. Relation between hypometabolism, impaired functional connectivity and ß-amyloid load in pre-dementia stages of Alzheimer’s disease. Human Amyloid Imaging 2010 Meeting Abstracts. 2010 April 9;


Objectives: In Alzheimer’s disease (AD) and mild cognitive impairment (MCI), specific patterns of cerebral hypometabolism and disrupted functional connectivity have been reported. New functional MRI-methods allow the identification of cortical hubs, i.e. regions with high functional, whole-brain connectivity (WBC), without restriction to specific networks. Aim of this study was to assess changes in cerebral metabolism and WBC in relation to β-amyloid load in pre-dementia-stages of AD.

Methods: Thirty-seven older subjects underwent resting state BOLD-fMRI to measure WBC, [18F]FDG PET for assessment of cerebral glucose metabolism and [11C]PIB PET for evaluation of amyloid-plaque load. PIBuptake ratios were calculated within a ROI including frontal, temporoparietal, and retrosplenial cortices (FLRROI), using the cerebellum as reference region. Based on a FLR-threshold of 1.15, subjects were divided into PIB-positive(+) and -negative(-). Three age-matched groups were studied: A) 12 PIB(-) controls, B) 12 PIB(+) controls, C) 13 PIB(+) MCI patients. Voxel-based and ROI-based statistical analyses were performed. The overlap between hypometabolism and WBC abnormalities in MCI was used to define a ROI to extract values for correlation analysis between different modalities.

Results: Group comparison between MCI and PIB(-) controls revealed significant hypometabolism and regionally overlapping WBC-reductions in MCI in posterior cingulate and parietal cortex (typical cortical hubs). PIB-FLR values were negatively correlated with FDG (r=-0.67) and WBC values (r=-0.42), and a linear positive correlation was found between FDG and WBC-values (r=0.51) across the entire population (groups A, B and C). These results survived correction for age and grey matter density.

Conclusions: In MCI, reduced WBC was found in cortical hub regions regionally overlapping with local hypometabolism, suggesting that these abnormalities may be interrelated. Across all subjects, both metabolic and functional changes demonstrated a significant relationship with amyloid-load, indicating that they reflect early neurodegenerative changes in AD, progressively evolving prior to symptomatic onset of dementia.


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