good.” Jean did not qualify because her Alzheimer’s was too advanced.

The Way Out
Current drugs may slow the progression of Alzheimer’s for some patients, but the results are underwhelming. “With medicines like Aricept, Razadyne and Exelon, about 20 percent of the patients do better than if they’d taken nothing at all. In addition, the degree to which they get better is only about 10 to 20 percent above the patients who are not on medicine,” Bicksel explained. Dr. James Cooper, associate clinical professor at George Washington University, echoes that it’s debatable whether any positive effect from the drugs outweighs the costs of the medicine, but he sways toward using them.

The four doctors interviewed believe there is a way out of the woods, and all four expect an effective drug or drugs in the next 10—maybe as little as five—to 20 years. What are they most excited about?

Turner sees promise in the vaccine strategies—either active or passive immunizations—and the gamma secretase inhibitors such as the one being tested in the Eli Lilly clinical trial that Sam is in. Both active and passive vaccines are intended to reduce the beta-amyloid protein buildup. Turner and Cooper are hopeful about the possibility of a cocktail of drugs used to treat Alzheimer’s.

The National Institute on Aging is undergoing a trial that Tekrony is excited about, one he says will address the potential genetic causes of Alzheimer’s. The procedure involves “attempting to collect samples from thousands of Alzheimer’s disease patients to attempt to find genetic linkage.” He believes the database the NIA is building “will finally start to look beyond the long-standing belief that [Apolipoprotein E] and amyloid protein are causative for the disease and may finally identify a cluster of genes or promoter genes [those that cause expression of another part of the genome] that are common in patients with [Alzheimer’s disease].”

Cooper also mentioned a study using methylene blue, a dye that in the past has been used as a biological stain, among other things. “It seems to have helped people with Alzheimer’s disease. It’s interfering with a co-conspirator, tau. If you knock that out, maybe that’s eliminated one of the foundations of Alzheimer’s.”

Bicksel looks to medicines on the horizon that will “interfere with the cascade of how those plaques and tangles are made,” cutting the problem off at the source, or that will “sop up those plaques or take up the bad beta-amyloids that get deposited in the brain before they can coalesce and form plaques.” Bicksel is also excited about plans to create a dementia center at Fairfax Hospital to improve the care of dementia patients.

On the doctors’ wish list is a biomarker that would quickly diagnose Alzheimer’s and eliminate or abbreviate the current relatively lengthy neurological testing process. “We want something like a pregnancy test for Alzheimer’s disease,” Turner said.

Because of the nature of the course of Alzheimer’s, the clinical trials—in order to measure appreciable results—often last between 12 and 24 months, so practical issues of logistics and time may foil participation in them. Some patients do not want to be guinea pigs. Others take the risk for posterity. And of course it’s a gamble both whether the drug will work and whether the patient is receiving the drug or a placebo. Still, in order for the bright future to become a reality, there needs to be more funding and greater participation in clinical trials.

Bicksel leaves us with this happy thought about where Alzheimer’s is headed: “I think there will be incredible opportunity to help people in dramatic ways in the future.”

According to the Alzheimer Association’s Abstract 2008 Alzheimer’s Disease Facts and Figures

By Jan Linley

As many as 5.2 million people in the United States are living with Alzheimer’s.

Ten million baby boomers will develop Alzheimer’s in their lifetimes.

Every 71 seconds, someone develops Alzheimer’s.

Alzheimer’s is the sixth-leading cause of death.

One in six women and one in 10 men who live to be at least age 55 will develop Alzheimer’s disease in their remaining lifetimes.

The direct and indirect costs of Alzheimer’s and other dementias to Medicare, Medicaid and businesses amount to more than $148 billion each year.

Hi-Tech Wizardry to Boost Your Memory

By Jan Linley

The jury is out about the effectiveness of high-tech programs and games to boost memory. However, the general thinking is they can’t hurt, and they may even help. Here are a few with buzz to consider. Most have online demos.

