Florbetapir-PET links beta amyloid to cognitive decline at 3 years

Individuals who tested positive for beta amyloid on florbetapir-PET brain scans were more likely to decline cognitively over a three-year period than those with a negative scan, in a study published online March 11 in Molecular Psychiatry.

In addition, 14% of subjects who were deemed cognitively normal at the start of the study tested positive for beta-amyloid deposits and showed some decline in cognitive abilities.

"Our study shows that those 14% progressed at a much faster rate than the rest of the people who were [beta-amyloid] negative," lead author Dr. P. Murali Doraiswamy, professor of psychiatry and director of the neurocognitive disorders program at Duke Medicine, told AuntMinnie.com. "Of course, our results are early, so we need larger studies of more normal people."

The findings further support research by Doraiswamy and colleagues published in 2012, in which subjects who had positive beta-amyloid florbetapir-PET scans showed a greater decline in memory after 18 months than individuals with negative scans (Neurology, October 16, 2012, Vol. 79:16, pp. 1636-1644).

Other studies have also shown that certain people progress more quickly toward cognitive decline, dementia, and Alzheimer's disease than others.

"So there is huge interest in trying to find out which tests can offer a high degree of prediction for future cognitive decline," Doraiswamy said. "If we can accurately identify individuals who are likely to progress compared to individuals who are not likely to progress, that can help drug discovery, even though we don't have a treatment right now to prevent Alzheimer's."

Beta-amyloid effect

Florbetapir is a PET imaging agent that specifically binds to beta amyloid, which has been linked with the onset of Alzheimer's disease and other forms of cognitive impairment. It is marketed under the trade name Amyvid in the U.S. and Europe by Eli Lilly and its subsidiary Avid Radiopharmaceuticals.

"Previously, the only way you could test if someone had beta-amyloid plaque in the brain was at autopsy," Doraiswamy explained. "With this [florbetapir] PET scan, we can tell whether or not someone has significant plaque buildup in the brain."

The new multicenter, prospective study enrolled 152 adults 50 years of age and older to assess pathological changes in the brain through florbetapir-PET imaging and whether those changes could predict cognitive decline (Molecular Psychiatry, March 11, 2014).

Of the participants, 69 had normal cognitive function at the start of the study, 52 had recently been diagnosed with mild cognitive impairment, and 31 had been diagnosed with Alzheimer's disease.

Subjects completed cognitive tests at the beginning of the study and also received florbetapir-PET scans (Discovery LS PET/CT and Advance PET, GE Healthcare; ECAT HR+ and Biograph PET/CT, Siemens Healthcare). Imaging was performed 50 minutes after intravenous injection of 10 mCi (370 MBq) of florbetapir.

"Then we followed individuals over time using cognitive tests," Doraiswamy said. "We tested as to whether or not a baseline scan could predict which subjects would decline faster in their cognition and which subjects would go on to develop Alzheimer's."

Positive PET results

Based on the florbetapir-PET scans, 10 (14%) of the 69 cognitively normal individuals were positive for beta amyloid. In addition, 19 (37%) of the 52 subjects with mild cognitive impairment and 21 (68%) of the 31 individuals with Alzheimer's tested positive.

Further analysis showed that 35% of plaque-positive participants who started with mild cognitive impairment had progressed to Alzheimer's at 36 months, compared with 10% without beta-amyloid plaque.

Conversely, 90% of participants with mild cognitive impairment and no plaque did not progress to Alzheimer's. "That suggests that a negative scan has what we call negative predictive value," Doraiswamy added. "We found that the negative predictive value was 90%."

"What we found is that regardless of a baseline memory status -- whether you were normal at baseline, whether you were minimally impaired, or you had Alzheimer's -- [individuals] with a positive scan decline faster over the next three years compared to those who had a negative scan," he said.

The study results indicate that PET imaging of beta amyloid in cognitively normal individuals and those with mild cognitive impairment could help predict their future risk of cognitive decline, the authors concluded. The findings also support the negative predictive value of the technique for identifying patients unlikely to decline.

Doraiswamy did caution, however, that florbetapir is not currently approved to predict the development of dementia and is not used as a screening tool in cognitively normal people. Future longitudinal studies are needed to further clarify the prognostic role of beta-amyloid plaque PET imaging in a clinical setting.

"Even though our study suggests the test has predictive value in normal adults, we still need additional evidence," he said in a statement. "We need longer-term studies to look at the consequences of silent brain plaque buildup, given that it affects 15% to 30% of normal older people."

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