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When Fading Memory Raises Questions, Neuropsychology Can Point to Answers

10.16.2012

Susan Harvell's daughter, Claire, can't list specific moments when her mother, a longtime human resources executive in her early 50s, seemed to be off her game. "It wasn't anything drastic," she said. "She could tell you a million stories about when I was 3 years old, but if I told her I was going to do something, she'd ask me five minutes later if I was going to do something."

Many of her friends' mothers were about the same age, she said, "and they would tell me, 'My mom asked me the same thing 5,000 times.' That's why I didn't think anything was too different."

"I know there's a lot more in our future around this, too," said Susan Harvell's husband, Dave Baker. "Every day we just get up and do the best we can, and where we end up is in somebody else's hands."

Harvell's husband, Dave Baker, became concerned when he saw that his highly intelligent wife wasn't just asking him the kind of computer questions that all non-technical folks ask; instead, she was posing questions about content. Her emotions around her work had altered, too. "She'd been a very confident, capable individual and she was becoming more anxious and upset and worried," he said. "It started to become obvious that something was changing."

Baker was like many people who notice such differences, and begin to look for answers, especially as advancing age begins to interfere with the dozens of daily tasks once youthfully taken for granted. In the United States, more than 40 million people are over 65 years old; another 80 million are age 45-64. Of all the diseases related to age, dementia may be the most feared—a condition that attacks the core of all those qualities that distinguish one person from another and erodes those memories that bind together families and friends.

You can have a quick assessment in a doctor's office—and that's good, but it's not as sensitive as the whole battery of tests you get in a neuropsychological evaluation.

-Stanford neuropsychologist Gayle Deutsch, PhD

Dementia can take many forms; Alzheimer's disease is the most often diagnosed variety and its toll is rapidly rising. The Alzheimer's Association estimated that in 2011 5.4 million Americans—about one in eight of those 65 or older—were living with its consequences. Researchers have yet to understand what triggers the imbalance in brain chemistry that degrades its normal function, shrinking its overall size, and depositing tangles and plaques that block the millions of daily neuronal interactions. Progress has been made, however, in diagnosing the disease. Until recently, physicians were left only autopsy for definitive diagnosis. Now, at facilities like Stanford Hospital & Clinics' Center for Memory Disorders, where Harvell was advised to seek care, patients have new options that, in combination with traditional tests, provide a much earlier sense of direction.

Looking for answers

"My job is to try and figure out first if there's anything we can fix right away," said Geoffrey Kerchner, MD, PhD, a behavioral neurologist who became Harvell's doctor. "When a patient comes to me with a complaint about memory, my approach is like that of any physician—I have to understand what medicines they're on, what surgeries they've had, what their thyroid function or vitamin B12 levels are—to try to discover what the cause could be."

Harvell's tests included an MRI to look for signs of a stroke or other brain injury. All came back with no obvious cause for her cognitive struggles. The next step, Kerchner said, was objective neuropsychological assessment, a set of tests that solve the dilemma for many who wonder if their memory lapses are something to worry about.

Susan Harvell's daughter, Claire, can't list specific moments when her mother seemed to be off her game. "It wasn't anything drastic," she said. "She could tell you a million stories about when I was 3 years old, but if I told her I was going to do something, she'd ask me five minutes later if I was going to do something."

The hospital's neuropsychology service, where Harvell was evaluated, does assessments on adults and children. It is focused on the cognitive and behavioral effects of conditions including head injury, cerebrovascular disease, multiple sclerosis, dementia, brain tumor, Parkinson's disease, epilepsy and attention deficit/hyperactivity. Its expertise is essential in the diagnostic process.

Harvell "is vibrant and carries on a lively conversation," Kerchner said, "and it's difficult in the course of a routine medical appointment to see that there's anything the matter."

"When we look at behavior and the brain, we find there's a complex inner relationship," said Stanford neuropsychologist Gayle Deutsch, PhD. "A lot of our behaviors  become automatic over our lifetime, but when we break them apart, there is a great deal of complexity." Deutsch began the process of teasing apart the components of cognition to ascertain where Harvell's problems truly began. That territory includes intellectual and executive function, language skills, visual-spatial abilities, attention, memory, motor skills and mood. Deutsch begins with a set of tests that take into account a full range of demographic information used to distinguish those changes that emerge with normal aging and those linked to neurodegenerative conditions. 

The tests themselves are designed to evaluate, in the most straightforward way, how the mind is working. Just reading out loud, for example, won't show much. "Pronouncing words is something that is less sensitive to age-related cognitive decline," Deutsch said. A hallmark of Alzheimer's disease, however, is a decline in the brain's ability to retain new information, so the tests Deutsch administers challenge how long someone can remember a list of words or reproduce a set of shapes, or follow directions.  As Deutsch moves to test executive function, she will engage a patient's family and friends for their observations. "Our tests are good at measuring conceptual reasoning and problem solving," she said, "but it's also important to look at everyday behavior. Are people showing social skills appropriate for their age? Sometimes people with different kinds of dementia may seem to be less careful about reading social cues. Or they may become apathetic and show no interest in activities. That can't always be measured in a standardized test."

COULD YOU HAVE ALZHEIMER'S DISEASE?

Worrying about Alzheimer's is something more and more of us are doing.  Age-related cognitive decline happens to most of us: As we get older, we might forget why we went into the kitchen or the name of a character in a movie. That's normal. Some of us might do that more than others, but typically, that's about as far as our forgetfulness goes. Here are some basics about Alzheimer's and dementia to consider:

  • Alzheimer's affects short-term memory most dramatically. Asking the same question over and over again is a hallmark of that loss of function.
  • Brain scans might show some physical changes indicative of Alzheimer's, but cognitive tests are the only way to objectively measure functional changes.
  • Memory loss is often accompanied by a loss of executive function: the ability to plan a task and then complete it. Losing the ability to call things by their names is another indicator.
  • Changes in personality also emerge. Someone once very calm and steady may become irritable, sad, anxious, impulsive or apathetic.

