Résilience et vieillissement cognitif : une approche de modération en neuro-imagerie structurelle et fonctionnelle

Many changes to the brain occur in normal aging, both structurally and functionally. These changes most often result in a certain deterioration of cognitive functioning, and thus affect the quality of life of the elderly. It appears, however, that some people are relatively spared and manage to maintain a comparatively high level of cognitive functioning despite advancing in age. In the presence of an acceleration of population aging, there is a striking need to understand the factors and neurobiological mechanisms that may contribute to this better resilience to the effects of aging on the brain and on cognition. Although several models have attempted to account for this phenomenon, the understanding of the mechanisms that underpin it is still relatively incomplete. The main objective of this thesis was to expose the neurobiological correlates associated with a better resilience to the effects of normal aging on the brain and cognition, through structural (MRI) and functional magnetic resonance imaging (fMRI). This thesis contains four articles. The intention of the first article (Chapter II) was to synthesize knowledge about the mechanisms involved in the resilience against the degenerative effects of normal aging on cognition. In this literature review, we were interested in the two main models attempting to account for this protective phenomenon: the brain reserve and cognitive reserve. Examining the empirical literature leads to the conclusion that better resilience might be based on both structural and functional brain differences, and therefore that the two proposed models could make an independent contribution to the resilience phenomenon. In addition, we hypothesize that the correlates of resilience are very similar to the brain differences associated with cognitive training. The following three articles are empirical articles which focus on working memory, a function that declines with age but shows significant inter-individual differences. The purpose of the second article (Chapter III) was to investigate the relationship between education, a well-established reserve proxy, and the regional volume of gray matter, as well as between education and brain activation during a working memory task in cognitively healthy elderly participants. Results indicate that higher years of education are associated with lower age-related loss of volume in the frontal and parietal areas, as well as greater age-related activation in some prefrontal regions that are part of the working memory network. The third study (Chapter IV) sought to examine whether functional education-related brain differences are compatible with neuronal efficiency and/or flexibility mechanisms. It further aimed to examine the "protective" effect of these functional differences on working memory performance. The results suggest that the two proposed mechanisms would be associated with a better preservation of working memory in the face of the effects of age, but that their respective involvement would depend on the level of the task requirement. Finally, the objective of the fourth study (Chapter V) was to first test the relationship between engagement in a stimulating lifestyle and white matter integrity maintaining. Then, the study aimed to examine whether greater white matter integrity decreased the impact of age on working memory. The results of the study suggest that a more stimulating lifestyle would be associated with a lesser age-related white matter lesions volume, and that this smaller white matter lesions volume would in turn be associated with better working memory performance.

Keyphrases: Compensation, Resilience, Cognitive reserve, Brain reserve, Brain maintenance, Compensation, Normal aging, Magnetic resonance imaging (MRI), Functional magnetic resonance imaging (fMRI), Moderation analysis