Drzezga A, Becker JA, Sreenivasan A, Talukdar T, Van Dijk K, Sullivan C, Schultz AP, Sepulcre J, Buckner RL, Sperling RA.
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.