Visual rating of dementia PET scans stumps some readers

Amyloid imaging can tell Alzheimer’s disease (AD) and frontotemporal dementia (FTD) apart because FTD typically does not show the same pattern of amyloid, right? Not so fast, say brain researchers.

Amyvid, a F-18 florbetapir injection, was first FDA approved in April, 2012, and made a big splash in amyloid imaging as a diagnostic aid for AD. It is well understood by now that the agent does not diagnose AD, but the absence of amyloid deposition is a green light for ruling out the disease. Alzheimer’s disease is not the only form of dementia being investigated with brain PET. It just so happens that FTD can also present patterns of amyloid deposition—although significantly less so. Researchers hoped that F-18 florbetapir would be helpful for discerning one dementia from the next, but it turns out that it is a little more complicated than that.

Christopher Kobylecki, PhD, a neurologist from the Institute of Brain, Behavior and Mental Health at the University of Manchester, U.K., and colleagues conducted the study, published Feb. 5 in the Journal of Nuclear Medicine.

“FTD is the second most common cause of presenile dementia, typically presenting with early loss of insight and behavioral change,” wrote Kobylecki. “However, early diagnosis may be challenging given the overlap between clinical features seen in FTD and other neurodegenerative conditions such as AD. Clinicopathological studies suggest that 10-20 percent of patients with a clinical diagnosis of FTD have AD pathology, while the standard clinical criteria for AD prior to 2011 had poor diagnostic specificity.”

For this first-of-its-kind blinded and prospective study, researchers assessed F-18 florbetapir PET scans of patients with either AD or FTD to determine if readers could accurately tell the two apart when they have no clue about prior clinical information or suspected diagnosis.

The investigators looked at F-18 florbetapir and FDG PET scans of eight patients with FTD, 10 patients with AD and 10 healthy controls with a mean age of about 63. Study participants also underwent MR imaging and genotyping for their apolipoprotein E (APOE) status, which indicates a higher risk of developing AD.

Study results showed that AD patients had markedly more cortical amyloid uptake than most FTD and control patients, including the posterior and anterior cingulate cortex, the frontal, parietal and occipital neocortex, and subcortical grey matter regions. However, visual rating of FTD patients was a challenge for blinded readers and revealed statistically significant discordance.

“The visual read data in our study with respect to AD patients and controls were comparable to those reported in previous studies and in line with the overlap seen on regional analysis between patients with AD and healthy controls,” wrote the authors. “However, rating FTD patients was challenging, with only two of eight FTD scans unanimously rated as negative and the high disagreement rate indicated considerable uncertainty, while quantitative regional analysis identified increased global cortical binding comparable to AD in only one FTD patient.”

A retrospective investigation using MR revealed how severe cortical atrophy represented a confounding factor that threw off readers due to its effect of mirroring high cortical uptake in certain regions, thus reducing the clear contrast between grey and white matter that readers use as a guidepost for interpretation. Some AD subjects did not show a model pattern of amyloid and, in other cases, small amounts of head movement affected interpretation.

The researchers said further research needs to be conducted in larger patient populations on standardized clinical scanners in order to get a better handle on the discordance of the visual read. A specialized research group well versed in the interpretation of such scans conducted this study. Discordance could be even greater in general clinical practice. It will be hard to tell without more numbers.

“Our observations underline that referring physicians should evaluate amyloid PET scan results in the context of clinical findings,” the researchers wrote. “Moreover, it may be useful for readers to indicate when the presentation is atypical and classification is uncertain. In our series, we would not have changed the clinical diagnosis in any of the FTD patients, but the scans made us aware of additional amyloid pathology in at least one of them.”