Experimental sepsis-associated encephalopathy is accompanied by altered cerebral blood perfusion and water diffusion and related to changes in cyclooxygenase-2 expression and glial cell morphology but not to blood-brain barrier breakdown.

Sepsis-associated encephalopathy (SAE) refers to brain dysfunction, including delirium, occurs during severe infection and is associated with development of post-traumatic stress disorder. SAE has been proposed to be related to reduced cerebral blood flow (CBF), blood-brain barrier breakdown (BBB), white matter edema and disruption and glia cell activation, but their exact relationships remain to be determined. In the present work, we set out to study CBF using Arterial Spin Labeling (ASL) and grey and white matter structure with T2- and diffusion magnetic resonance imaging (dMRI) in rats with cecal ligation and puncture (CLP)-induced encephalopathy. Using immunohistochemistry, the distribution of the vasoactive prostaglandin-synthesizing enzyme cyclooxygenase-2 (COX-2), perivascular immunoglobulins G (IgG), aquaporin-4 (AQP4) and the morphology of glial cell were subsequently assessed in brains of the same animals. CLP induced deficits in the righting reflex and resulted in higher T2-weighted contrast intensities in the cortex, striatum and at the base of the brain, decreased blood perfusion distribution to the cortex and increased water diffusion parallel to the fibers of the corpus callosum compared to sham surgery. In addition, CLP reduced staining for microglia- and astrocytic-specific proteins in the corpus callosum, decreased neuronal COX-2 and AQP4 expression in the cortex while inducing perivascular COX-2 expression, but did not induce widespread perivascular IgG diffusion. In conclusion, our findings indicate that experimental SAE can occur in the absence of BBB breakdown and is accompanied by increased water diffusion anisotropy and altered glia cell morphology in brain white matter.

Mediterranean diet and preserved brain structural connectivity in older subjects.

INTRODUCTION: The Mediterranean diet (MeDi) has been related to a lower risk of Alzheimer's disease; yet, the underlying mechanisms are unknown. We hypothesized that protection against neurodegeneration would translate into higher gray matter volumes, whereas a specific association with preserved white matter microstructure would suggest alternative mechanisms (e.g., vascular pathways). METHODS: We included 146 participants from the Bordeaux Three-City study nondemented when they completed a dietary questionnaire and who underwent a 3-T magnetic resonance imaging at an average of 9 years later, including diffusion tensor imaging. RESULTS: In multivariate voxel-by-voxel analyses, adherence to the MeDi was significantly associated with preserved white matter microstructure in extensive areas, a gain in structural connectivity that was related to strong cognitive benefits. In contrast, we found no relation with gray matter volumes. DISCUSSION: The MeDi appears to benefit brain health through preservation of structural connectivity. Potential mediation by a favorable impact on brain vasculature deserves further research.

Changes Over Time of Diffusion MRI in the White Matter of Aging Brain, a Good Predictor of Verbal Recall.

Objective: Extensive research using water-diffusion MRI reported age-related modifications of cerebral White Matter (WM). Moreover, water-diffusion parameter modifications have been frequently associated with cognitive performances in the elderly sample, reinforcing the idea of aging inducing microstructural disconnection of the brain which in turn impacts cognition. However, only few studies really assessed over-time modifications of these parameters and their relationship with episodic memory outcome of elderly. Materials and Methods: One-hundred and thirty elderly subjects without dementia (74.1 ± 4.1 years; 47% female) were included in this study. Diffusion tensor imaging (DTI) was performed at two-time points (3.49 ± 0.68 years apart), allowing the assessment of changes in water-diffusion parameters over time using a specific longitudinal pipeline. White matter hyperintensity (WMH) burden and gray matter (GM) atrophy were also measured on FLAIR and T1-weighted sequences collected during these two MRI sessions. Free and cued verbal recall scores assessed at the last follow-up of the cohort were used as episodic memory outcome. Changes in water-diffusion parameters over time were included in serial linear regression models to predict retrieval or storage ability of elderly. Results: GM atrophy and an increase in mean diffusivity (MD) and WMH load between the two-time points were observed. The increase in MD was significantly correlated with WMH load and the different memory scores. In models accounting for the baseline cognitive score, GM atrophy, or WMH load, MD changes still significantly predict free verbal recall, and not total verbal recall, suggesting the specific association with the retrieval deficit in healthy aging. Conclusion: In elderly, microstructural WM changes are good predictors of lower free verbal recall performances. Moreover, this contribution is not only driven by WMH load increase. This last observation is in line with studies reporting early water-diffusion modification in WM tissue during aging, resulting lately in the appearance of WMH on conventional MRI.

Vascular Cerebral Damage in Frail Older Adults: The AMImage Study.

