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17 publication(s) depuis Septembre 1999:

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19/07/2018 | j gerontol a biol sci med sci   IF 4.7
Polyphenols from grape and blueberry improve episodic memory in healthy elderly with lower level of memory performance: a bicentric double-blind, randomized, placebo-controlled clinical study.
Bensalem J, Dudonne S, Etchamendy N, Pellay H, Amadieu C, Gaudout D, Dubreuil S, Paradis ME, Pomerleau S, Capuron L, Hudon C, Laye S, Desjardins Y, Pallet V

Polyphenols are promising nutritional bioactives exhibiting beneficial effect on age-related cognitive decline. The present study evaluated the effect of a polyphenol-rich extract from grape and blueberry (PEGB) on memory of healthy elderly subjects (60-70 years-old). A bicentric, randomized, double-blind, placebo-controlled trial was conducted with 215 volunteers receiving 600 mg/day of PEGB (containing 258 mg flavonoids) or a placebo for 6 months. The primary outcome was the CANTAB Paired Associate Learning (PAL), a visuospatial learning and episodic memory test. Secondary outcomes included verbal episodic and recognition memory (VRM) and working memory (SSP). There was no significant effect of PEGB on the PAL on the whole cohort. Yet, PEGB supplementation improved VRM free recall. Stratifying the cohort in quartiles based on PAL at baseline revealed a subgroup with advanced cognitive decline (decliners) who responded positively to the PEGB. In this group, PEGB consumption was also associated with a better VRM delayed recognition. In addition to a lower polyphenol consumption, the urine metabolomic profile of decliners revealed that they excreted more metabolites. Urinary concentrations of specific flavan-3-ols metabolites were associated, at the end of the intervention, with the memory improvements. Our study demonstrates that PEGB improves age-related episodic memory decline in individuals with the highest cognitive impairments.

11/2017 | Neuropsychologia   IF 2.9
Hippocampus-dependent spatial learning is associated with higher global cognition among healthy older adults.
Konishi K, Mckenzie S, Etchamendy N, Roy S, Bohbot VD

Cognitive deficits in normal aging have been associated with atrophy of the hippocampus. As such, methods to detect early dysfunction of the hippocampus have become valuable, if not indispensable, to early intervention. The hippocampus is critical for spatial memory and is among the first structures to atrophy with aging. Despite the presence of navigation deficits in aging, few studies have looked at the association between wayfinding ability, navigation strategies, general cognitive function, and hippocampal volume. In the current study we investigated whether better general cognitive function is associated with the use of hippocampal-dependent spatial strategies, better spatial memory, and increased hippocampal volume. We also investigated, within older adults, the effects of aging on spatial memory. Healthy older adults (N = 107) were tested on a virtual wayfinding task and a dual-solution navigation task that can be solved using either a hippocampal-dependent spatial strategy or a caudate nucleus-dependent response strategy. Participants were also administered the Montreal Cognitive Assessment (MoCA), a test that measures general cognition and is sensitive to dementia. A structural MRI was administered to a sub-set of participants (n = 49) and hippocampal volume was calculated using a Multiple Automatically Generated Templates (MAGeT) Brain algorithm. We found that age was negatively associated with wayfinding ability and hippocampal volume. On the wayfinding task, participants with higher MoCA scores found more target locations and travelled shorter distances. We also found a significant association between higher MoCA scores and spatial strategy use. MoCA scores, spatial memory ability, and spatial strategy use all positively correlated with a larger hippocampal volume. These results confirm that with age there is a decrease in spatial memory, which is consistent with decreased volume in the hippocampus with aging. Furthermore, better general cognitive function is associated with better wayfinding ability and increased use of hippocampal-dependent spatial strategies.