Posit Science
www.positscience.com; $395
Offers two software programs, each with a variety of exercises designed to enhance brain performance. The Brain Fitness Program Classic targets the auditory system of the brain, while InSight is for the brain’s visual processing system.

HAPPYneuron
www.happy-neuron.com; $9.95 (monthly subscription)
Provides online brain games designed to slow the natural degenerative cognitive effects of aging.

MindFit
www.e-mindfitness.com $139-$149
Designed to “strengthen brain function and slow cognitive loss.”

iMusic
www.vth.biz/driver/imusic; $29.95-$800
“The ultimate brain igniter” uses music to enhance brain performance.

Brain Age2 by Nintendo
Requires Nintendo DS; $19.99
Claims to exercise the brain by using a variety of activities “designed to increase blood flow to the brain.

Top 10 Ways to Boost Brain Function

By Jan Linley

Physical exercise helps maintain healthy weight, cholesterol and blood-pressure levels and stimulates the brain.

Exercise your brain like you would your body. Learn new skills and hobbies, anything that challenges you to expand and use your brain in new ways.

Keep socially active. Stay connected to and involved with other people.

Don’t smoke and if you drink, do so in moderation (up to two drinks per day maximum).

Eat a healthy diet high in fruits and vegetables and low in fat.

Avoid head injuries. If you bike or ski, wear a helmet. If you’re elderly take precautions to avoid falls.

Keep stress levels at a minimum. Chronic stress causes the adrenal glands to produce high levels of cortisol, which are thought to be harmful to the brain.

Get plenty of rest. Like your body, your brain is rejuvenated by sleep.

Engage in neurobics, exercising the brain by doing things in unique ways:

• Drive to work a different route,
• Get dressed with your eyes closed,
• Brush your teeth or dial the phone with the other hand.

Laugh. It makes you feel good and may even improve your memory.

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Through Their Eyes
Autistic children see the world in multiple puzzle pieces

By Jonathan Hunley

One in 150. That’s how many children are diagnosed with autism in this country, making it more common than pediatric cancer, diabetes and AIDS combined, according to advocacy group Autism Speaks. The puzzle-piece logos adorning awareness ribbons and, sometimes, even NASCAR racecars, mark autism as an especially significant topic to this region, as some of the world’s foremost doctors and researchers work to help parents and children see through a similar lens.

That’s a tall order.

Just ask Karen Gorman. Like many Northern Virginia parents, she had some homework to do before selecting a private school for her oldest child.

But unlike a lot of parents in the region, she wasn’t necessarily interested in a certain religious curriculum, athletic program or alumni network. Gorman had to find the right mix of social and academic ingredients because her son Patrick has Asperger’s syndrome, an autism spectrum disorder.

She settled on the Ivymount School in Rockville, Md., and Patrick, who turns 14 on Feb. 9, is learning to cope with social situations as his family continues to learn how to live with his medical condition.

The Scholastic Blur
Gorman began to notice something about her eldest son when he was about 3. There was more than one way to reach the family’s then-home in Arlington by car, but Patrick would “have a meltdown” if his mom didn’t drive the route he thought to be correct: i.e., if she broke the routine.

“He would be screaming, ‘No! No! No! Go back! Go back!’” the 44-year-old mother of three recalled.

Then when Patrick went to preschool, he had trouble engaging in class and didn’t always grasp social cues. He was also irritated by loud noises and sometimes flapped his hands excitedly.

All of these behaviors are characteristics of autism, and at 5, Patrick was diagnosed with Asperger’s. The syndrome is less severe than the stereotype of autism—more serious cases include deficiencies in language skills, for example—but because it’s still on the autism spectrum, it’s plenty frustrating.

By the end of first grade, it was clear that Patrick would have to leave the private school he was attending. He then went to public school, but even special-needs classes didn’t work out, and in third grade, things started to fall apart.

One day, when a teacher was trying to prepare the class to get ready to go home, he made the mistake of saying something like: “It’s time to go.” Patrick took the comment literally. He headed for the door, and when a teacher punished him, his mother knew it was time to head to another school.

