B. New Techniques Help in Diagnosing AD

A healthy man in his early 60s begins to notice that his memory isn't as good as it used to be. More and more often, a word will be on the tip of his tongue but he just can't remember it. He forgets appointments, makes mistakes when paying his bills, and finds that he's often confused or anxious about the normal hustle and bustle of life around him. One evening, he suddenly finds himself walking in a neighborhood a couple of miles from his house. He has no idea how he got there.

Not so long ago, this man's condition would have been swept into a broad catch-all category called "senile dementia" or "senility." Today, the picture is very different. We now know that Alzheimer's and other illnesses with dementia are distinct diseases. Armed with this knowledge, we have rapidly improved our ability to accurately diagnose AD. We are still some distance from the ultimate goal - a reliable, valid, inexpensive, and early diagnostic marker - but experienced physicians now can diagnose AD with up to 90 percent accuracy.

Early diagnosis has several advantages. For example, many conditions cause symptoms that mimic those of Alzheimer's disease. Finding out early that the problem isn't AD but is something else can spur people into getting treatment for the real condition. For the small percentage of dementias that are treatable or even reversible, early diagnosis increases the chances of successful treatment.

Even when the cause of the dementia turns out to be Alzheimer's disease, it's good to find out sooner rather than later. One benefit is medical. The drugs now available to treat AD can help some people maintain their mental abilities for months to years, though they do not change the underlying course of the disease (see the section Helping People with AD Maintain their Mental Functioning for more on these drugs).

Other benefits are practical. The sooner the person with AD and family know, the more time they have to make future living arrangements, handle financial matters, establish a durable power of attorney, deal with other legal issues, create a support network, or even make plans to join a research study. Being able to participate for as long as possible in making decisions about the present and future is important to many people with AD.

Finally, scientists also see advantages to early diagnosis. Developing tests that can reveal what is happening in the brain in the early stages of Alzheimer's disease will help them understand more about the cause and development of the disease. It will also help scientists learn when and how to start drugs and other treatments so that they can be most effective.

Scientists are now exploring ways to help physicians diagnose AD earlier and more accurately. For example, some studies are focusing on changes in personality and mental functioning. These changes can be measured through memory and recall tests. Tests that measure a person's abilities in areas such as abstract thinking, planning, and language can also help pinpoint changes in function. Researchers are working hard to improve these standardized tests so that they can better track the changes that might point to early AD or predict which individuals are at higher risk of developing AD in the future.

Other studies are examining the relationship between early damage to brain tissue and outward clinical signs. Still others are looking for changes in blood chemistry that might indicate the progression of Alzheimer's disease.

One of the most exciting areas of ongoing research in this area is neuroimaging. Over the last decade, scientists have developed several highly sophisticated imaging systems that have been used in many areas of medicine, including Alzheimer's disease. Positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI) are all examples. These "windows" on the living brain can help scientists measure the earliest changes in brain function or structure in order to identify those people who are at the very first stages of the disease - even before they develop signs and symptoms.

These types of scans are still primarily research tools, but one day, neuroimaging might be used more commonly to help physicians diagnose AD early. These tools may even be used someday to monitor the progress of the disease and assess patient responses to drug treatment.

Back to Top

The Human Side of AD Research

The Religious Orders Study and the Nun Study: Lives of Service Continue Even After Death

One way that scientists have tried to unravel the mystery of AD and other complex diseases, like heart disease or cancer, is to compare the characteristics, lifestyles, and disease rates of different groups of people. This approach has often provided clues as to why some people get a disease and others don't.

Another way is to study one group of people over time. The notion here is that data gathered over a period of years will reveal important clues about the origins of the disease under investigation. The knowledge gained also may lay the foundation for future treatment or prevention strategies. The Framingham Heart Study is one famous example of this kind of study. It has followed two generations of Massachusetts residents for 50 years, and its findings have revolutionized the way we think about, treat, and prevent heart disease.

The National Institute on Aging is funding two Alzheimer's disease studies that are using this approach - but with a unique twist. These studies involve members of religious communities.

Since 1990, scientists have been working with more than 650 nuns of the School Sisters of Notre Dame, who are located in various parts of the U.S. The Nun Study is an expansion of a pilot project begun in 1986 with a School Sisters of Notre Dame convent in Mankato, Minnesota.

Since 1993, scientists have also been investigating the mental and physical capacities of older nuns, priests, and brothers in the Religious Orders Study. More than 30 religious communities in a dozen States are participating in this study.

All of the participants in both studies agree to have detailed physical and mental function exams every year. Volunteers may spend decades in the study, repeating the tests each year. These exams help researchers better understand the effects on the brain of aging, AD, and other disorders. Participants also agree to donate their brains to the study when they die. This allows the investigators to match many years' worth of clinical and psychological information with the results of examinations of after-death brain tissue. These volunteers consider participating in these studies a wonderful chance to continue their lives of service to others. As one participant in the Nun Study put it, "[They] can have my brain. What good is it going to do me when I'm six
feet under?"