19/09/2017 | Proc Natl Acad Sci U S A   IF 9.6
Temporal binding function of dorsal CA1 is critical for declarative memory formation.
Sellami A, Al Abed AS, Brayda-Bruno L, Etchamendy N, Valerio S, Oule M, Pantaleon L, Lamothe V, Potier M, Bernard K, Jabourian M, Herry C, Mons N, Piazza PV, Eichenbaum H, Marighetto A

Temporal binding, the process that enables association between discontiguous stimuli in memory, and relational organization, a process that enables the flexibility of declarative memories, are both hippocampus-dependent and decline in aging. However, how these two processes are related in supporting declarative memory formation and how they are compromised in age-related memory loss remain hypothetical. We here identify a causal link between these two features of declarative memory: Temporal binding is a necessary condition for the relational organization of discontiguous events. We demonstrate that the formation of a relational memory is limited by the capability of temporal binding, which depends on dorsal (d)CA1 activity over time intervals and diminishes in aging. Conversely, relational representation is successful even in aged individuals when the demand on temporal binding is minimized, showing that relational/declarative memory per se is not impaired in aging. Thus, bridging temporal intervals by dCA1 activity is a critical foundation of relational representation, and a deterioration of this mechanism is responsible for the age-associated memory impairment.

The neuroimaging literature has shown consistent decreases in functional magnetic resonance imaging (fMRI) activity in the hippocampus of healthy older adults engaged in a navigation task. However, navigation in a virtual maze relies on spatial or response strategies known to depend on the hippocampus and caudate nucleus, respectively. Therefore, since the proportion of people using spatial strategies decreases with normal aging, we hypothesized that it was responsible for the observed decreases in fMRI activity in the hippocampus reported in the literature. The aim of this study was to examine the effects of aging on the hippocampus and caudate nucleus during navigation while taking into account individual navigational strategies. Young (N = 23) and older adults (N = 29) were tested using fMRI on the Concurrent Spatial Discrimination Learning Task, a radial task that dissociates between spatial and response strategies (in Stage 2) after participants reached criteria (in Stage 1). Success on Stage 2 requires that participants have encoded the spatial relationship between the target object and environmental landmarks, that is, the spatial strategy. While older adults required more trials, all participants reached criterion. fMRI results showed that, as a group, young adults had significant activity in the hippocampus as opposed to older adults who instead had significant activity in the caudate nucleus. Importantly, individual differences showed that the older participants who used a spatial strategy to solve the task had significant activity in the hippocampus. These findings suggest that the aging process involves a shift from using the hippocampus toward the caudate nucleus during navigation but that activity in the hippocampus is sustained in a subset of healthy older adults engaged in spatial strategies.

17/05/2012 | Hippocampus   IF 3.3
Juvenile, but not adult exposure to high-fat diet impairs relational memory and hippocampal neurogenesis in mice.
Boitard C, Etchamendy N, Sauvant J, Aubert A, Tronel S, Marighetto A, Laye S, Ferreira G

Increased consumption of high-fat diet (HFD) leads to obesity and adverse neurocognitive outcomes. Childhood and adolescence are important periods of brain maturation shaping cognitive function. These periods could consequently be particularly sensitive to the detrimental effects of HFD intake. In mice, juvenile and adulthood consumption of HFD induce similar morphometric and metabolic changes. However, only juvenile exposure to HFD abolishes relational memory flexibility, assessed after initial radial-maze concurrent spatial discrimination learning, and decreases neurogenesis. Our results identify a critical period of development covering adolescence with higher sensitivity to HFD-induced hippocampal dysfunction at both behavioral and cellular levels. (c) 2012 Wiley Periodicals, Inc.

