In two cases of progressing dementia, PET imaging with amyloid and tau tracers helped to clarify the diagnosis by ruling out Alzheimer’s disease, researchers suggested.

Case 1 was a 71-year-old former NFL player who had experienced numerous concussions during his career and was developing what appeared clinically to be Alzheimer’s disease. However, PET scanning with the [18F]-florbetapir tracer showed no evidence of cerebral amyloid plaques, which excluded Alzheimer’s, according to Samuel Gandy, MD, of the Icahn School of Medicine at Mount Sinai in New York, and colleagues.

Case 2 was a 59-year-old physician who had suffered a head injury skiing, but who also had shown personality, mood, and cognitive changes in the months before the injury. Amyloid imaging with [18F]-florbetapir PET was negative except for at the site of the head injury, and the diagnosis of Alzheimer’s disease (AD) was therefore ruled out, the researchers reported online in Translational Psychiatry.

A Work in Progress

“Three new positron emission tomography tracers have been approved recently by the U.S. Food and Drug Administration as clinical tools to estimate brain amyloid burden in patients being evaluated for cognitive impairment or dementia,” and “several new PET imaging neurotracers have been developed that detect pathological tau in vivo,” Gandy and colleagues wrote.

“Our data suggest that PET imaging using the [18F]-T807 tau tracer is an effective method of diagnosing or ruling out chronic traumatic encephalopathy (CTE) in a living brain,” said Gandy. “Until now, CTE diagnosis has only been possible by evaluating postmortem brain tissue,” Mount Sinai stated in a press release.

Robert Cantu, MD, who is co-director of the chronic traumatic encephalopathy (CTE) research group studying former NFL players at Boston University said that he and his colleagues have been using the [18F]-T807 tracer for tau in their traumatic brain injury (TBI) evaluations, and that “it has great theoretical benefit. It’s specific for tau and that’s what you want” for diagnosing CTE.

Other types of tracers detect both tau and amyloid, so don’t distinguish between Alzheimer’s disease and CTE, but the T807 tracer picks up only tau, “so it could be the Holy Grail” for CTE, Cantu told MedPage Today.

“But the problem right now is that this tracer doesn’t provide sharp, highly defined images, so it’s difficult to see exactly where the tau is deposited,” he said.

This is important because the sites of deposition of tau differ in CTE and Alzheimer’s disease, he explained. In CTE, the deposition is in the superficial layers of the cortex, at the depths of sulci, and around blood vessels, while in Alzheimer’s tau is found in the deeper layers of the cortex. “Location is everything,” he said.

“If this PET tracer were sharp enough to show that the tau is at the depths of the sulci or around the blood vessels, everybody would say this is it — this is the Holy Grail,” Cantu said.

But it’s still a “work in progress,” he said.

Case 1

The patient was evaluated by the NFL Neurological Care Program team at Mount Sinai. He had been taking donepezil and memantine, with no apparent benefit, and was hoping to enroll in a clinical trial of an amyloid-lowering drug.

He underwent neuropsychological testing, which revealed multiple areas of impairment, including verbal comprehension and recall, fine motor functioning, and information processing.

Following this evaluation, the experts could not agree on whether the patient had Alzheimer’s disease along with his probable post-traumatic encephalopathy, so he was referred for [18F]-florbetapir PET imaging. The scan identified few or no fibrillar amyloid plaques.

“This case illustrates the potential for brain amyloid imaging to clarify diagnosis and to prevent inappropriate treatment,” the researchers wrote, noting that the negative scan excluded him from clinical trials of amyloid-lowering therapy.

He also underwent [18F]-T807 imaging, which identified signals primarily in the globus pallidus and substantia nigra, results that were “somewhat unexpected,” and not what is usually seen in CTE.

Rather, this pattern was more suggestive of progressive supranuclear palsy, but the patient didn’t have the typical clinical findings associated with that disorder.

The researchers noted that a few other cases have been reported in which CTE was identified in conjunction with supranuclear palsy, and suggested that this may represent an unusual phenotype of CTE with subcortical tauopathy.

“Indeed, the neuroimaging of CTE may lead to expansion and/or revision of the definition and staging of CTE beyond the current pathology-based system,” they stated.

Case 2

The patient’s injury resulted from falling off a ski lift and hitting his head on concrete, after which he developed headaches and weakness and numbness in one hand. An MRI revealed a subdural hematoma, and he underwent craniotomy.

His personality and cognitive changes prior to the fall included loss of short term memory, agitation, and depression.

He was referred for neurologic and neuropsychological evaluations at the Mount Sinai Alzheimer’s Disease Research Center, where he underwent imaging with [18F]-florbetapir and [18F]-fluorodeoxyglucose scans.

The [18 F]-fluorodeoxyglucose scan revealed “decreased metabolism in the medial portions of the frontal lobes, more pronounced in the left side than the right, and the posterior portion of the left temporal lobe,” the researchers reported.

The [18 F]-florbetapir scan found little evidence of amyloid except in the region of the TVI. The patient ultimately was diagnosed with frontotemporal lobar degeneration, according to the Mount Sinai researchers.

“His clinical features showed a frontotemporal type of dementia that was clearly supported by the [18F]-fluorodeoxyglucose scan,” said Roger Kelley, MD, who chairs the department of neurology at Tulane University in New Orleans.

“So he didn’t necessarily need the amyloid scan, although it did help exclude Alzheimer’s disease. But the question is, would it affect management?” Kelley said in an interview.

“At this point, probably not, because we would be likely to try treatment with donepezil and memantine anyway,” he said.

The Future

“The amyloid and tau scans are really research tools at present, not for use in the clinical realm, but with further refinement may have benefit for use in rigorous clinical trials,” said Kelley, who was not involved in the study.

The number of published cases also remains small. For instance, one study from the University of California Los Angeles included five former players. The tracer used in that study, known as [18F]-FDDNP, “has been around for a long time and is not specific for tau. It also picks up beta-amyloid, so it couldn’t distinguish between Alzheimer’s and CTE,” Cantu said.

John Trojanowski, MD, PhD, of the Center for Neurodegenerative Disease Research at the University of Pennsylvania noted that the sparsity of cases is “a major drawback of TBI research now.” However, he provided MedPage Today with information about the Department of Defense’s Alzheimer’s Disease Neuroimaging Initiative, saying that the studies being undertaken hopefully “will rectify this.”

The project summary provides an overview of the initiative, which intends to identify Vietnam veterans who experienced TBI and to assess their cognitive abilities and perform amyloid PET imaging. It’s a multisite project being funded by the National Institute on Aging, with an overall goal of “validation of imaging and biomarkers for AD clinical trials” and ultimately “to prevent AD in combat veterans.”

“This project is an important step in that direction because it will identify risk factors for development of AD in military veterans and will provide information and a network of sites for design, statistical powering, and performance of clinical treatment and prevention trials in the future.”

The authors disclosed no financial relationships.



Primary source: Translational Psychiatry
Source reference: Mitsis E, et al “Tauopathy PET and amyloid PET in the diagnosis of chronic traumatic encephalopathies: studies of a retired NFL player and of a man with FTD and a severe head injury” Transl Psychiatry 2014; DOI: 10.1038/tp.2014.91.

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