Structural and molecular changes along the continuum of Alzheimer's disease

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Background: Several methods are available for in vivo detection of structural and molecular changes in Alzheimer's disease (AD): [(11)C]PIB PET measures the distribution of fibrillary Ass, voxel-based morphometry (VBM) can be used to assess grey matter (GM) density, and [(18)F]FDG PET reflects metabolic activity. The unique study design allowed us to compare these methods in the same patients with AD, MCI and controls. Methods: Forty-five subjects were included (AD = 15; MCI = 15; controls = 15). In all subjects structural MRI (including T1-weighted 3D MPRAGE) scans, and dynamic [(11)C]PIB (90 minutes) and static [(18)F]FDG PET scans were acquired. We created a study specific GM template by averaging the GM segmentations of all subjects using SPM8's DARTEL tool. Next, parametric PET images (BPND for [(11)C]PIB, SUVr45-60 for [(18)F]FDG) were nonlinearly registered to the GM template in standard (MNI) space.We applied a full factorial design and used voxelwise t-contrasts to evaluate differences amongst the three groups. Level of significance was set to p <0.001 for the comparison between AD and controls. P-values below 0.01 were considered to be significant for the contrasts comparing MCI patients and controls. Results: In the AD group, an increase in [(11)C]-PIB binding was observed throughout the necortex. VBM revealed lower GM density in the posterior (Figure presented) cingulate and right medial temporal lobe. Reduced [(18)F]FDG uptake was found in the posterior cingulate and bilateral parietal cortex and bilateral hippocampus. MCI patients showed significantly more [(11)C]PIB binding compared to controls, predominantly in the posterior cingulate and occipital and frontal cortices. VBM showed lower GM density in the bilateral hippocampus and the right inferior frontal cortex. No differences in cerebral glucose metabolism were found. Analysis of reversed contrasts did not lead to any unexpected findings in the control group. Conclusions: Amyloid deposits, brain atrophy and reduced glucose metabolism were all present in AD patients. The MCI group showed elevated levels of [(11)C]PIB binding in highly susceptible brain areas such as the posterior cingulate and the frontal cortex. However, only subtle morphological changes and no metabolic impairment were found. These findings are in accordance with the hypothesis that accumulation of Ass precedes structural and functional changes in AD
Original languageEnglish
Publication statusPublished - 2 Aug 2011

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