Journal
NEUROIMAGE
Volume 176, Issue -, Pages 246-258Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.neuroimage.2018.04.048
Keywords
Mild cognitive impairment; Alzheimer disease; Fludeoxyglucose PET; Brain functional MRI; Intrinsic functional connectivity; Default mode network
Funding
- Italian Ministry of Health
- European Union's Seventh Framework Programme (FP7) [HEALTH-F2-2011-278850-INMiND]
- CNR Strategic Project The Aging: Technological and Molecular Innovations Aiming to Improve the Health of Older Citizens
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Simultaneously evaluating resting-state brain glucose metabolism and intrinsic functional activity has potential to impact the clinical neurosciences of Alzheimer Disease (AD). Indeed, integrating such combined information obtained in the same physiological setting may clarify how impairments in neuroenergetic and neuronal function interact and contribute to the mechanisms underlying AD. The present study used this multimodality approach to investigate, by means of a hybrid PET/MR scanner, the coupling between glucose consumption and intrinsic functional activity in 23 patients with AD-related cognitive impairment ranging from amnestic mild cognitive impairment (MCI) to mild-moderate AD (aMCI/AD), in comparison with a group of 23 healthy elderly controls. Between-group (Controls > Patients) comparisons were conducted on data from both imaging modalities using voxelwise 2-sample t-tests, corrected for partial-volume effects, head motion, age, gender and multiple tests. FDGPET/fMRI relationships were assessed within and across subjects using Spearman partial correlations for three different resting-state fMRI (rs-fMRI) metrics sensitive to AD: fractional amplitude of low frequency fluctuations (fALFF), regional homogeneity (ReHo) and group independent component analysis with dual regression (gICADR). FDG and rs-fMRI metrics distinguished aMCI/AD from controls according to spatial patterns analogous to those found in stand-alone studies. Within-subject correlations were comparable across the three rs-fMRI metrics. Correlations were overall high in healthy controls (rho=0.80 +/- 0.04), but showed a significant 17% reduction (p < 0.05) in aMCI/AD patients (rho= 0.67 +/- 0.05). Positive across-subject correlations were overall moderate (rho=0.33 +/- 0.07) and consistent across rs-fMRI metrics. These were confined around AD-target posterior regions for metrics of functional connectivity (ReHo and gICA-DR). In contrast, FDG/fALFF correlations were distributed in the frontal gyrus, thalami and caudate nuclei. Taken together, these results support the presence of bioenergetic coupling between glucose utilization and rapid transmission of neural information in healthy ageing, which is substantially reduced in aMCI/AD, suggesting that abnormal glucose utilization is in some way linked to communication breakdown among brain regions impacted by the underlying pathological process.
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