Twenty cognitively normal (CN), 17 amnestic mild cognitive impairment (aMCI), and 8 subjects with probable Alzheimer's disease (AD) were imaged with both magnetic resonance imaging (MRI) and the amyloid labeling ligand 11C Pittsburgh Compound B (PiB). PiB retention was quantified as the ratio of uptake in cortical regions of interest (ROIs) to the uptake in the cerebellar ROI in images acquired 40-60 minute post injection. A global cortical PiB retention summary measure was derived from six cortical ROIs. Statistical parametric mapping (SPM) and voxel-based morphometry (VBM) were used to evaluate PiB retention and grey matter loss on a 3D voxel-wise basis.
AD subjects had high global cortical PiB retention and low hippocampal volume; most CN subjects had low PiB retention and high hippocampal volume; and on average aMCI subjects were intermediate on both PiB and hippocampal volume. A target-to-cerebellar ratio of 1.5 was used to designate subjects as high vs. low PiB cortical retention. All AD subjects fell above this ratio as did 6/20 CN subjects and 9/17 MCI subjects, indicating bi-modal PiB retention in CN and aMCI. Interestingly, we found no consistent differences in learning and memory performance between high vs. low PiB CN subjects or high vs. low aMCI subjects.
The SPM/VBM voxel-wise comparisons of AD vs. CN subjects provided complementary information in that clear and meaningful similarities and differences in topographic distribution of amyloid deposition and grey matter loss were shown. The frontal lobes had high PiB retention with little grey matter loss. Anteromedial temporal areas had low PiB retention with significant grey matter loss. Lateral temporoparietal association cortex displayed both significant PiB retention and grey matter loss.
A voxel-wise SPM conjunction analysis of PiB uptake revealed that subjects with high PiB retention (high CN, high aMCI, and AD) shared a common PiB retention topographic pattern regardless of clinical category, and this PiB topographic pattern matched that of amyloid plaque distribution that has been established in autopsy studies of AD.
Both global cortical PiB retention and hippocampal volumes demonstrated significant correlation in the expected direction with cognitive testing performance; however, correlations were stronger with MRI than PiB. Pair-wise inter-group diagnostic separation was significant for all group-wise pairs for both PiB and hippocampal volume with the exception of CN vs. aMCI which was not significant for PiB. PiB and MRI provided complementary information such that clinical diagnostic classification with both, in combination, was superior to either alone.