For the first time in 27 years, revised criteria for the clinical diagnosis of Alzheimer’s disease have been published, along with a new research agenda for studying the earliest stages of the disease, before symptoms appear.

Three expert workgroups spearheaded by the National Institute on Aging and the Alzheimer’s Association published their guidelines for clinicians and recommended research priorities in a series of articles available online April 19 and in the May 2011 print issue of Alzheimer’s & Dementia, the journal of the Alzheimer’s Association.

The guidelines mark a significant change in how experts think about and study Alzheimer’s, said Dr. Denise Park, co-director of UT Dallas’ Center for Vital Longevity, who served on the 21-member international workgroup responsible for laying out the new research agenda.

Park and other scientists are studying the complex processes in the brain that ultimately lead to the cognitive decline associated with Alzheimer’s disease, which recent studies suggest might begin many years—perhaps even decades—before symptoms of the disease occur or before diagnosis.

A more complete scientific understanding of how Alzheimer’s disease progresses in these earliest, or “preclinical” stages will help in the development of earlier interventions, according to the panel’s report.

“We’re not yet to the point where we can effectively intervene in the progression of Alzheimer’s disease,” said Park, the Distinguished University Chair in Brain and Behavioral Sciences and a Regents’ Research Scholar at UT Dallas. “But this report is a blueprint for scientists to better define the disease at its earliest stages, before symptoms appear and when there is potential for interventions to do the most good.”

The panel’s recommendations include a new focus on studying individuals in the preclinical phase — those who do not yet experience characteristic Alzheimer’s symptoms such as memory loss — yet who exhibit certain so-called biomarkers that can indicate a risk of later developing the disease.

One of those biomarkers is the buildup of a protein called amyloid on the brain, which currently plays a critical role in the diagnosis of Alzheimer’s. Until recently, however, amyloid could only be definitively detected at autopsy. New radiotracer substances that latch on to amyloid deposits now allow researchers to see amyloid plaques in the living human brain by way of positron emission tomography, or PET scan.

Park and other researchers are using this advanced imaging technique to investigate whether the presence of amyloid in otherwise healthy people without symptoms of Alzheimer’s can predict who is most at risk for developing the disease later on in life.

“It’s not at all clear whether the presence of amyloid alone condemns an individual to Alzheimer’s,” Park said. “Nor do we know whether relative small amounts of amyloid predict a better outcome. There are other factors that also can influence how well someone ages cognitively, and we and others are currently studying many of these factors systematically.” In the Dallas Lifespan Brain Study, for example, Park and her colleagues at UT Dallas and UT Southwestern Medical Center are investigating why some people with “unhealthy” brains function well while others don’t, in an effort to understand both healthy and unhealthy aging.

One of the challenges for scientists, Park said, is to more firmly link the presence of specific pathological changes and biomarkers in people who do not show symptoms of Alzheimer’s with the subsequent emergence of impairments that can be measured clinically.

This challenge is similar to that faced by researchers and clinicians who, decades ago, first conducted studies aimed at identifying risk factors that can contribute to heart disease, and then determined which patients were most likely to benefit from medical and/or lifestyle intervention.

Just as treatments now are widely available for high cholesterol and high blood pressure — both clinically measurable biomarkers that contribute to the development of heart disease — it may be that individuals with early  indications of potential Alzheimer’s could optimally be treated before significant symptoms, such as cognitive impairment and memory loss, develop, Park said.