BACKGROUND: Frailty has been associated with increased risk of adverse-health related outcomes including cognitive impairment. However, little is know about the pathogenesis relating frailty to cognitive decline. Therefore, the main objective of this study was to investigate the association between vascular cerebral damage and frailty. METHODS: Cross-sectional study involving 176 community-dwelling participants aged 67-86 years, participating in the AMImage Study, an ancillary neuro-imaging project of the AMI cohort, a French prospective cohort including older farmers living in rural areas. Frailty was defined as proposed by Fried. 3T magnetic resonance imaging (MRI) examination was performed with anatomical, diffusion, and fluid-attenuated inversion recovery sequences. The evaluation included the assessment of white matter hyperintensities (WMH) volumes and of microstructural white matter integrity through exploration of diffusion tensor imaging (DTI) parameters. RESULTS: The analyses showed that WMH volumes were higher in frail persons compared with nonfrail subgroup. Frail participants presented DTI modifications in extensive areas of white matter. In comparison with nonfrail subgroup, frail participants showed a strong association between WMH volumes and DTI changes. CONCLUSION: These results show that subclinical cerebrovascular damage is present in the frail older person, which could support the hypothesis that frailty is a prodromal state of central nervous system vascular injury.

Age-Related Modifications of Diffusion Tensor Imaging Parameters and White Matter Hyperintensities as Inter-Dependent Processes.

Microstructural changes of White Matter (WM) associated with aging have been widely described through Diffusion Tensor Imaging (DTI) parameters. In parallel, White Matter Hyperintensities (WMH) as observed on a T2-weighted MRI are extremely common in older individuals. However, few studies have investigated both phenomena conjointly. The present study investigates aging effects on DTI parameters in absence and in presence of WMH. Diffusion maps were constructed based on 21 directions DTI scans of young adults (n = 19, mean age = 33 SD = 7.4) and two age-matched groups of older adults, one presenting low-level-WMH (n = 20, mean age = 78, SD = 3.2) and one presenting high-level-WMH (n = 20, mean age = 79, SD = 5.4). Older subjects with low-level-WMH presented modifications of DTI parameters in comparison to younger subjects, fitting with the DTI pattern classically described in aging, i.e., Fractional Anisotropy (FA) decrease/Radial Diffusivity (RD) increase. Furthermore, older subjects with high-level-WMH showed higher DTI modifications in Normal Appearing White Matter (NAWM) in comparison to those with low-level-WMH. Finally, in older subjects with high-level-WMH, FA, and RD values of NAWM were associated with to WMH burden. Therefore, our findings suggest that DTI modifications and the presence of WMH would be two inter-dependent processes but occurring within different temporal windows. DTI changes would reflect the early phase of white matter changes and WMH would appear as a consequence of those changes.

Structural hippocampal network alterations during healthy aging: a multi-modal MRI study.

While hippocampal atrophy has been described during healthy aging, few studies have examined its relationship with the integrity of White Matter (WM) connecting tracts of the limbic system. This investigation examined WM structural damage specifically related to hippocampal atrophy in healthy aging subjects (n = 129), using morphological MRI to assess hippocampal volume and Diffusion Tensor Imaging (DTI) to assess WM integrity. Subjects with Mild Cognitive Impairment (MCI) or dementia were excluded from the analysis. In our sample, increasing age was significantly associated with reduced hippocampal volume and reduced Fractional Anisotropy (FA) at the level of the fornix and the cingulum bundle. The findings also demonstrate that hippocampal atrophy was specifically associated with reduced FA of the fornix bundle, but it was not related to alteration of the cingulum bundle. Our results indicate that the relationship between hippocampal atrophy and fornix FA values is not due to an independent effect of age on both structures. A recursive regression procedure was applied to evaluate sequential relationships between the alterations of these two brain structures. When both hippocampal atrophy and fornix FA values were included in the same model to predict age, fornix FA values remained significant whereas hippocampal atrophy was no longer significantly associated with age. According to this latter finding, hippocampal atrophy in healthy aging could be mediated by a loss of fornix connections. Structural alterations of this part of the limbic system, which have been associated with neurodegeneration in Alzheimer's disease, result at least in part from the aging process.

Distinctive alterations of the cingulum bundle during aging and Alzheimer's disease.

Brain imaging studies have revealed frontal disruption during aging and parieto-temporal disruption during Alzheimer's disease (AD). The present study aims at developing a specific method based on precise anatomical landmarks for assessing the integrity all along the course of the cingulum bundle, so as to determine if it presents the classical aging and AD dissociation. Five regions of interest (ROIs) were placed on fractional anisotropy (FA) maps all along the cingulum in 15 young (Gyoung), 15 70-year-old (Gold), and 15 AD subjects (Galz). An age-related decrease of FA occurred in the anterior part of the bundle. Moreover, a specific alteration of the supero-posterior region of the cingulum during AD was observed since mean FA values as well as mean number of fibers were significantly decreased in Galz compared to Gold and Gyoung. This multiple ROIs placement allows for revealing distinctive alterations of the cingulum bundle during aging and AD, which could constitute the anatomical basis for the distinctive functional disconnection recently described in the literature using functional connectivity at rest.