Independent special-needs schools were the next stop on Patrick’s “educational odyssey,” but none were the right fit for a student with Asperger’s, Gorman said. Finally, the Gorman family found Ivymount. Patrick is in his third year in the Model Asperger Program there, which succeeds in filling his need for social skills instruction.

The program is just one of several ways Patrick has been helped by Lauren Kenworthy, director of Children’s National Medical Center’s Center for Autism Spectrum Disorders in Rockville. Kenworthy evaluated Patrick, and she and the staff at Children’s have been an “invaluable” help for the Gorman family of five as they’ve developed the routines that often are necessary for someone with autism.

“I don’t know where I’d be if it weren’t for them,” Gorman said.

Diana, who chose to withold her last name, can relate.

Her 14-year-old son, Ben, has a tremendous aptitude in math, but the difficulties Asperger’s has brought him have meant he had to find a school that fit—and a team of professionals that could aid him.

That’s where Kenworthy and Dr. Peter Daniolos come in. Diana refers to the 46-year-old Children’s staffers by their first names in an interview—but not out of disrespect for Kenworthy’s doctoral degree or Daniolos’ position as medical director of the Center for Autism Spectrum Disorders. They simply have become that integral to her family.

“I don’t know where we would have been if we hadn’t found Lauren and Peter,” Diana said.

The clinicians have given Ben and his family recommendations on how to live with Asperger’s and have been able to reduce medical jargon to terms that both parents and children can understand.

“She’s just brilliant, and she just really gets a handle on these subtle things that I would never figure out,” the 45-year-old mother of two said about Kenworthy.

Kenworthy and Daniolos also helped the family find a behavioral expert that has smoothed the rough road of living with special-needs children. In addition to Ben’s frustrations, Diana’s daughter, 12-year-old Rachel, has struggled with attention-deficit and anxiety issues. That makes for more than a full plate for Diana and her husband. Behavioral therapy should help Ben in the future. He’s doing well at H-B Woodlawn, the legendary alternative public school in Arlington for grades six to 12, and Diana says Ben’s team is confident he can thrive in spite of Asperger’s. “He does have something to contribute to this world,” she said.

Seeing the Forest for the Trees
Indeed, though autistic children often can’t focus on the big picture, Daniolos said, “these conditions also bring many gifts to these kids.”

To wit: Youngsters with milder forms of autism are frequently called “little professors” for behavior that might seem odd or aloof to others, but they often are proficient—sometimes obsessed—with facts and figures. According to Kenworthy, a major question then becomes: “How would these skills be useful in the world?”

Daniolos recalled a boy fascinated by floor buffers who won an award for cleaning a building. Kenworthy mentioned another story of someone who was an expert on appliances. While harnessing these useful traits, the program at Ivymount School boosts practical functions of the brain such as flexibility, Kenworthy said. Asperger’s can induce such rigidity that a student can be thrown off just by, say, the presence of a substitute teacher.

That single change can prompt student fears: Will lunch be cancelled? Can I still go home at the end of the day? So Ivymount teaches flexibility step by step, to have in place a plan B if plan A fails.

“When we do that, they become much more functional kids,” said Kenworthy, a member of the Model Asperger Program’s professional advisory board.

Specialists See the Big Picture
Just as a team of experts is the prescription for autism patients, Dr. Roger Packer says working relationships in a medical facility are key to combating overarching problems.

Packer, executive director of the Center for Neurosciences and Behavioral Medicine at Children’s, says it used to be that specialists operated independently of each other as if toiling in “silos.”

At Children’s, those “artificial walls” are gone, which means that for problems without easy solutions, doctors and researchers can collaborate. That’s especially beneficial in cases of autism, which Packer says is probably the No. 1 reason a child would be seen by a member of his staff.