The large numbers enrolled in the study ensure that some volunteers will still have normal brain function at the time of death. Others will have developed the clinical signs of AD. Still others will have other neurological disorders, such as Parkinson's disease. The yearly examinations enable researchers to detect signs of AD among participants and to track, year by year, the progress and treatment of the disease among those who develop it.

But why work with religious orders? What's special about them? One reason why members of religious orders are good study participants is that they often live together and have similar lifestyles, educational levels, daily routines, and activities. This cuts down on the variations among participants that make it difficult for scientists to interpret research results. It also makes it easy for study staff to keep track of volunteers over time and to maintain complete information on them.

Working with these participants has allowed the research teams to explore several exciting ideas. For example, the Religious Orders Study team recently worked with their participants to examine a "use-it-or-lose-it" brainpower hypothesis. At an initial evaluation, the researchers asked more than 700 priests and nuns about the amount of time they spent in seven common activities that involve significant information processing - watching television; listening to the radio; reading newspapers or magazines; reading books; playing cards, checkers, and puzzle games; and going to museums. After tracking the participants for 4 1/2 years, the researchers found that, on average, the risk of developing AD was 47 percent lower in those who did these activities most frequently than in those who did them least frequently. The reasons for this finding aren't entirely clear yet, but it may be that mentally stimulating activities protect the brain in some way. Or, perhaps some other mechanism may be at work that strengthens information processing skills to compensate for age-related declines in other cognitive areas.

The Nun Study has one particularly rich treasure trove to work with - the autobiographies written by the nuns when they entered the order. These personal records provide basic information on the nuns' early lives and families and are an objective measure of each woman's ability to think, remember, and present ideas in writing. Study investigators have found a fascinating link between their early writing skills and later cognitive abilities. The researchers performed an analysis of the autobiographies to determine the grammatical complexity and the "density" of ideas in each. They then examined brain tissue from nuns who had died. The investigators found that most of the nuns whose brain tissue showed significant signs of AD had written autobiographies with low grammatical complexity and idea density. Though the reasons for this link aren't fully understood, a higher linguistic ability early in life may provide some protection against the influences that lead to AD.

Causes of Dementia
Dementia is the loss of cognitive functioning - thinking, remembering, and reasoning - to such an extent that it interferes with a person's daily life and activities. It is not a disease itself, but a group of symptoms that often accompanies a disease or condition. Some dementias are treatable or curable; others are less responsive to treatment.

Back to Top

Current Tools For Diagnosing AD

A definitive diagnosis of Alzheimer's disease is still only possible after death, during an autopsy, when the plaques and tangles can actually be seen. But with the tools now available, experienced physicians can be pretty confident about making an accurate diagnosis in a living person. Here's how they do it.

They take a detailed patient history, including:

• A description of how and when symptoms developed
• A description of the patient's and his or her family's overall medical condition and history
• An assessment of the patient's emotional state and living environment

They get information from family members or close friends:

• People close to the patient can provide valuable insights into how behavior and personality have changed; many times, family and friends know something is wrong even before changes are
  evident on tests.

They conduct physical and neurological examinations and laboratory tests:

• Blood and other medical tests help determine neurological functioning and identify possible non-AD causes of dementia.

They do a computerized tomography (CT) scan or a magnetic resonance imaging (MRI) test:

• Brain scans like these can detect strokes or tumors or can reveal changes in the brain's structure and function that indicate early AD.

They conduct neuropsychological testing:

• Q&A tests or other tasks that measure memory, language skills, ability to do arithmetic, and other abilities related to brain functioning help indicate what kind of cognitive changes are occurring.

Criteria for "Probable" Alzheimer's Disease

Because no simple and reliable biological test for AD is available, the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Association together established criteria to help physicians diagnose AD. These criteria also help physicians distinguish between AD and other forms of dementia. "Probable" Alzheimer's disease is determined when a person has:

• Dementia confirmed by clinical and neuropsychological examination
• Progressive worsening of memory and other mental functioning
• No disturbances of consciousness (no "blacking out")
• Symptoms beginning between ages 40 and 90
• No other disorders that might account for the dementia

As they get older, some people develop a memory deficit greater than that expected for their age. However, other aspects of cognition are not affected, so these people do not meet all the accepted criteria for AD. Thus, they are said to have "mild cognitive impairment" (MCI). About 40 percent of these individuals will develop AD within 3 years. Others, however, do not seem to progress to AD, at least in the time frame studied thus far (up to approximately 6 years). Understanding more about the characteristics and development of MCI is essential in helping clinicians diagnose early stages of AD.

Back to Top

<< Back | Next >>