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.