The use of positron emission tomography (PET) imaging may help identify findings in brain tissue associated with Alzheimer's disease (AD), according to two articles published Online First in the Archives of Neurology, one of the JAMA/Archives journals.

As scientists seek to understand more about AD and other forms of dementia, they are exploring the use of PET, according to background information in the article. This imaging technique involves the use of radioactive tracers to highlight areas of the brain affected by these conditions. Various teams of researchers are studying the effectiveness of different types of tracers for identifying brain findings associated with these conditions.

In one study, David A. Wolk, M.D., from the Penn Memory Center in Philadelphia, and colleagues, evaluated use of a tracer called fluorine 18-labeled flutemetamol for imaging the brain. The study involved conducting PET scans on seven patients who were given a dose of this substance. All had previously undergone a biopsy for normal pressure hydrocephalus, a progressive condition that includes dementia and can be difficult to distinguish from AD. Researchers found correspondence between readings of the PET scans and evidence of amyloid lesions-the plaque associated with AD-provided by microscopic evaluation of the biopsied tissue.

In another study, Adam S. Fleisher, M.D., from Banner Alzheimer's Institute in Phoenix, and colleagues, evaluated PET imaging using the tracer florbetapir F 18. The study population included 68 individuals with probable AD, 60 individuals with mild cognitive impairment, and 82 healthy individuals who served as controls. PET scanning was used to monitor activity of the agent being studied. These researchers found differences in the brain uptake of florbetapir F 18, between the three groups, and in the detection of amyloid plaque; the differences may be large enough to help distinguish between the conditions, and between impaired versus unimpaired brains.

The authors of both articles suggest that their results may demonstrate ways in which PET imaging can be used with selected tracers to help identify findings associated with AD. "With the potential emergence of disease-specific interventions for AD," state Wolk et al, "biomarkers that provide molecular specificity will likely become of greater importance in the differential diagnosis of cognitive impairment in older adults." Indeed, Fleisher et al write, "Amyloid imaging offers great promise to facilitate the evaluation of patients in a clinical setting."

Dr. Wolk's study was entirely sponsored by GE Healthcare. Dr. Fleisher's study was supported by funding from Avid Radiopharmaceuticals, a wholly owned subsidiary of Eli Lilly.

In an editorial accompanying the papers, William J. Jagust, M.D., from the Helen Wills Neuroscience Institute at the University of California, Berkeley, comments on the role of amyloid in AD and the detection of this plaque as "a topic of active investigation." The articles by Wolk et al and Fleisher et al, he suggests, "continue to advance the field."

Jagust notes that the study by Fleisher et al attempted to define cutoffs for positive or negative presence of amyloid. "Most clinical imaging methods rely on interpretation, not quantitation," he states. "Nevertheless, quantitation of these scans has considerable value because it provides a reliable measure that can be compared across laboratories on either a continuous or dichotomous level."

Jagust also discusses the problem of how to treat "borderline" or "intermediate" results. He notes that the study by Wolk et al found "perfect agreement" between the scans and the biopsied tissue in terms of positive or negative ratings.

Further, Jagust adds, the two studies show that cutoff levels may be distinct from agent to agent. "These are likely to be related to differences in the tracer as well as to differences in the methods already noted," he says. Nevertheless, points out Jagust, "Another interesting point is how exceptionally well all of these tracers perform in comparison to pathology."

Dr. Jagust has served as a consultant to GE Healthcare, which manufactures flutemetamol, and collaborates with Avid Radiopharmaceuticals, which manufactures florbetapir, through the Alzheimer's Disease Neuroimaging Initiative.