Recognition-based memory through familiarity assessment in severe Alzheimer’s disease

peer reviewe

Exposure to negative socio-emotional events induces sustained alteration of resting-state brain networks in older adults

Basic emotional functions seem well preserved in older adults. However, their reactivity to and recovery from socially negative events remain poorly characterized. To address this, we designed a ‘task–rest’ paradigm in which 182 participants from two independent experiments underwent functional magnetic resonance imaging while exposed to socio-emotional videos. Experiment 1 (N = 55) validated the task in young and older participants and unveiled age-dependent effects on brain activity and connectivity that predominated in resting periods after (rather than during) negative social scenes. Crucially, emotional elicitation potentiated subsequent resting-state connectivity between default mode network and amygdala exclusively in older adults. Experiment 2 replicated these results in a large older adult cohort (N = 127) and additionally showed that emotion-driven changes in posterior default mode network–amygdala connectivity were associated with anxiety, rumination and negative thoughts. These findings uncover the neural dynamics of empathy-related functions in older adults and help understand its relationship to poor social stress recovery

Myeloid DLL4 Does Not Contribute to the Pathogenesis of Non-Alcoholic Steatohepatitis in Ldlr-/- Mice.

Non-alcoholic steatohepatitis (NASH) is characterized by liver steatosis and inflammation. Currently, the underlying mechanisms leading to hepatic inflammation are not fully understood and consequently, therapeutic options are poor. Non-alcoholic steatohepatitis (NASH) and atherosclerosis share the same etiology whereby macrophages play a key role in disease progression. Macrophage function can be modulated via activation of receptor-ligand binding of Notch signaling. Relevantly, global inhibition of Notch ligand Delta-Like Ligand-4 (DLL4) attenuates atherosclerosis by altering the macrophage-mediated inflammatory response. However, the specific contribution of macrophage DLL4 to hepatic inflammation is currently unknown. We hypothesized that myeloid DLL4 deficiency in low-density lipoprotein receptor knock-out (Ldlr-/-) mice reduces hepatic inflammation. Irradiated Ldlr-/- mice were transplanted (tp) with bone marrow from wild type (Wt) or DLL4f/fLysMCre+/0 (DLL4del) mice and fed either chow or high fat, high cholesterol (HFC) diet for 11 weeks. Additionally, gene expression was assessed in bone marrow-derived macrophages (BMDM) of DLL4f/fLysMCreWT and DLL4f/fLysMCre+/0 mice. In contrast to our hypothesis, inflammation was not decreased in HFC-fed DLL4del-transplanted mice. In line, in vitro, there was no difference in the expression of inflammatory genes between DLL4-deficient and wildtype bone marrow-derived macrophages. These results suggest that myeloid DLL4 deficiency does not contribute to hepatic inflammation in vivo. Since, macrophage-DLL4 expression in our model was not completely suppressed, it can't be totally excluded that complete DLL4 deletion in macrophages might lead to different results. Nevertheless, the contribution of non-myeloid Kupffer cells to notch signaling with regard to the pathogenesis of steatohepatitis is unknown and as such it is possible that, DLL4 on Kupffer cells promote the pathogenesis of steatohepatitis

Na-doped beta-tricalcium phosphate: physico-chemical and in vitro biological properties

Synthetic calcium phosphate ceramics as beta-tricalcium phosphate (Ca-3(PO4)(2); beta-TCP) are currently successfully used in human bone surgery. The aim of this work was to evaluate the influence of the presence of sodium ion in beta-TCP on its mechanical and biological properties. Five Na-doped-beta-TCP [Ca10.5-x/2Na (x) (PO4)(7), 0 <= x <= 1] microporous pellets were prepared via solid phase synthesis, and their physico-chemical data (lattice compacity, density, porosity, compressive strength, infrared spectra) denote an increase of the mechanical properties and a decrease of the solubility when the sodium content is raised. On the other hand, the in vitro study of MC3T3-E1 cell activity (morphology, MTS assay and ALP activity) shows that the incorporation of sodium does not modify the bioactivity of the beta-TCP. These results strongly suggest that Na-doped-beta-TCP appear to be good candidates for their use as bone substitutes