What Else Might Cause Cognitive Impairment?

  • Medications, on their own or in combination, may produce dementia-like symptoms. These symptoms can appear suddenly or over time.
  • Thyroid imbalance, hypoglycemia, too much sodium or calcium, dehydration and nutritional deficiencies can also trigger changes in cognition and emotional state.
  • Brain tumors and bleeding between the brain and its lining can interfere with brain function; so can lack of oxygen to the brain, originating with heart and lung problems. Other health issues, including smoke or carbon inhalation or coma, can have an impact on brain function.

What Tests Can Help

  • Physical exam, including blood and organ function tests, along with a complete medical history, is helpful in ruling out a treatable medical condition.
  • MRI, CT and PET scans provide more detail; an EEG (electroencephalogram) tracks electrical activity in the brain through electrodes attached to the scalp. Spinal fluid may also be tested.
  • Neuropsychological and psychiatric evaluation complete the picture.

What the data showed

Going through a full evaluation is really the only way to pinpoint what's going on, Deutsch said. "You can have a quick assessment in a doctor's office—and that's good, but it's not as sensitive as the whole battery of tests you get in a neuropsychological evaluation. And having that knowledge puts you and your family in the right direction to get the right treatment."

While the tests Deutsch conducts allow very specific measurements of brain dysfunction, standard brain imaging doesn't show the atrophy classic to dementia until middle to late stages of the disease. But two new tests are now available that analyze levels of two proteins in the body associated with Alzheimer's disease—amyloid beta and tau. "The cerebral spinal fluid test is an example of a new test that actually looks for abnormalities that are caused by the disease itself," Kerchner said, "so it can provide positive evidence of the disease." A second test, just approved by the FDA, uses radioactive particles that seek out and mark amyloid plaques in the brain. Those two tests, he said, are so sensitive to Alzheimer's that for select patients they may reduce the need for other tests.

Finally came the moment when, as Harvell remembers it, Kerchner "got nose to nose with me, got very serious and told me I wouldn't be working anymore," that she had early onset Alzheimer's. She was 53. "He was very thorough about outlining the tests they'd done and what each test meant and how he came to his conclusion that she had Alzheimer's," Baker said. "There wasn't a lot of doubt when he said it."

"I was upset at first," Harvell said. "I was surprised. I was in denial. I thought the whole party was over—work and everything. I can't work. I can't drive. It was like everything was going past me. It's hard."

Baker said, "The day we got the diagnosis we came home and Susan's sister and brother-in-law had come to visit and we didn't know whether to tell them or not. We were kind of just sitting there in shock, and I think for a number of months there was this shock, and this mourning. We did a lot of crying and mourning and a lot of being upset. We've moved through that now and we're just looking for the positive sides, for how we can help other people going through this disease, how Susan can help with research and how we can just enjoy ourselves in our day."

Having an answer helps a patient understand more about their prognosis and what's likely to happen in the coming years—and we have a lot of data and understanding about that.

-Stanford behavioral neurobiologist Geoffrey Kerchner, MD, PhD

Kerchner agrees with others in the memory disorder care community that within a decade biomarker tests, such as the ones that show elevated levels of Alzheimer's particular chemistry, will likely become part of standard screening tests, as colonoscopies are now part of every 50-year-old's health exams. Until then, the current combination of physical and neuropsychological exams will remain the best and most critically important avenue to diagnosis, especially "with the rising prevalence of concern," Kerchner said. "We get more and more referrals from people with mild symptoms who are worried—the husband who keeps losing his cell phone, for instance. Your scores could mean you're completely within the norm for your age. Or, it could mean that you started out life being very smart, so the testing can be insensitive as to whether it's a decline for you. In that case, having those tests done can be extremely valuable as a baseline."

Finding Peace

"Having a garden and a dog is really healthy if you're going through something like this," said Susan Harvell. "I read. I paint. I have things to do. I have great friends."

Being diagnosed with Alzheimer's "is a big hit," Kerchner said, "but by the time a patient has a physician tell them, 'I think you have Alzheimer's disease,' it's not a mystery to them that something's going on with their brain. They know it and they're worried. Having an answer helps a patient understand more about their prognosis and what's likely to happen in the coming years—and we have a lot of data and understanding about that. I think people achieve a lot of peace of mind in having a name on what they have and in being acknowledged by the medical community."

"Having a garden and a dog is really healthy if you're going through something like this," Harvell said. "I read. I paint. I have things to do. I have great friends. My job right now is to go to Stanford and do what I need to do with Dr. Kerchner, to be there for somebody, to have conversations. It's good to connect with someone else who's going through what you are so you don't just feel like, 'Oh, it's just me. I'm the purple goose going down the street.' I want to get it out and talk about it—to be a waving flag for Alzheimer's and for Stanford."

The garden in particular gives her a sense of purpose and reward. "I see the color every day and I'm like, 'Life is beautiful.'"

"I know there's a lot more in our future around this, too," Baker said. "Every day we just get up and do the best we can, and where we end up is in somebody else's hands." Baker was diagnosed with heart failure several years ago, and his condition has been stabilized. "There were some advances in therapies and I'm still around," he said. "We're really hoping the same thing can happen for Susan's disease—and that at least we can help get there for all the people who have Alzheimer's as well."

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