Theoretical Impact of Florbetapir (18F) Amyloid Imaging on Diagnosis of Alzheimer Dementia and Detection of Preclinical Cortical Amyloid

In 2012, florbetapir (F) (Amyvid) received US Food and Drug Administration approval as a diagnostic agent for detecting neuritic (β-amyloid) plaques in living patients. Although such approval is specifically not extended to the use of florbetapir as a single definitive diagnostic test for Alzheimer disease dementia (ADD), it is of considerable importance to examine its potential in this regard. To estimate the ability of florbetapir amyloid imaging to detect specified densities of postmortem-identified neuritic plaques, we used the data of Clark et al [Clark CM, Pontecorvo MJ, Beach TG, et al. Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-beta plaques: A prospective cohort study. Lancet Neurol 2012;11:669-78]. We then used the data of Beach et al [Beach TG, Monsell SE, Phillips LE, et al. Accuracy of the clinical diagnosis of Alzheimer disease at National Institute on Aging Alzheimer Disease Centers, 2005-2010. J Neuropathol Exp Neurol 2012;71:266-73], derived from the National Alzheimer's Coordinating Center, to estimate the fraction of subjects who would have been called florbetapir-positive and, among these, the fraction of subjects who would also meet neuropathologic criteria for the presence of ADD. The accuracy of a positive florbetapir β-amyloid scan for the detection of neuropathologically defined ADD is estimated at between 69% and 95% sensitivity and between 83% and 89% specificity. From the same National Alzheimer's Coordinating Center data set, 144 subjects were recorded as having normal cognition. Among these, 84 (58%) had at least sparse neuritic plaques at autopsy and, among these, florbetapir imaging was estimated to detect 47 (56%). These findings suggest that amyloid imaging may significantly improve the clinical identification of ADD