Brain imaging using radioactive dye can detect early evidence of Alzheimer's disease that may predict future cognitive decline among adults with mild or no cognitive impairment, according to a 36-month follow-up study led by Duke Medicine.
The national, 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 Alzheimer's. 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, M.D., professor of psychiatry and director of the neurocognitive disorders program at Duke.
Alzheimer's disease – which currently has no cure – afflicts an estimated five million U.S. adults, and is the sixth-leading cause of death among adults, according to the Centers for Disease Control and Prevention. Prior studies have found that changes in the brain begin years, and possibly decades, before cognitive symptoms emerge.
A biomarker that could accurately identify those at greatest risk for cognitive decline could help clinicians better evaluate and treat patients, while also accelerating the testing of drugs to treat the disease.
The current study, which enrolled 152 adults ages 50 and older, was designed to assess whether silent pathological changes in the brain associated with Alzheimer's and detected with positron emission tomography (PET) 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 Alzheimer's disease.
Subjects completed cognitive tests and underwent PET scans 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 U.S. Food and Drug Administration 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 Alzheimer's disease, helping to measure the extent 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 trial's start worsened 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 Alzheimer's, compared to 10 percent without plaque. In addition, plaque-positive participants with mild impairment were more than twice as likely to be started on cognitive-enhancing medication than those without plaque.
Conversely, those with negative scans experienced much less decline: 90 percent of participants with mild cognitive impairment but no plaque did not progress to Alzheimer's. This finding supports the negative predictive value of using PET imaging to identify patients unlikely to decline, which has important 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," Doraiswamy said.
Doraiswamy cautioned that florbetapir is currently not 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," Doraiswamy said. "We need longer-term studies to look at the consequences of silent brain plaque build-up, given that it affects 15 to 30 percent of normal older people."
Doraiswamy added 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 conditions where amyloid might play a role, such as traumatic brain injury (from sports or combat).
In addition to Doraiswamy, study authors include Terence Z. Wong of Duke (currently at the University of North Carolina at Chapel Hill); Reisa A. Sperling and Keith Johnson of Massachusetts General Hospital, Harvard Medical School; Eric M. Reiman of Banner Alzheimer's Institute; Marwan N. Sabbagh of Banner-Sun Health Research Institute; Carl H. Sadowsky of Nova SE University; Michael Grundman of Global R&D Partners and the University of California, San Diego; Adam S. Fleisher of Banner Alzheimer's Institute and the University of California, San Diego; and Alan Carpenter, Abhinay D. Joshi, Ming Lu, Mark A. Mintun, Daniel M. Skovronsky and Michael J. Pontecorvo of Avid Radiopharmaceuticals.
The study was funded by Eli Lilly/Avid Radiopharmaceuticals, which markets florbetapir, and was conducted by Avid and the AV45-A11 study group, a consortium of Alzheimer's clinical research centers. Doraiswamy receives advisory and speaker fees from Lilly/Avid, as well as other companies. A full list of author disclosures can be found in the manuscript.
Rachel Harrison | EurekAlert!
Real-time imaging of lung lesions during surgery helps localize tumors and improve precision
30.07.2015 | American Association for Thoracic Surgery
Experimental MERS vaccine shows promise in animal studies
29.07.2015 | NIH/National Institute of Allergy and Infectious Diseases
Physicists from Regensburg and Marburg, Germany have succeeded in taking a slow-motion movie of speeding electrons in a solid driven by a strong light wave. In the process, they have unraveled a novel quantum phenomenon, which will be reported in the forthcoming edition of Nature.
The advent of ever faster electronics featuring clock rates up to the multiple-gigahertz range has revolutionized our day-to-day life. Researchers and...
Researchers have developed an ultrafast light-emitting device that can flip on and off 90 billion times a second and could form the basis of optical computing.
Joint BioEnergy Institute study identifies bacterial protein that is key to protecting rice against bacterial blight
A bacterial signal that when recognized by rice plants enables the plants to resist a devastating blight disease has been identified by a multi-national team...
Researchers in the Cockrell School of Engineering at The University of Texas at Austin are one step closer to delivering smart windows with a new level of energy efficiency, engineering materials that allow windows to reveal light without transferring heat and, conversely, to block light while allowing heat transmission, as described in two new research papers.
By allowing indoor occupants to more precisely control the energy and sunlight passing through a window, the new materials could significantly reduce costs for...
Argonne scientists used Mira to identify and improve a new mechanism for eliminating friction, which fed into the development of a hybrid material that exhibited superlubricity at the macroscale for the first time. Argonne Leadership Computing Facility (ALCF) researchers helped enable the groundbreaking simulations by overcoming a performance bottleneck that doubled the speed of the team's code.
While reviewing the simulation results of a promising new lubricant material, Argonne researcher Sanket Deshmukh stumbled upon a phenomenon that had never been...
23.07.2015 | Event News
10.07.2015 | Event News
25.06.2015 | Event News
30.07.2015 | Life Sciences
30.07.2015 | Trade Fair News
30.07.2015 | Awards Funding