Physico-chemical characterization of dairy calcium phosphate industrial powders

Dairy industry recovers calcium phosphates from dairy liquids by different technologies and proposes this mineralized ingredient (under powder forms) for several applications especially for the enrichment of different food products in calcium. The objective of this study was to characterize chemically and physically 6 calcium phosphate powders coming from different international industries. All powders were rich in minerals with important quantitative variations in calcium phosphate contents depending on the powder origin. Among the powders, two were different from others because they contained less minerals and were richer in proteins (about 10% of dry matter) identified as whey proteins and lactose (about 60% of dry matter). The chemical characterization of calcium phosphate indicated that the mass ratio calcium/phosphate was closed to 0.6-0.7, except for the two powders which have higher or smaller ratios than 0.6-0.7. The profiles of dry particles size determined by laser granulometry and electron microscopy indicated also differences between powders: their sizes varied between less than one μm to several hundred μm. These size differences were attributed to a step of micronisation during the manufacture of some powders. Analyses by infrared spectroscopy (IR) and X-Ray diffraction (XRD) revealed that the precipitated calcium phosphate is a very poorly crystallized calciumdeficient apatite presenting typical PO4 vibrational bands in IR but no sharp diffraction peak. After the reconstitution of powders in water, all suspensions were at neutral pH and their zeta potentials (surface charge) were always negative (between -15 and -20mV). All these variations of physico-chemical properties between powders will be discussed to understand their functionalities with a special attention paid on their solubilities in different solutions

Relationships between diabetes-related vascular risk factors and neurodegeneration biomarkers in healthy aging and Alzheimer's disease

International audienceVascular risk factors such as hyperglycemia and platelet hyperactivation play a significant role in type 2 diabetes (T2D), a risk factor for AD. We investigated the relationships between glycemia levels, platelet indices (platelet count; mean platelet volume (MPV)) and AD neuroimaging markers in 105 cognitively unimpaired adults, including 21 amyloid-negative older adults (Aβ-neg controls), and 45 amyloid-positive patients with mild cognitive impairment or dementia (Aβ-pos patients). We assessed between-group differences on the two T2D-related vascular risk factors, then the association between blood parameters and multimodal neuroimaging (structural MRI, 18F-fluorodeoxyglucose, and 18F-florbetapir-PET) in cognitively unimpaired adults and Aβ-pos patients using multiple regressions. Compared to Aβ-neg controls, Aβ-pos patients showed lower platelet count and higher MPV. In cognitively unimpaired adults, increased glycemia levels were associated with atrophy and hypometabolism in AD-sensitive regions. In Aβ-pos patients, increased MPV was associated with entorhinal and perirhinal cortex atrophy. Subclinical but high glycemia levels in healthy individuals and MPV in AD patients are associated with neurodegeneration in AD-sensitive brain regions but not with amyloid deposition

White matter hyperintensities across the adult lifespan: relation to age, Aβ load, and cognition

