Dissociating atrophy and hypometabolism impact on episodic memory in mild cognitive impairment.
ABSTRACT The present study aims to unravel, in the same study, both morphological and functional specific substrates of encoding versus retrieval deficits in patients with amnestic mild cognitive impairment (MCI). For this purpose, 21 highly screened MCI patients with isolated memory impairment, who attended a memory clinic and fulfilled operational criteria for MCI, underwent (i) two episodic memory subtests designed to assess preferentially either incidental encoding or retrieval capacity; (ii) a high-resolution T1-weighted volume MRI scan; and (iii) a resting state [18F]fluoro-2-deoxy-D-glucose PET study. Using statistical parametric mapping, positive correlations between memory scores on one hand, and grey matter density and normalized partial volume effect-corrected brain glucose utilization (ncCMRglc) on the other hand, were computed. Deficits in both encoding and retrieval were correlated with declines in hippocampal region grey matter density. The encoding subtest also correlated with hippocampal ncCMRglc, whereas the retrieval subtest correlated with the posterior cingulate area ncCMRglc only. The present findings highlight a distinction in the neural substrates of encoding and retrieval deficits in MCI. Furthermore, they unravel a partial dissociation between metabolic and structural correlates, suggesting distinct interpretations. Hippocampal atrophy was related to both encoding and retrieval deficits, possibly reflecting a direct effect on hippocampal functioning, as well as an indirect effect, through remote functional disruption, on posterior cingulate region synaptic function, respectively.
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ABSTRACT: Background: Cognitive deficits may occur early in Parkinson’s disease (PD) but the extent of cortical involvement associated with cognitive dysfunction needs additional investigations. The aim of our study is to identify the anatomical pattern of cortical thickness alterations in patients with early stage PD and its relationship with cognitive disability. Methods: We recruited 29 PD patients and 21 healthy controls. All PD patients performed an extensive neuropsychological examination and 14 were diagnosed with mild cognitive impairment (PD-MCI). Surface-based cortical thickness analysis was applied to investigate the topographical distribution of cortical and subcortical alterations in early PD compared with controls and to assess the relationship between cognition and regional cortical changes in PD-MCI. Results: Overall PD patients showed focal cortical (occipital-parietal areas, orbito-frontal and olfactory areas) and subcortical thinning when compared with controls. PD-MCI showed a wide spectrum of cognitive deficits and related significant regional thickening in the right parietal-frontal as well as in the left temporal-occipital areas. Conclusion: Our results confirm the presence of changes in grey matter thickness at relatively early PD stage and support previous studies showing thinning and atrophy in the neocortex and subcortical regions. Relative cortical thickening in PD- MCI may instead express compensatory neuroplasticity. Brain reserve mechanisms might first modulate cognitive decline during the initial stages of PD.PLoS ONE 05/2013; · 3.53 Impact Factor
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ABSTRACT: Exploratory (i.e., voxelwise) spatial methods are commonly used in neuroimaging to identify areas that show an effect when a region-of-interest (ROI) analysis cannot be performed because no strong a priori anatomical hypothesis exists. However, noise at a single voxel is much higher than noise in a ROI making noise management critical to successful exploratory analysis. This work explores how preprocessing choices affect the bias and variability of voxelwise kinetic modeling analysis of brain positron emission tomography (PET) data. These choices include the use of volume- or cortical surface-based smoothing, level of smoothing, use of voxelwise partial volume correction (PVC), and PVC masking threshold. PVC was implemented using the Muller-Gartner method with the masking out of voxels with low gray matter (GM) partial volume fraction. Dynamic PET scans of an antagonist serotonin-4 receptor radioligand ([(11)C]SB2307145) were collected on sixteen healthy subjects using a Siemens HRRT PET scanner. Kinetic modeling was used to compute maps of non-displaceable binding potential (BPND) after preprocessing. The results showed a complicated interaction between smoothing, PVC, and masking on BPND estimates. Volume-based smoothing resulted in large bias and intersubject variance because it smears signal across tissue types. In some cases, PVC with volume smoothing paradoxically caused the estimated BPND to be less than when no PVC was used at all. When applied in the absence of PVC, cortical surface-based smoothing resulted in dramatically less bias and the least variance of the methods tested for smoothing levels 5mm and higher. When used in combination with PVC, surface-based smoothing minimized the bias without significantly increasing the variance. Surface-based smoothing resulted in 2-4 times less intersubject variance than when volume smoothing was used. This translates into more than 4 times fewer subjects needed in a group analysis to achieve similarly powered statistical tests. Surface-based smoothing has less bias and variance because it respects cortical geometry by smoothing the PET data only along the cortical ribbon and so does not contaminate the GM signal with that of white matter and cerebrospinal fluid. The use of surface-based analysis in PET should result in substantial improvements in the reliability and detectability of effects in exploratory PET analysis, with or without PVC.NeuroImage 12/2013; · 6.25 Impact Factor
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ABSTRACT: Alzheimer's disease (AD) and semantic dementia (SD) are both characterized by severe atrophy in the hippocampus, a brain region underlying episodic memory; paradoxically, episodic memory is relatively preserved in SD. Here, we used intrinsic connectivity analyses and showed that the brain networks differentially vulnerable to each disease converge to the hippocampus in the healthy brain. As neurodegeneration is thought to spread within preexisting networks, the common hippocampal atrophy in both diseases is likely due to its location at the crossroad between both vulnerable networks. Yet, we showed that in the normal brain, these networks harbor different functions, with episodic memory relying on the AD-vulnerable network only. Overall, disease-associated cognitive deficits seem to reflect the disruption of targeted networks more than atrophy in specific brain regions: in AD, over hippocampal atrophy, episodic memory deficits are likely due to disconnection within a memory-related network.Neuron 03/2014; 81(6):1417-28. · 15.77 Impact Factor