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orine Reed had worked at a Portland apparel

company for two years when she noticed

something strange happening. She'd start a

routine task and forget what came next, as

if she had driven into a mental fogbank.

Her primary care doctor chalked up Norine's memory

problems to stress and told her not to worry; we all forget

things as we get older.

But Norine's problem just seemed to grow. Her large,

boisterous family (her son-in-law affectionately calls them "the

loud family") noticed that Norine was telling the same stories

over and over, as often as three times in a single evening.

She started gerting lost, even in heLown neighborhood in Troutdale, Ore. "

Her grown daughter, Christine, remembers when her mother

was driving them to Target just a few blocks away from Norine's

home. "She went to turn left at the light when we were supposed

to turn right," Christine says. "I said, 'Where are you going?' She

said, 'I don't know.' She forgot where we were going. She forgot

where she was."

Norine's memory problems began to take a toll on her 33-year

marriage to Todd, a friendly security system salesman.

"She'd ask me something about my job, then completely forget

what I told her," he says. "I thought she was just not paying

artention to me. That she didn't care."

But it was a routine medical appointment that sounded the

final alarm. On the day of her checkup, Norine arrived at the

clinic to find a sign on the door directing patientS to a new

address. When she found the new location, she told her doctor,

"You moved and didn't tell me!"

"Norine," the doctor said. "We moved a long time ago.

You've been here since then."

The physiciarl referred Norine to neurologist Michael

Mega, M .D., Ph.D ., medical director of Providence Cognitive

www.providence.org/toget her

Assessment Clinic at Providence Brain Institute. After a series

of tests, ranging from pencil-and-paper quizzes to sophisticated

brain scans, Dr. Mega delivered the diagnosis on Feb. 9, 2009.

As orine sat with Todd, Dr. Mega showed them a scan of

a healthy middle-aged brain, then a brain of an 80-year-old.

Norine's brain looked more like the 80-year-old's. Her

hippocampus, the center in the brain where memory is formed,

was shrinking. Norine had rare early onset of Alzheimer's disease,

a degenerative disease that destroys memory, reasoning, thinking

and eventually the body's ability to function . It strikes the vast

majority of its sufferers after age 65, and the average life

expectancy after diagnosis is 10 years.

Norine and Todd were in shock, then in tears.

Norine's thoughtS immediately turned to her grandmother, who

has dementia and requires 24-hour help. "I don't want to live like

that," she told Todd, "where somebody has to take care of me."

Aiming to cure the cause What the Reeds didn't know then is that researchers at Providence

Brain Institute had begun testing a new treatment for people in the

early stages of Alzheimer's disease - a treatment that, if successful,

would reverse some of the disease's devastating symptoms and

delay itS progression.

The research is the latest in a growing understanding of the

condition, which got itS name in 1906 when German neurologist

and psychiatrist Alois Alzheimer identified a progressive,

degenerative brain disease that had no known cause or cure.

Until then, Alzheimer's was lumped in with the broader category

of dementia, and was considered a natural part of aging. "Many people think that dementia and Alzheimer's disease are

equal," Dr. Mega says. "It's not true. There are about 50 different

causes of dementia - Parkinson's disease, stroke, vitamin B-12

deficiency, hypothyroidism, some types of infections. Some are

reversible; some are not." > > >

PROVIDENCE TOGETHER I 23

What distinguishes Alzheimer's disease from other forms of

dementia is the presence of clumps of toxic proteins in the brain,

believed to be the cause of the disease. O ne of these proteins is

the sticky "beta-amyloid which binds together to form plaque

between nerve cells. Another protein creates tangles rather than

plaques. Researchers suspect that both tangles and plaques play

important roles in the formation of Alzheimer's disease.

In the 1980s Alzheimer's research made a giant leap fOlWard

when scientiStS discovered a gene mutation in some families that

causes carriers to produce excessive amounts of the amyloid

protein. Arlasr researchers could isolate that defective gene,

inject it into mice, and study the effects of the beta-amyloid

protein and plaques on a living creature.

As research progressed in human trials, scientists discovered that

aearments to eliminate beta-amyloid protein and plaques didn't

have much effect on people with late-srageAlzheimer's. By then the

damage to the brain had been done and couldn't be reversed. Anti­

amyloid treatments might, however, benefit people in the early stages.

