Charlotte Bernard

Cognitive disorders in HIV-infected patients: are they HIV-related?

Objectives:Large unselected studies on representative samples of HIV-infected patients with a whole battery of neuropsychological tests and cerebral MRI scan are required to assess the frequency of neurocognitive impairment (NCI), the determinants of mild neurocognitive disorders (MNDs), or HIV-associated dementia (HAD) and the relationship between NCI and MRI scan findings. Methods:Investigation of 400 consecutively enrolled HIV-1-infected adults from the ANRS CO3 Aquitaine Cohort, using standardized neurocognitive tests chosen to achieve consistency with Frascatis criteria. Half of the patients had a cerebral MRI scan allowing gray and white matter volume measurement. Factors associated with NCI were studied by logistic regression models. Results:Median age of participants was 47 years, 79% were male and 89% received combination antiretroviral treatment (cART), of whom 93% had plasma HIV RNA below 500 copies/ml. Median CD4 cell count was 515 cells/&mgr;l. Prevalence of NCI was 59%, including 21% of asymptomatic NCI, 31% of MND, and 7% of HAD. A low level of education, prior neurologic AIDS-defining disorders event, anxiety, depressive symptoms, and prior history of brain damage were independently associated with MND or HAD, but neither HIV nor cART-related variables. The presence of NCI was significantly associated with lower gray matter fraction. Interpretation:In this large unselected cohort, a high prevalence of symptomatic neurocognitive disorders was mainly related to its traditional determinants and associated with gray matter atrophy at early stages of the disease.

Time course of brain volume changes in the preclinical phase of Alzheimer's disease

Structural alterations of a large network characterize Alzheimers disease (AD), but the time course of these changes remains unclear. The dynamic of these alterations was examined in the AD preclinical phase using data from the 10‐year follow‐up of a population‐based cohort (Bordeaux‐3City).

Mediterranean diet and preserved brain structural connectivity in older subjects.

The Mediterranean diet (MeDi) has been related to a lower risk of Alzheimers 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).

Detection of Alzheimer's disease signature in MR images seven years before conversion to dementia: Toward an early individual prognosis.

Finding very early biomarkers of Alzheimers Disease (AD) to aid in individual prognosis is of major interest to accelerate the development of new therapies. Among the potential biomarkers, neurodegeneration measurements from MRI are considered as good candidates but have so far not been effective at the early stages of the pathology. Our objective is to investigate the efficiency of a new MR‐based hippocampal grading score to detect incident dementia in cognitively intact patients. This new score is based on a pattern recognition strategy, providing a grading measure that reflects the similarity of the anatomical patterns of the subject under study with dataset composed of healthy subjects and patients with AD. Hippocampal grading was evaluated on subjects from the Three‐City cohort, with a followup period of 12 years. Experiments demonstrate that hippocampal grading yields prediction accuracy up to 72.5% (P < 0.0001) 7 years before conversion to AD, better than both hippocampal volume (58.1%, P = 0.04) and MMSE score (56.9%, P = 0.08). The area under the ROC curve (AUC) supports the efficiency of imaging biomarkers with a gain of 8.4 percentage points for hippocampal grade (73.0%) over hippocampal volume (64.6%). Adaptation of the proposed framework to clinical score estimation is also presented. Compared with previous studies investigating new biomarkers for AD prediction over much shorter periods, the very long followup of the Three‐City cohort demonstrates the important clinical potential of the proposed imaging biomarker. The high accuracy obtained with this new imaging biomarker paves the way for computer‐based prognostic aides to help the clinician identify cognitively intact subjects that are at high risk to develop AD. Hum Brain Mapp 36:4758–4770, 2015.

Proposition of Atomic Force Probes Based on Silicon Ring-Resonators

We present the first implementation of an atomic force microscope (AFM) probe using bulk- mode silicon resonators. This probe is developed in order to perform force or dissipation spectroscopy and to enable AFM imaging in liquids thanks to reduced dissipation effects. We show that balanced tip integration allows the probe to operate in a lateral mode derived from elliptical bulk modes of circular plates. A proof-of-concept technological realization opens up the way to first AFM experiments using this resonator around 7 MHz frequencies.

Prevalence and factors associated with depression in people living with HIV in sub-Saharan Africa: A systematic review and meta-analysis

Depression, one of the most common psychiatric disorders, is two- to three-times more prevalent in people living with HIV (PLHIV) than in the general population in many settings as shown in western countries but remains neglected in sub-Saharan Africa (SSA). We aimed to summarize the available evidence on the prevalence of depression and associated factors according to the scales used and the treatment status in PLHIV in SSA. The pooled prevalence estimates of depression ranged between 9% and 32% in PLHIV on antiretroviral treatment (ART) and in untreated or mixed (treated/untreated) ones, with a substantial variability according to the measurement scale used and also for a given scale. Low socio-economic conditions in PLHIV on ART, female sex and immunosuppression in mixed/untreated PLHIV were frequently reported as associated factors but with no consensus. As depression could have deleterious consequences on the PLHIV life, it is critical to encourage its screening and management, integrating these dimensions in HIV care throughout SSA.

