PET Imaging Reveals Cognitive Impairment Predicted from Plaques

Molecular brain imaging using a radioactive dye has been found to identify early evidence of Alzheimer’s disease (AD) that may predict future cognitive decline among adults with mild or no cognitive impairment, according to a 36-month follow-up study. A biomarker such as this could effectively identify those at greatest risk for cognitive decline, thus helping clinicians better assess and treat patients, while also fast-tracking the testing of drugs to treat the disease.

The US multicenter study confirms earlier findings suggesting that identifying silent beta-amyloid plaque build-up in the brain could help guide care and treatment decisions for patients at risk for AD. The findings appeared online March 11, 2014, in Molecular Psychiatry, a Nature Publishing Group journal. “Our research found that healthy adults and those with mild memory loss who have a positive scan for these plaques have a much faster rate of decline on memory, language and reasoning over three years,” said lead author P. Murali Doraiswamy, MD, professor of psychiatry and director of the neurocognitive disorders program at Duke University (Durham, NC, USA) Medical Center.

Earlier research has found that in patients with AD changes in the brain start years, perhaps decades, before cognitive symptoms emerge. The current study, which comprised of 152 adults ages 50 and older, was designed to evaluate whether silent pathologic alterations in the brain associated with AD and identified with positron emission tomography (PET) imaging can predict cognitive decline. Of the participants, 69 had normal cognitive function at the start of the study, 52 had been recently diagnosed with mild cognitive impairment, and 31 were diagnosed with AD.

Study participants completed cognitive tests and underwent PET scanning of their brains. This type of imaging uses a radioactive tracer to look for chemical signs of disease in specific tissues.

The radioactive dye used, florbetapir (Amyvid), was approved by the US Food and Drug Administration (FDA) in 2012 for PET imaging of the brain to estimate beta-amyloid plaque density in patients being evaluated for cognitive impairment. It binds to the beta-amyloid plaques that characterize AD, helping to gauge the degree to which plaques have formed in different brain regions. Using this information, the researchers rated the PET scans as positive or negative.

After 36 months, the researchers repeated the same cognitive exams to reassess participants. They found that those with mild or no cognitive impairment who had evidence of plaques at the study’s start, declined to a greater degree on cognitive tests than those with negative scans.

Thirty-five percent of plaque-positive participants who started with mild cognitive impairment progressed to AD, compared to 10% without plaque. Moreover, plaque-positive study participants with mild impairment were more than twice as likely to be given cognition-enhancing drugs as those without plaque were.

On the other hand, those with negative scans experienced much less decline: 90% of participants with mild cognitive impairment but no plaque did not progress to AD. This finding supports the negative predictive value (NPV) of using PET imaging to identify patients not apt to decline, which has significant implications for both clinical research and treatment. “Having a negative scan could reassure people that they are not likely to be at risk for progression in the near future,” Dr. Doraiswamy said.

Dr. Doraiswamy emphasized, however, that florbetapir is currently not approved to predict the development of dementia and is not used as a screening approach in cognitively healthy individuals. Future longitudinal studies are required additionally to determine the prognostic role of beta-amyloid plaque PET imaging in a clinical environment. “Even though our study suggests the test has predictive value in normal adults, we still need additional evidence,” Dr. Doraiswamy said. “We need longer-term studies to look at the consequences of silent brain plaque build-up, given that it affects 15%–30% of normal older people.”

Dr. Doraiswamy noted that the findings provide support for planned and ongoing multicenter clinical trials of asymptomatic older adults with plaque-positive scans. The research also has implications for other disorders where amyloid might have a role, such as traumatic brain injury situations.

The study was funded by Eli Lilly/Avid Radiopharmaceuticals (Philadelphia, PA, USA), which markets florbetapir, and was conducted by Avid and the AV45-A11 study group, a consortium of Alzheimer’s clinical research centers.

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