Fortunately, better diagnostic testing now allows doctors to detect

Alzheimer's earlier, when the toxic proteins are just beginning to have

an effect. The research trials at Providence Brain Institute are targeted

for people with very early Alzheimer's disease and its precursor,

mild cognitive impairment. Support for this research comes from

Providence St. Vincent Medical Foundation. If successful, these

treatments can be given long before toxic proteins and plaques cause

irreparable damage - a potential breakthrough in treating Alzheimer's.

"If these new agents delay the decline from m ild cognitive

impairment to Alzheimer's disease by merely five years,"

Dr. Mega says, "then the prevalence of Alzheimer's disease

in our society will be cut in half' - .

"1 was losing my best friend" In the weeks afrer her diagnosis, Norine hadn't yet enrolled in a

clinical trial at Providence. She was still reeling from the news,

which hit her husband as hard as it did her.

"I was losing my best friend," Todd says quietly. "It seemed like

the end of the world at that point. She was going to fade away

and forget who I was."

The couple met when they were both 20. Norine worked as a

computer operator at the University of California, Los Angeles.

She was on her way home one night when she decided to Stop by

the Air National G uard base to visit a young man she had a crush

on. Instead, a new guy was working the shift - Todd Reed.

"She acrually laughed at my jokes," he recalls. "I just said, 'H ey, if you have nothing to do, why don't you just stay around and talk?'"

The pair was inseparable from then on. They were engaged a

month later and married within six months.

They had four children, Christine, Mindy, Marthew and Eric.

They built a life together and watched as their own parents and

grandparents aged. Even as Norine's grandmother developed a

non-Alzheimer's dementia, Norine never thought she'd develop

a similar illness, and certainly not at age 51 .

By the time she was diagnosed, Norine's ability to work had

deteriorated to the point that she took a voluntary layoff. Although

she didn't suffer the visual or spatial misperceptions common with

Alzheimer's disease, she stopped driving for fear of gerting lost.

Now she and Todd threw themselves into batding the disease

in whatever way they could. orine bought every vitamin and

supplement that Dr. Mega suggested. She worked on lowering

her stress, which has a damaging effect on the brain. She did

brain teasers to help grow new neural networks to replace those

killed by beta-amyloid protein. And she began taking Aricept, an

Alzheimer's medication that sometimes sharpens mental acuity.

The couple joined an Alzheimer's support group for patients

and their families, but found the experience unnerving.

"It was hard listening to the people who were further along

than I was," Norine says.

"You see your future, and you're heading toward it," Todd adds.

"You can't stop it," Norine says, "It's like a train."

Continued on pagl 27 > > >

The brain of someone with Alzheimer'S disease has fewer nerve cells, and is clouded by abnormal proteins.

Likewise, twisted fibers found inside the brain's cells (the dark areas inside the cell, pictured lower right) prevent nutrients

In a healthy brain, beta-amyloid protein is broken down and eliminated. In Alzheimer'S disease, protein fragments accumulate to form hard, insoluble plaques that block synapses from firing.

24 I PROVIDEN CE TOG ETHER

and other important substances from traveling between nerve cells.

Scientists are not certain if plaques and tangles cause cell death in the Alzheimer'S brain, but they're the prime suspects.

www.providence.org/together

"It's normal to be forgetful as we get older," says neurologist Michael Mega, M.D., Ph.D., from the donor-supported Providence Cognitive Assessment Clinic. "The question is, what is abnormal?"

It's a question that comes up when we lose our car keys, or even our car. But the degenerative disease of Alzheimer's encompasses far more than typical memory loss, and symptoms often come much earlier than the diagnosis.

If someone is showing signs of cognitive impairment, this simple test can be a reliable indicator: How many animals can you name in one minute?

"When you score fewer than 15 animals in one minute, that imparts perhaps a 20-fold increased risk of going on to develop Alzheimer's disease," Dr. Mega says. "A normal 75-year-old will name about 18 animals in a minute. Most 40-, 50- and 60-year-olds will name in the mid-20s."

