Clinical different stage of Alzheimer's disease associated with amyloid load by [11C] PiB-PET imaging

Abstract

The AD pathology is detectable in vivo using selective imaging ligand for beta-amyloid by carbon 11-labeled Pittsburgh Compound B ([11C]-PIB) PET. We clarify the association between cerebral amyloid load, glucose metabolism and cognitive function in clinical different stage of Alzheimer's disease (AD) and mild cognitive impairment (MCI). 128 patients who met criteria for AD or MCI and 81 age-matched healthy controls (HC) were included. Subjects underwent cognitive testing, 60-min dynamic [11C]-PIB PET and 15-min static [18F]-FDG PET imaging. Regions of interest (ROI) were defined on co-registered MRI. Distribution volume ratios (DVR) of PIB retention were determined by Logan graphical analysis (cerebellar gray as reference region). [18F]-FDG PET images were extracted using 3 dimensional stereotactic surface projections (3D-SSP). Quantitative analysis for [18F]-FDG used the standardized uptake value ratio (SUVR) values of same cortical areas. The patients with cortical PIB retention were classified into AD dementia, prodromal and preclinical AD groups as clinical different stage of AD. All of 95 patients with AD dementia, prodromal and preclinical AD had a robust increase of PIB binding in cortical areas (typical PIB AD-pattern). The mean DVR value of whole cortical areas in these groups increased significantly compared with PIB negative MCI or HC. The DVR value in 49 AD dementia (MMSE: 19.0 ± 5.1, CDR: 0.92 ± 0.57) was the highest among all groups (2.31 ± 0.46, P < 0.01). The DVR value in 36 prodromal AD (MMSE: 27.4 ± 1.9, CDR: 0.5) and 10 preclinical AD (MMSE: 28.9 ± 1.1, CDR: 0) were 2.05 ± 0.30 and 1.88 ± 0.27, respectively. The cortical PIB retention was significantly correlated to MMSE scores in these groups (r=-0.27, n = 94, P < 0.01). On FDG PET 3D-SSP images, in contrast, twenty-four (51%) of AD dementia showed a significant reduction of glucose metabolism in temporo-parietal cortex (metabolic AD-pattern). In prodromal AD only two patients (6%) had classic metabolic AD-pattern. There was no hypometabolism in any of cortical areas in preclinical AD. The increased PIB bindings did not correlate to comparable metabolic decreases in cortical areas of these groups. This diagnostic framework with brain amyloid deposition, in clinical different stage of AD, would allow an earlier and more specific AD diagnosis and play an important role of anti-amyloid strategies.