“This is a major health issue for children throughout the region,” he said. That means patients benefit from the work of minds such as Dr. William Gaillard and Joshua Corbin in addition to seeing Kenworthy, Daniolos and their peers. Gaillard is part of a team using functional magnetic resonance imaging to show what parts of the brain are used for certain tasks. By using a traditional MRI machine, Gaillard can examine how blood flow changes as children with Asperger’s or autism perform tasks. On the scan, different parts of the brain light up as the children work. After collecting data on what brain systems are affected, doctors then hope to use the information to target specific treatments.

Children’s started working with this technology, in conjunction with Georgetown University, about six years ago. Some of the study participants have been the youngest autistic children observed with fMRI in the country.

Their willingness to be a part of the project aids researchers, and, in return, Gaillard says, some children “get a more thorough evaluation than they would clinically.”

A Lighted Road Ahead
Corbin, a developmental neurobiologist, examines the brain on a more basic level. He and post-doctoral fellow Luis Olmos are looking at gene mutation associated with Fragile X, a family of genetic conditions related to autism.

Fragile X involves the mutation of a single gene, whereas multiple mutations are found in autism, so the Children’s research seeks to explain more about both disorders.

Corbin and Olmos study the brains of mice with the mutated genes in an effort to relate the findings to humans.

“This is one of the fastest-growing fields in neuroscience, without a doubt,” said Corbin, principal investigator at the Center for Neuroscience Research at Children’s Research Institute in Washington.

What’s not growing fast enough is governmental help for families dealing with mental health issues, Sheila Kuders said.

Kuders has become an advocate for more public programs as she has raised three children with a host of mental health concerns, including autism.

She doesn’t understand why the government can find money for other matters while mental-health funding suffers. She could get aid in a medical emergency, but that’s not the point, she said. “Why do you have to wait for an emergency to have your needs met?”

She was encouraged to take up this fight by Dr. Gary Spivack, founder and medical director of Columbia Associates in Psychiatry and clinical director of child and adolescent services at Dominion Hospital. He has cared for all her children: 21-year-old David, 19-year-old Christina and 17-year-old Steven.

“He’s one of the best clinical psychiatrists around,” said Kuders, who lives in Burke. In a large practice such as Columbia, Spivack sees more patients suffering from anxiety and depression than ones who have autism. The disorder makes up only about 5 percent of the practice. But that doesn’t mean it’s a slam-dunk to treat.

“There’s not a blood test that tells you about it,” Spivack said.

And though medications can help with symptoms such as aggressiveness, there’s no magic cure in a pill.

That doesn’t bother Dr. Darshan S. Khalsa, co-owner of Khalsa Integrative Medicine in Reston. As an acupuncturist and doctor of Oriental medicine, he can’t legally prescribe drugs. But autistic children come to him for treatment, sometimes because their families are fed up with lackluster results from what Khalsa refers to as “Western medicine.” He uses herbs and enzymes targeting the immune and digestive systems, in the traditional Eastern method of helping someone achieve balance, at which point the body can heal itself.

“In a sense, we do no healing at all,” said Khalsa, who has been practicing for 10 years.

Sometimes he can help autistic patients; other times, he will refer them to nearby Western practitioners.

“There’s no one answer for every autistic child,” he said.

But he and his counterparts continue to seek what answers are out there.

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The Mystery and Misery of Migraines
Regional studies could reveal answers and offer relief

By Jill Brigati

Red taillights blaze through the windshield as you stew in Toll Road traffic, you just realized that you left tonight’s paperwork at today’s meeting, and a text from home pops up on your PDA  “wondering” what is for dinner—everyday stresses, everyday headaches. So when, if at all, do we start to worry that our “regular” headaches might mean that something more sinister is about to strike?

MIGRAINES. The word alone has the power to cause sufferers like Rochelle Taylor, 35, to shudder. For the past 10 years migraines have affected every facet of her life. “Even walking hurts. It feels like your brain is bumping against your skull,” she said. A tension headache is bothersome, but a migraine “brings you down,” according to the Fairfax technology trainer.