International audienceAbstract Background White matter hyperintensities (WMH) are very frequent in older adults and associated with worse cognitive performance. Little is known about the links between WMH and vascular risk factors, cortical β-amyloid (Aβ) load, and cognition in cognitively unimpaired adults across the entire lifespan, especially in young and middle-aged adults. Methods One hundred and thirty-seven cognitively unimpaired adults from the community were enrolled (IMAP cohort). Participants underwent (i) a comprehensive neuropsychological assessment of episodic memory, processing speed, working memory, and executive functions; (ii) brain structural T1 and FLAIR MRI scans used for the automatic segmentation of total and regional (frontal, parietal, temporal, occipital, and corpus callosum) WMH; and (iii) a Florbetapir-PET scan to measure cortical Aβ. The relationships of total and regional WMH to age, vascular risk factors, cortical Aβ, and cognition were assessed within the whole sample, but also splitting the sample in two age groups (≤ or > 60 years old). Results WMH increased with age across the adult lifespan, i.e., even in young and middle-aged adults. Systolic blood pressure, diastolic blood pressure, and glycated hemoglobin were all associated with higher WMH before, but not after, adjusting for age and the other vascular risk factors. Higher frontal, temporal, and occipital WMH were associated with greater Aβ, but this association was no longer significant when adjusting for age and vascular risk factors. Higher total and frontal WMH were associated with worse performance in executive functions, with no interactive effect of the age group. In contrast, there was a significant interaction of the age group on the link between WMH and working memory, which was significant within the subgroup of young/middle-aged adults only. Adding cortical Aβ load in the models did not alter the results, and there was no interaction between WMH and Aβ on cognition. Conclusion WMH increased with age and were associated with worse executive functions across the adult lifespan and with worse working memory in young/middle-aged adults. Aβ load was weakly associated with WMH and did not change the relationship found between WMH and executive functions. This study argues for the clinical relevance of WMH across the adult lifespan, even in young and middle-aged adults with low WMH

White matter hyperintensities across the adult life span: Links with age, amyloid load and cognition

poster presentationInternational audienceBackground: Brain white matter hyperintensities (WMH) are frequent in older adults, including cognitively unimpaired individuals and are associated to decreased cognitive performances. The prevalence of WMH and their links with cognitive performance and with cortical β-amyloid (Aβ) burden have been rarely assessed in younger adults. The aim of this study was to assess the impact of WMH in younger and older cognitively unimpaired adults on cognitive performances and the possible interaction with cortical β-amyloid (Aβ) burden. Method: Two hundred and seventy-two cognitively unimpaired adults from the community (from the IMAP study and the Age-Well trial) were enrolled and age-stratified in 86 younger adults (YA; ≤60 years old) and 187 older adults (OA; >60 years old). All participants underwent i) a comprehensive neuropsychological assessment allowing to obtain composite scores of episodic memory, processing speed, working memory, executive functions, and global cognition; ii) brain structural T1 and FLAIR MRI scans used for automatic segmentation of WMH volumes; and iii) a Florbetapir-PET scan to measure cortical Aβ. Within each group, the relationships of total and regional WMH to age and cognition were assessed, as well as the impact of cortical Aβ on these relationships. Result: WMH increased with age in both groups but more sharply in OA than YA, particularly in the parietal lobe. Higher WMH volume was associated to worse cognitive performances in both groups. Particularly, working memory, processing speed and global cognition were negatively associated with global and regional WMH in YA and executive functions were negatively associated to occipital WMH in OA. Cortical Aβ differentially impacts the links between WMH and cognition in YA versus OA. Conclusion: WMH volume increases with age and is negatively associated to cognitive performances including in YA. This study argues for the clinical relevance of WMH even in middle age

Exposure to negative socio-emotional events induces sustained alteration of resting-state brain networks in older adults

Basic emotional functions seem well preserved in older adults. However, their reactivity to and recovery from socially negative events remain poorly characterized. To address this, we designed a 'task-rest' paradigm in which 182 participants from two independent experiments underwent functional magnetic resonance imaging while exposed to socio-emotional videos. Experiment 1 (N = 55) validated the task in young and older participants and unveiled age-dependent effects on brain activity and connectivity that predominated in resting periods after (rather than during) negative social scenes. Crucially, emotional elicitation potentiated subsequent resting-state connectivity between default mode network and amygdala exclusively in older adults. Experiment 2 replicated these results in a large older adult cohort (N = 127) and additionally showed that emotion-driven changes in posterior default mode network-amygdala connectivity were associated with anxiety, rumination and negative thoughts. These findings uncover the neural dynamics of empathy-related functions in older adults and help understand its relationship to poor social stress recovery