Dr. Mega and the national Alzheimer's Association share some other early warning signs:

• . . . .. Typical: Forgetting names or appointments, but remembering them later Unusual: Forgetting information recently learned; repeatedly asking for the same information; using memory aids such as notes for routine events

Typical: Making a mistake balancing your checkbook or forgetting how to program a VCR Unusual: Having trouble following a familiar recipe or keeping track of monthly bills; getting lost going to a familiar place; forgetting the rules of a favorite game

www.providence org/together

. .. . . . . Typical: Occasionally feeling tired of family or social obligations; becoming irritable Unusual: Unexplained depression, particularly if you've never had a history of depression; lack of motivation; lax grooming; loss of interest in things you once enjoyed; unexplained anxiety and fearfulness

• • Typical: Forgetting the day of the week but remembering it later Unusual: Losing track of dates, seasons and the passage of time; forgetting where you are or how you got there

Typical: Occasionally losing a pair of glasses or a remote control Unusual: Putting things in unusual places, such as the remote in the refrigerator; an inability to retrace your steps to find what you lost

• • Typical: Sometimes struggling to f ind the right word Unusual: Forgetting the point of a conversation; calling things by the wrong name such as a "hand clock" instead of a watch

A remarkable change Six months afrer diagnosing Norine's condition and stabilizing

her medication, Dr. Mega suggested she enroll in a clinical trial

for an antibody called bapineuzumab (pronounced bap-ah-NEW­zu-mab). Bappi, as it's called, is an antibody produced by rabbits

that binds to the beta-amyloid protein and removes it from the

brain. It's in the last phase of testing before possible approval by

the U.S. Food and Drug Administration.

As with many clinical trials, this one has a necessary catch:

Norine wouldn't know whether she was getting the antibody or a

placebo. The blind approach helps determine if a given treatment

is working.

She agreed without hesitation and began receiving infusions

evety 13 weeks. After her first infusion, she didn't notice any

change except for a migraine headache. It was possible that she

had been given an inert substance, the placebo. H er second

infusion seemed about the same at first.

Shortly afrerward, her daughter Christine asked her mother

how many infusions she'd had.

"Two," Norine replied.

The significance of that answer was almost imperceptible, but it

didn't escape Christine. Her mother had remembered the number.

After the third infusion, other positive signs began to emerge.

Norine would start to tell a story and stop herself. "Did I tell you

this?" she'd ask "That's right, I did."

Norine became aware that she wasn't getting lost as often. The

fatigue that had drained her during the months before the diagnosis

and forced her to nap before and afrer work was going away.

Her friends noticed that the shuffling gait she had developed

also was disappearing. By now it was irrefutable: the fog in

Norine's brain was beginning to lift. "I was able to read again," Norine recalls. "Before starting the

trial, it would take me months to even read a skinny paperback

because I couldn't remember what I'd just read." After the third

infusion, "I started realizing that I was able to understand. That's

how I knew I was getting better."

Dr. Mega doesn't know for certain ifNorine is getting the

antibody, but a battery of tests given every three months confirms

that Norine is regaining her cognitive ability.

Nearly two years afrer she began the clinical trial, Norine has

regained many of the abilities she had lost. She no longer relies

on the written reminders that used to guide her through each day.

And afrer some gentle prodding by Todd, she is driving again,

starting with shorr trips to the nearby coffee shop.

She's considering going back to school to get a master's degree

in apparel design, a project that would continue to exercise her

mind. In the meantime, she has taken a temporary job with

another apparel manufacturer.

"There's a possibility that the stress might be too much,"

Norine says of her new job. "lEI start to feel like it's too much,

I won't continue."

"We're taking it a day at a time," Todd says. "There are no

guarantees. But I'm so gratefUl for Providence, for Dr. Mega,

for the study. We got our life back Whether it lasts for 30 years,

or 10 years or 10 more months, we've gOt our life back" _

On the seem that heart disease and Alzheimer'S have little in common. It turns out, however, that they share many of the same risk factors.

To lower your risk, Dr. Mega suggests adopting these

ingnew things creates new networks in the brain, much like new growth shoots on a tree. This is a defense against the plaque-building beta-amyloid protein, which does the opposite by pruning

Foods containing omega-3 fatty acids, for instance, help brains function, while a diet high in saturated fats is believed to help beta-amyloid plaques grow.

t:}.ealthM habits:

www.providence.org/together

the neural network.

. - • Stress hormones shrink the hippocampus, which is the brain's memory circuit and the part most affected by Alzheimer's disease.

PROVIDENCE TOGETHER I 27