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Influence of acute physical exercise on spatial memory in young adults with and without the APOE-e4 allele

English title Influence of acute physical exercise on spatial memory in young adults with and without the APOE-e4 allele
Applicant Marin Bosch Blanca
Number 184161
Funding scheme Doc.Mobility
Research institution NTNU Norwegian University of Science and Technology
Institution of higher education Institution abroad - IACH
Main discipline Neurophysiology and Brain Research
Start/End 01.03.2019 - 31.08.2019
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Keywords (4)

memory; Alzheimer's disease; grid cells; exercise

Lay Summary (French)

Lead
La maladie d’Alzheimer est une maladie neurodégénérative qui affecte environ 50 millions de personnes dans le monde. Quelles personnes vont avoir Alzheimer en fin de vie n’est pas connu. Certaines personnes sont porteurs d’un allèle (apo e4) associé à une prévalence de développer Alzheimer plus importante que la population générale. Par ailleurs, l’activité physique a un effet positif sur la mémoire en particulier au cours du vieillissement. Ce projet va évaluer l’impact d’une séance d’exercice physique à intensité modérée sur la mémoire spatiale de personnes jeunes qui sont à haut risque de développer Alzheimer au cours de leur vie.
Lay summary

Contenu et objectifs du travail de recherche

Ce projet va mesurer l’effet d’une séance d’exercice physique sur la mémoire de deux groupes de volontaires, un groupe à haut risque et un groupe à faible risque de développer Alzheimer. L’objectif du projet est d’évaluer si l’exercice physique peut sélectivement favoriser la mémoire spatiale des personnes à haut risque et ainsi compenser les premiers déficits qui ont été trouvés chez ces personnes dès le jeune âge.

Contexte scientifique et social du projet de recherche

L’inactivité physique est un des plus importants facteurs de risque modifiables de la maladie d’Alzheimer. C’est pourquoi, démontrer l’efficacité de l’exercice physique pour prévenir des symptômes précoces de démence engendrerait des conséquences bénéfiques majeures pour les politiques de santé publique. Vu la prévalence de la maladie d’Alzheimer dans la population générale conjugué au vieillissement de nos sociétés et au manque d’exercice physique à tout âge, il est d’importance cruciale d’adresser ces questions de santé publique.

Direct link to Lay Summary Last update: 16.01.2019

Responsible applicant and co-applicants

Collaboration

Group / person Country
Types of collaboration
Prof. Aurelien Thomas' lab Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Doeller lab Norway (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Prof. Guido Ferretti's lab Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure

Abstract

The goal for this fellowship is to acquire the methodology for the analysis of grid-cell representations in human fMRI data. This methodology has been developed and validated by Prof. Doeller’s lab in numerous high impact publications [1, 2] at the Kavli Institute of Systems Neuroscience, where I will be staying. The collaboration with the Doeller lab has been established for the third and last project of my PhD thesis.Neurodegenerative diseases, especially Alzheimer’s disease (AD), affect cognitive functions primarily memory. Research has demonstrated that spatial memory, or remembering where things are, is a key element where cognitive deficits can be identified first. Recently, Prof. Doeller’s team has demonstrated that healthy young adults at increased genetic risk of developing AD in later life (carriers of the APOE-e4 allele) have impaired spatial navigation strategies and significantly worse representations of a type of cells involved in spatial navigation, namely grid cells located in the entorhinal cortex [2]. That said, physical exercise (both regular and acute) has been attracting attention for its beneficial role in cognitive functions [3]. Exercise promotes hippocampal neurogenesis and plasticity, thus enhancing learning and memory (including spatial) functions [4, 5]. According to recent reports, physical exercise may prevent cognitive decline in mild cognitive impairment or early AD [6]. Whether physical exercise from a young age may have a protective effect against future spatial memory deficits remains unknown. In the present and third project of my thesis, I will investigate whether acute physical exercise can strengthen spatial and associative memory performance in healthy young adults with and without the APOE-e4 allele. My previous research demonstrated that moderate intensity exercise (rather than high intensity exercise) had the strongest impact on memory functions. We also showed that these exercise-dependent memory improvements involved changes in cerebral vasomotion during exercise), in hippocampal responses, and in the levels of certain biomarkers affecting neuronal plasticity (i.e. BDNF and anandamide). Based on these previous results, and together with Prof. Doeller, we designed the present project aiming at characterizing the effects of acute, moderate intensity exercise (compared to rest) on spatial memory in young adults with and without the APOE-e4 allele. This project combines our expertise on exercise-dependent neural plasticity and the Doeller’s methodology for testing grid-cell representations in humans. Specifically, we are in charge of setting up the exercise protocol, monitoring physical exercise via near infrared spectroscopy (NIRS), as well as collecting and analyzing biomarkers involved in plasticity and neurogenesis (BDNF and anandamide), which we showed are modulated by physical exercise. Our collaborators in Norway taught me how to implement their grid cell task and will teach me how to analyze grid-cell representations both behaviorally and in fMRI. Our hypothesis is that physical exercise will significantly benefit both carriers and non-carriers of the e4 allele, however we additionally expect that the magnitude of the benefit should be enhanced for APOE- e4 carriers compensating for early deficits.. The results of the project may shed light on a possible strategy to counteract the impairments associated with this allele and to investigate the extent of this counteraction. This fellowship will allow me to fulfill my thesis goals and will be instrumental in my training and my future career.
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