Competition of elastic and adhesive properties of carbon nanotubes anchored to atomic force microscopy tips

In this paper we address the mechanical properties of carbon nanotubes anchored to atomic force microscopy (AFM) tips in a detailed analysis of experimental results and exhaustive description of a simple model. We show that volume elastic and surface adhesive forces both contribute to the dynamical AFM experimental signals. Their respective weights depend on the nanotube properties and on an experimental parameter: the oscillation amplitude. To quantify the elastic and adhesive contributions, a simple analytical model is used. It enables analytical expressions of the resonance frequency shift and dissipation that can be measured in the atomic force microscopy dynamical frequency modulation mode. It includes the nanotube adhesive contribution to the frequency shift. Experimental data for single-wall and multi-wall carbon nanotubes compare well to the model predictions for different oscillation amplitudes. Three parameters can be extracted: the distance necessary to unstick the nanotube from the surface and two spring constants corresponding to tube compression and to the elastic force required to overcome the adhesion force.

Semantic retrieval over time in the aging brain: Structural evidence of hippocampal contribution

This study investigates relationship between regional cerebral volumes and performances over time of a categorical fluency task, in a sample of older adults (n = 316). Using voxel‐wise technique, the relationship between local grey matter volume and Isaacs Set Test (IST) scores at its early (first 15 sec) and late (last 15 sec) phase production was analyzed with a linear regression model adjusting for age, sex, educational level, ApoEɛ4 allele, handedness and Grey Matter atrophy. Lower early IST scores were associated with smaller volumes in bilateral inferior frontal gyri and in right thalamus, whereas lower late IST scores were associated to smaller left inferior parietal gyrus and left anterior hippocampus. An analysis based on automatic segmentation of hippocampus confirmed the latest relationship which cannot be attributed to the correlation of each variable with global cognitive impairment because it remained when MMSE was accounted for. We observed a switch from frontal to temporo‐parietal regions as words retrieval become more difficult over time. Automatic speech production of the early phase of the category fluency task is dependent on executive networks integrity whereas controlled speech production of the late phase is dependent on memory networks integrity, including left hippocampus. These results are concordant with recent imaging studies expanding the implication of hippocampus to semantic memory performances and they underlie the need to consider verbal fluency task over time.

Muscular Weakness in Individuals with HIV Associated with a Disorganization of the Cortico-Spinal Tract: A Multi-Modal MRI Investigation

Motor impairment is highly prevalent in HIV-infected patients. Here, we assess associations between peripheral muscular deficits as evaluated by the 5 sit-to-stand test (5STS) and structural integrity of the motor system at a central level. Eighty-six HIV-infected patients receiving combination antiretroviral therapy and with no major cerebral events, underwent an MRI scan and the 5STS. Out of 86 participants, forty presented a score greater than two standard deviations above mean normative scores calculated for the 5STS and were therefore considered as motor-impaired. MRI-structural cerebral parameters were compared to the unimpaired participants. Fractional Anisotropy (FA), Axial Diffusivity (AD) and Radial Diffusivity (RD), reflecting microstructural integrity, were extracted from Diffusion-Tensor MRI. Global and regional cerebral volumes or thicknesses were extracted from 3D-T1 morphological MRI. Whereas the two groups did not differ for any HIV variables, voxel-wise analysis revealed that motor-impaired participants present low FA values in various cortico-motor tracts and low AD in left cortico-spinal tract. However, they did not present reduced volumes or thicknesses of the precentral cortices compared to unimpaired participants. The absence of alterations in cortical regions holding motor-neurons might argue against neurodegenerative process as an explanation of White Matter (WM) disorganization.

PCC characteristics at rest in 10-year memory decliners.

The present research sought to characterize the intrinsic functional networks associated with a 10-year episodic memory decline in elderly using data from a longitudinal population-based cohort (Bordeaux-3City). Complementary measures of whole-brain resting-state functional magnetic resonance imaging investigations were combined to compare functional architecture of brain networks both at connectional and topological levels in 22 decliners to 22 nondecliners; episodic memory decline being assessed through a multiple time point Free and Cued Selective Reminding Test. The decliners presented differences in functional architecture centered on the posterior cingulate cortex, characterized by a significant decrease of connectivity intensity, a significant increased centrality. In accordance, a decrease of the functional connectivity inside the default mode network was observed in the decliners. Our results highlight the central role of the posterior cingulate cortex in a slow but reliable memory decline in elderly. Because functional alterations of this region are currently described in Alzheimers disease, this functional signature could constitute a risk for Alzheimers disease.