A negative florbetaben PET scan provides solid evidence to rule out amyloid pathology in the brain based on phase III trial data matched by histopathology. The research was presented Wednesday during the Emerging Sciences session of the American Academy of Neurology (AAN) annual meeting in Philadelphia.
Marwan N. Sabbagh, MD, director of Banner Sun Health Research Institute and research professor of neurology at the University of Arizona College of Medicine-Phoenix, and colleagues presented their research from the largest amyloid study to date. The data confirm the sensitivity of F-18 florbetaben (Neuraceq) for detecting neuritic beta-amyloid deposition in the brain when compared to autopsied brains of those who had been tested.
“These data will ensure that a negative amyloid imaging scan with florbetaben lowers the probability of amyloid, and by extension, Alzheimer’s disease as a contributor to the dementia,” Sabbagh told Molecular Imaging in an exclusive interview.
For this study, three independent readers interpreted florbetaben PET scans from 74 end-of-life patients, including 57 subjects with Alzheimer’s disease, three with dementia with Lewy bodies, six with other dementias and eight without dementia. By the end of the study, all had undergone an autopsy of the brain to confirm neuropathology and compared with previous PET assessment with florbetaben.
Results showed proof-positive evidence of beta-amyloid by histopathology in 47 of the subjects, including 44 of the 57 with Alzheimer’s disease. Histopathology showed signs of amyloid plaque in one of three dementia with Lewy body patients, one of six of the patients with other dementias and one out of the eight patients with no dementia diagnosis. Positive florbetaben PET scans were interpreted correctly in 46 out of 47 cases. Amyloid was not found in 27 subjects. Of these, 23 had non-Alzheimer’s neurodegeneration including frontotemporal dementia and Parkinson’s, and four showed no sign of neurodegenerative pathology.
“The negative predictive values aids in excluding Alzheimer’s disease as a contributor and reinforces the approved label,” he added.
Overall sensitivity was gauged at 97. 9 percent and specificity at 88.9 percent. Negative predictive value of a florbetaben PET scan was deemed to be 96 percent.
“Amyloid imaging could become one of the tests of choice in the diagnosis of AD [Alzheimer’s disease] and could reduce the delay in treatment by reducing the diagnostic uncertainty,” noted Sabbagh. “A negative scan should encourage the physician to search for other causes of cognitive decline and tailor available treatment options.”
This convincing data do not mean that the clinical use of florbetaben will change overnight. Even though three amyloid imaging agents are now approved by the FDA, including Neuraceq, Vizamyl and Amyvid, Centers for Medicare & Medicaid Services (CMS) reimbursement for amyloid imaging is limited under coverage with evidence development.
“CMS cites the need to establish relevance and added value for clinical utility,” Sabbagh remarked. “I as a dementia neurologist have ordered amyloid imaging and it informed me about the potential for the diagnosis and guiding care, decision making and treatment.”
Only time will tell if amyloid imaging will pick up and be fully supported by payers in order to determine whether an aging population is positive for Alzheimer’s and other neurodegenerative diseases.