Taylor met neurologist Dr. Eric Sklar at Inova Fairfax Hospital, where she had been admitted for vertigo after two weeks of non-stop migraines last summer. Sklar prescribed both preventative and rescue medications for Taylor, who now experiences migraines barely once a month.

A sure fix has eluded doctors for centuries, in part because so many variables come into play. Intensity, duration and intervals between migraines vary during a person’s lifetime. Situational stressors affect every migraineur differently. Response to medication is unpredictable.

To treat a full-blown migraine, doctors often prescribe triptans, pharmaceutical migraine-specific “blockbusters.” “One triptan might have no effect on a patient, then we try a different one in its class, and it’s the best thing they’ve ever taken,” Sklar said. Their expense can be a wallet-buster; one pill costs up to $20 and insurance companies generally do not pay for more than a handful per month.

Taylor takes a preventative beta-blocker three times a day, every day. She takes a triptan when a migraine starts to emerge. Taylor credits Sklar’s treatment strategy with reducing the severity of her attacks.

Tracy Templer, an Alexandria social worker who “can’t remember not having a headache,” says the best thing about Sklar is that he listens. “We just don’t go through a checklist. He wants my opinion,” she said.

Templer, 35, is no longer hypersensitive to head pain. The rare times she gets a headache she takes an ibuprofen “like a normal person. I’m not going for the little blue box every 24 hours anymore.”

No One Can ‘Give’ You A Migraine
Alicia Pfund, of Silver Spring, Md., had migraines “most days” for more than 40 years. She thought it was normal; her mother suffered with the disease too. “When I would go to the doctor I didn’t talk about my headaches,” Pfund said.

Two years ago Pfund, 68, found relief with Botox injections at the Headache Clinic at George Washington University Hospital, (GWUH). Today her migraines are mild and infrequent. She sees clinic director Dr. Perry Richardson every four months for injections. “I’m going to stretch it to five. I’m feeling good,” she said with a smile.

Richardson explains that some people are primed from birth to be susceptible to the disease. “There is a software glitch in our brains that is a completely nonadaptive orchestration of biology,” Richardson said. During a migraine the brain releases chemicals that heighten sensitivity in cerebral nerves and dilate blood vessels.

The brain’s high-achieving region no doubt hosts a multitude of aggravating factors, conditions that exacerbate migraines but do not cause them. “Stress lowers the threshold for triggering a migraine,” Richardson clarified.

The Latest Research … Happening Here
Lisa Hamilton, of Annapolis, Md. suffered with migraines since fourth grade. She described a life of crippling pain, ruined relationships and outrageous attempts at relief. “I attached a belt from my head to a doorknob and pulled. I ran red lights because it hurt too much to brake,” she said.

Last year Hamilton, 45, became Dr. Marc Schlosberg’s first patient in a Washington Hospital Center clinical trial, part of a national study to determine if a certain “hole in the heart,” patent foramen ovale (PFO), is responsible for some migraines.

Schlosberg says preliminary results look promising. “In terms of frequency of headaches, Lisa was an amazing success,” the doctor reported. Hamilton has gone from having 10 headaches per month down to one.

Dr. Jim Thompson, lead cardiology investigator in the Inova Fairfax Hospital PFO trial, explains that researchers stumbled upon the PFO/migraine connection while studying PFO/stroke patients who reported their migraines vanished after their PFOs were closed. “They were more thrilled about their migraines being gone than reducing the risk of stroke,” Thompson said.

At GWUH’s Headache Clinic, Richardson oversees a trial to evaluate if Botox injections relieve migraines by blocking pain signals. Migraineurs have found relief using Botox “off-label” but it is not yet approved as a migraine-specific treatment. “Most patients are reporting that their migraines are easier to treat and they are not getting as many of them,” he said.

Richardson says that the disease is “on the credibility map for scientific investigation” and findings will soon serve a larger population. “Because we’re uncovering the underlying biology of migraines, the therapies will have application to chronic pain in general,” he said.

(February 2009)

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