PET Amyloid imaging and cognition in patients with Alzheimer's disease, Mild Cognitive Impairment (MCI) and healthy controls: a European multicenter study

Background: PIB is so far the most explored amyloid PET ligand. We have compiled PET and cognitive data from six different European research centres in order to be able discriminate PIB binding in AD versus MCI and controls in a large set of subjects and also to relate to cognitive performances. Methods: 102 AD patients (51 male, 51 females, 69 ± 8 yrs, MMSE 23.9 ± 3), 73 MCI patients (38 males, 35 females, 67 ± 8 yrs, MMSE 27.1 ± 2.0) and 52 healthy controls (22 males, 30 females, 67 ± 6, MMSE 29.1 ± 1.1) underwent 40-60 min PIB imaging. Individual PIB images from each centre were non-linearly spatially normalized to a PIB template using SPM5. The PIB binding was expressed relative to the mean PIB binding in the cerebellar grey matter. All subjects underwent neuropsychology tests for general cognitive state, verbal memory, attention, visuo-construction and non-verbal memory. Results: No significant difference was observed between age, sex or education between AD, MCI and controls. A significant (p< 0.0001) higher cortical PIB binding (composite fronto-temporal-parietal regions) was observed in AD patients (1.84 ± 0.32, N = 98) compared to controls (1.30 ± 0.15, N = 51). The cortical PIB binding in MCI patients was intermediate (1.64 ± 0.35, N = 72) and significantly different from both AD and controls. The PIB binding in the control group was bimodal with 5 subjects showing abnormally high uptake. A significant correlation was observed between neuropsychological tests such as verbal and visual delayed recall and cortical PIB binding in the MCI patients. A highly significant effect of ApoE genotype was observed on PIB binding in the MCI group. Out of 48 MCI patients who so far have been longitudinally followed up for 1 year, 15 have converted to AD. All MCI patients that converted to AD showed significantly higher cortical PIB uptake compared to controls. Conclusions: PIB PET imaging data was confirmed to be consistent from six different European centres. Significant differences in PIB binding were observed between MCI, AD and controls. Correlations between PIB binding and cognition were observed both in MCI and AD groups.

Cooperation supported by EC FP6 grant on Diagnostic Molecular Imaging (DiMI).