04/2012 | Hippocampus   IF 3.3
Evidence for a virtual human analog of a rodent relational memory task: a study of aging and fMRI in young adults.
Etchamendy N, Konishi K, Pike GB, Marighetto A, Bohbot VD

A radial maze concurrent spatial discrimination learning paradigm consisting of two stages was previously designed to assess the flexibility property of relational memory in mice, as a model of human declarative memory. Aged mice and young adult mice with damage to the hippocampus, learned accurately Stage 1 of the task which required them to learn a constant reward location in a specific set of arms (i.e., learning phase). In contrast, they were impaired relative to healthy young adult mice in a second stage when faced with rearrangements of the same arms (i.e., flexibility probes). This mnemonic inflexibility in Stage 2 is thought to derive from insufficient relational processing by the hippocampus during initial learning (Stage 1) which favors stimulus-response learning, a form of procedural learning. This was proposed as a model of the selective declarative and relational memory decline classically described in elderly people. As a first step to examine the validity of this model, we adapted this protocol to humans using a virtual radial-maze. (1) We showed that performance in the flexibility probes in young and older adults positively correlated with performance in a wayfinding task, suggesting that our paradigm assesses relational memory. (2) We demonstrated that older healthy participants displayed a deficit in the performance of the flexibility probes (Stage 2), similar to the one previously seen in aged mice. This was associated with a decline in the wayfinding task. (3) Our fMRI data in young adults confirmed that hippocampal activation during early discrimination learning in Stage 1 correlated with memory flexibility in Stage 2, whereas caudate nucleus activation in Stage 1 negatively correlated with subsequent flexibility. By enabling relational memory assessment in mice and humans, our radial-maze paradigm provides a valuable tool for translational research.

2012 | Curr Top Behav Neurosci   IF 2.7
Studying the impact of aging on memory systems: contribution of two behavioral models in the mouse.
Marighetto A, Brayda-Bruno L, Etchamendy N

In the present chapter, we describe our own attempts to improve our understanding of the pathophysiology of memory in aging. First, we tried to improve animal models of memory degradations occurring in aging, and develop common behavioral tools between mice and humans. Second, we began to use these behavioral tools to identify the molecular/intracellular changes occurring within the integrate network of memory systems in order to bridge the gap between the molecular and system level of analysis. The chapter is divided into three parts (i) modeling aging-related degradation in declarative memory (DM) in mice, (ii) assessing the main components of working memory (WM) with a common radial-maze task in mice and humans and (iii) studying the role of the retinoid cellular signaling path in aging-related changes in memory systems.

Multiple memory systems are involved in parallel processing of spatial information during navigation. A series of studies have distinguished between hippocampus-dependent 'spatial' navigation, which relies on knowledge of the relationship between landmarks in one's environment to build a cognitive map, and habit-based 'response' learning, which requires the memorization of a series of actions and is mediated by the caudate nucleus. Studies have demonstrated that people spontaneously use one of these two alternative navigational strategies with almost equal frequency to solve a given navigation task, and that strategy correlates with functional magnetic resonance imaging (fMRI) activity and grey matter density. Although there is evidence for experience modulating grey matter in the hippocampus, genetic contributions may also play an important role in the hippocampus and caudate nucleus. Recently, the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene has emerged as a possible inhibitor of hippocampal function. We have investigated the role of the BDNF Val66Met polymorphism on virtual navigation behaviour and brain activation during an fMRI navigation task. Our results demonstrate a genetic contribution to spontaneous strategies, where 'Met' carriers use a response strategy more frequently than individuals homozygous for the 'Val' allele. Additionally, we found increased hippocampal activation in the Val group relative to the Met group during performance of a virtual navigation task. Our results support the idea that the BDNF gene with the Val66Met polymorphism is a novel candidate gene involved in determining spontaneous strategies during navigation behaviour.

02/01/2008 | J Neurosci   IF 6.1
Retinoid hyposignaling contributes to aging-related decline in hippocampal
Mingaud F, Mormede C, Etchamendy N, Mons N, Niedergang B, Wietrzych M, Pallet V, Jaffard R, Krezel W, Higueret P, Marighetto A

An increasing body of evidence indicates that the vitamin A metabolite retinoic

2007 | Hippocampus   IF 3.3
The hippocampus plays a critical role at encoding discontiguous events for
Mingaud F, Le Moine C, Etchamendy N, Mormede C, Jaffard R, Marighetto A

The hypothesis that hippocampal activity at encoding is causally related to