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We continue to lack a diagnostic test for Alzheimer disease (AD). Pittsburgh Compound B (PIB), a radiotracer that binds fibrillar amyloid, may provide such a tool. These authors compared PIB-PET scans to fluorodeoxyglucose (FDG)-PET scans of regional cerebral glucose metabolism and to cognitive-function findings. Nineteen subjects with clinical AD and 14 age-matched normal subjects underwent PIB-PET and neuropsychological testing. A subset of each group underwent FDG-PET.
AD subjects showed twofold increases in PIB binding compared with normal subjects in multiple brain regions including frontal, temporal, and parietal cortex. Most (17 of 19) AD subjects and few (2 of 14) control subjects had high PIB binding. Higher amyloid burden correlated with lower scores for recognition memory, but this effect disappeared when amyloid-negative AD subjects were excluded from analysis. Regional glucose metabolism was reduced in most (10 of 12) AD subjects and correlated with cognitive test performance. In temporal and parietal regions, but not in frontal regions, higher PIB uptake correlated with lower glucose metabolism.
Edison P et al. Amyloid, hypometabolism, and cognition in Alzheimer disease: An [11C]PIB and [18F]FDG PET study. Neurology 2007 Feb 13; 68:501-8.
Comment
The key finding of this study — that PIB-PET discriminates AD subjects from normal subjects — is consistent with a growing number of studies. Imaging AD pathology with the PET agent FDDNP has shown similar qualitative findings. Although PIB-PET and FDG-PET had comparable sensitivities, PIB-PET better separated AD from normal subjects. The dissociation between amyloid and glucose metabolism in frontal regions suggests that amyloid deposition is not sufficient for the regional hypometabolism seen in AD. Larger controlled studies, evaluation of PIB-PET in other dementias, and further correlations of PIB-PET with neuropathologic findings (such as cerebral amyloid angiopathy) will be necessary to define the sensitivity and specificity of amyloid imaging as a diagnostic test for AD and as a biomarker for emerging therapeutic strategies.