New Study Shows Beta-Amyloid Imaging Is Associated With Altered Diagnosis And Management Of Alzheimer's Disease

Eli Lilly and Company

today announced new data showing that beta-amyloid imaging was associated with altered diagnosis and management of patients with Alzheimer's disease. Change in management was observed in both patients who met and did not meet the Appropriate Use Criteria (AUC), which were developed by the Society of Nuclear Medicine and Molecular Imaging and the Alzheimer's Association to provide guidance on which patients are most appropriate for imaging and how best to use the results. These data were presented today at the Alzheimer's Association International Conference 2014 (AAIC 2014) in Copenhagen, Denmark by Andrew Siderowf, M.D., MSCE, medical director, Avid Radiopharmaceuticals, a wholly owned subsidiary of Lilly. The data were also featured by the AAIC in a research media tips sheet. "This study included patients in which there was diagnostic uncertainty by the treating physician and found that changes in diagnosis and management of Alzheimer's disease did not vary between patients depending on whether they met the Appropriate Use Criteria or not. In addition, analysis of beta-amyloid scans conducted post-diagnosis indicated that many patients being treated with medications may have potentially been misdiagnosed and inappropriately treated," said Dr. Siderowf. "While we support the development of the Appropriate Use Criteria, one of the clearest insights resulting from these data is that we need to continue to fine tune our understanding of the appropriate use of these tools and their utility for patients facing a diagnosis of Alzheimer's disease." The objective of the study was to evaluate which patients are most likely to receive different care if they had an amyloid PET scan as part of their diagnostic work-up. In particular, the study evaluated if patients who met the working definition of the AUC would be more affected than those who did not. The AUC guidelines propose that patients who are being evaluated for dementia with atypical presentations, younger patients, and patients with unexplained mild cognitive impairment, are most appropriate for amyloid PET imaging. For the patient to be included in the study, Alzheimer's disease had to be under consideration and the treating physician had to have uncertainty regarding the diagnosis. Results showed that 59 percent of subjects met the working definition of AUC. Forty-seven percent of the AUC-like cases were amyloid positive compared to 62 percent of non-AUC cases. Diagnosis changed after PET scan for 58 percent of AUC cases versus 45 percent of non-AUC cases (p=0.10). The proportion of patients with change in management plan was high for both AUC (88 percent) and non-AUC (77 percent) cases. In particular, the use of Alzheimer's disease medications including cholinesterase inhibitors, or memantine, declined after a negative florbetapir F 18 scan by 20 percent (from 26/54 to 15/54 cases; p=0.002) in AUC cases and by 33 percent (from 17/27 to 8/27 cases; p=0.004) in non-AUC cases. Diagnoses for non-AUC cases in which Alzheimer's disease medications were withdrawn after a negative scan included prodromal Alzheimer's disease/mild cognitive impairment due to Alzheimer's disease (n=8), or mild cognitive impairment of uncertain etiology (n=1). This study found that patients with an uncertain diagnosis, but who are not otherwise explicitly captured by AUC, may be reasonable candidates for amyloid imaging. "Alzheimer's disease is one of many possible causes of cognitive impairment, which can make diagnosis challenging. In fact, it is estimated that up to one in five patients clinically diagnosed with probable Alzheimer's disease during life do not exhibit Alzheimer's disease pathology upon autopsy[1],[2]," said Dr. Siderowf. "These results reinforce how knowledge of the presence or absence of amyloid pathology can substantially affect both diagnosis and management in these patients being evaluated for Alzheimer's disease or other possible causes of cognitive decline." Study Methods The impact of amyloid PET on actual patient care was examined in a previous study.[3] In the prior study, performed at 19 clinical sites, treating physicians provided a provisional diagnosis and management plan prior to receiving results of amyloid PET imaging with florbetapir F 18. Participants' medical records for the three months immediately after imaging were abstracted to capture their actual diagnosis and management. For the current study, participants were classified as meeting an operational definition of AUC-like or not, based on pre-scan diagnosis and demographic features.