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PET May Predict Alzheimer’s Decline

PET imaging using the radiotracer 18F-FDDNP can track and predict cognitive decline over a two-year period, according to a report in the February issue of Archives of Neurology.

Researchers at UCLA developed 18F-FDDNP, which binds to both plaque and tangle deposits—the hallmarks of Alzheimer's disease—and can be imaged using PET, to show where in the brain these abnormal protein deposits are accumulating. Study author Gary Small, MD, a professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA, says FDDNP-PET scanning is the only available brain-imaging technique that can assess tau tangles. Autopsy findings have found that tangles correlate with Alzheimer's disease progression much better than do plaques.

“We are finding that this may be a useful neuroimaging marker that can detect changes early, before symptoms appear, and it may be helpful in tracking changes in the brain over time,” Small says. The next step in research will involve a longer duration of follow-up with larger numbers of patients to confirm the small study’s results.

For the initial study, researchers performed brain scans and cognitive assessments on the subjects at baseline and then again two years later. The study involved 43 volunteer participants with an average age of 64 who did not have dementia. At the start of the study, approximately one-half (22) of the participants had normal brain aging and the other one-half (21) had mild cognitive impairment (MCI), a condition that increases a person's risk of developing Alzheimer's disease.

Researchers found that for both groups, increases in FDDNP binding in the frontal, posterior cingulated, and global areas of the brain at the two-year follow-up correlated with the progression of cognitive decline. These areas of the brain are involved in decision making, complex reasoning, memory, and emotions. Higher initial baseline FDDNP binding in both subject groups was associated with a decline in cognitive functioning in areas such as language and attention at the two-year follow-up.

“We found that increases in FDDNP binding in key brain areas correlated with increases in clinical symptoms over time,” says study author Jorge R. Barrio, PhD. “Initial binding levels were also predictive of future cognitive decline.”

Among the subjects with mild cognitive impairment, the level of initial binding in the frontal and parietal areas of the brain provided the greatest accuracy in identifying those who developed Alzheimer’s disease after two years. Of the 21 subjects with MCI, six were diagnosed with Alzheimer's at follow-up, and these six subjects had higher initial frontal and parietal binding values than the other subjects in the MCI group.

In the normal aging subjects, three developed MCI after two years. Two of these three participants had had the highest baseline binding values in the temporal, parietal, and frontal brain regions among this group.

Small recently received research approval from the FDA to use FDDNP-PET to study people with mild cognitive impairment to determine whether a high-potency form of curcumin—a spice with antiamyloid, antitau, and anti-inflammatory properties—can prevent Alzheimer's disease and the accumulation of plaques and tangles in the brain.

— Jim Knaub is editor of Radiology Today.