Gaining knowledge about methods of memory enhancement is important because it allows us to develop effective strategies and interventions to increase memory performance, optimize cognitive function, and potentially alleviate memory-related challenges such as age-related cognitive decline or memory disorders. This thesis aims to examine the influence of age on self-reported mental imagery (MI) experiences and investigate the potential effects of age and MI on memory training performance using the Method of Loci (MoL). The thesis utilizes data collected from a mobile application from a previous research project conducted at Umeå University. The main findings of this thesis indicate that older adults spent more time on encoding and retrieval tasks, suggesting a decline in cognitive processing speed. However, there was no significant decline in MI ability with age, challenging previous research and suggesting that MI ability may remain relatively stable throughout the lifespan. The findings also suggest that there was no significant correlation between higher MI ability and performance in MoL training. Participants rating themselves as having weaker MI were often achieving high levels in the MoL-training, indicating the potential utilization of alternative cognitive strategies than MI. Spending more time on encoding and retrieval tasks was associated with better performance in MoL training. The findings suggest that age-related declines in processing speed may not necessarily hinder individuals' ability to utilize MoL effectively. However, the findings challenge the idea that MI is such a decisive factor in MoL training and raise questions about which other mechanisms work together for a successful result.

The immune system is a complex network of tissues, cells and proteins which protects us against infections and invading pathogens we encounter every day. Immunosenescence refers to age-related impairments in immune function which may contribute to increased prevalence and severity of infectious disease in the elderly. How and why ageing affects the immune system is not fully understood. Using a naturally aged mouse model, work in this thesis shows that the abundance of a rare type of lymphocyte, known as NKT cells, increased across multiple immune organs. Additionally, macrophage abundance was also altered in the lymph nodes of aged mice. Invariant NKT (iNKT) cells express an invariant T cell receptor (TCR) which recognises lipids presented on the CD1d molecule. iNKT cells can be activated and respond to invading pathogens either by recognition of antigens through TCR-CD1d interactions or cytokine-dependent means. Less is known about NKT-like cells, which also express NK cell-associated surface markers, such as CD49b, but lack an invariant TCR. Data within this thesis show that both iNKT and NKT-like cell populations are abundant in the spleen and liver of aged mice. iNKT and NKT-like cells can be divided into subpopulations based on their expression of surface markers or transcription factors, and data suggests that not all subpopulations of these cells are affected by age equally. For instance, flow cytometry showed that while spleen-derived iNKT cells are significantly increased in aged mice, within the iNKT cell population the percentage representation of CD4+ cells are significantly reduced with age. Additionally, data indicates that both iNKT and NKT-like cells from aged mice show compromised responses to in vitro stimulation compared to young controls. Using bone marrow chimeras, where either young cells are reconstituted within an aged mouse or old cells are reconstituted within a young mouse, provided the opportunity to determine whether the aged environment contributes to this diminished response. Data demonstrates that the aged environment plays at least a partial role in these age-related changes to response to stimulation, however the young environment seems unable to reverse these changes. Macrophages are phagocytes which are found within all organs of the body. Studies in this thesis show that CD169+ macrophages have diminished numbers in the lymph nodes of aged mice, but this did not seem to affect the capture of the model antigen, dextran. Further studies revealed ageing affects macrophage populations differently in the different tissues within the body. For example, macrophage numbers remain constant in the spleen with ageing, but appear to increase in density in the lungs. To conclude, ageing can cause dramatic changes to the numbers and function of different cells of the immune system across multiple organs. Furthering our understanding of the ageing immune system and the underlying mechanisms which cause age-related decline in immune function is important to design strategies to improve the quality of the lives of the elderly.

Au travers des données cognitives de la cohorte stéphanoise PROOF, l’objectif de ce travail de thèse a été de déterminer quelle pouvait être la valeur pronostique de plusieurs facteurs, entre autres psychosociaux et physiologiques, d’un maintien optimal du fonctionnement cognitif avec l’âge.Le premier axe de recherche de ce travail, a mis en évidence que 70% des 632 participants âgés de 67 ans à la première évaluation cognitive de l’étude PROOF, présentaient une stabilité de leur fonctionnement cognitif après 8 ans de suivi. Le principal facteur mis en cause dans le vieillissement cognitif de cette population, que nous avons qualifié de « réussi », était, pour ces participants, d’avoir un haut niveau d’implication dans des activités sociales.Le second axe de recherche de ce travail, a mis en évidence que la dégradation de la régulation autonomique, et non la présence de facteurs de risque cardiovasculaires classiques, avait un impact négatif sur le fonctionnement mnésique des participants. Confortant ces résultats, nous avons montré que les pathologies respiratoires liées au sommeil avaient un impact négatif sur le vieillissement cognitif normal, avec un impact délétère de la fragmentation autonomique nocturne sur l’évolution des capacités mnésiques. Une préservation de l’activité du Système Nerveux Autonome (SNA) pourrait donc être une clé d’un maintien optimal des capacités mnésiques au cours du vieillissement normal.Le troisième axe de recherche de ce travail, a mis en évidence que les plaintes, qu’elles soient cognitives ou liées à la qualité de sommeil, étaient stables au décours du vieillissement normal. Nous avons pu démontrer que ce n’est pas l’âge qui génère la plainte, mais la qualité de vie et l’état anxiodépressif des personnes qui les expriment. Ceci n’est pas sans nous rappeler que le sujet, son symptôme et son histoire sont autant de déterminants du vieillissement cognitif « réussi ». Le quatrième axe de recherche de ce travail, a enfin mis en exergue que la prise en compte de la richesse des interactions sociales menées tout au long de la vie était un élément déterminant du niveau de performances dans des tâches de cognition sociale de personnes agées de 78 ans, et ce, indépendamment de la nature du fonctionnement exécutif et du niveau socioculturel. En conclusion, le vieillissement cognitif « réussi » n’est pas uniquement une vision optimiste du bien vieillir, allant contre des stéréotypes négatifs sur une perte systématique des fonctions cognitives liée à l’âge. Il s’agit d’un concept multidimensionnel qu’il convient de bien cerner si l’on veut mettre en place des stratégies efficaces susceptibles d’intervenir sur le maintien des capacités cognitives avec l’âge. Ce travail de thèse a permis de mettre en évidence l’identification de quatre facteurs déterminant du vieillissement cognitif « réussi » (et pour lesquels une intervention est possible !) qui sont : 1) le maintien des activités sociales tout au long de sa vie ; 2) la préservation d’un bon équilibre du système sympathique-parasympathique ; 3) l’absence de pathologies respiratoires liés au sommeil ; 4) la stabilité des plaintes (sommeil, cognition) exprimées avec l’âge. / The aim of this thesis was to examine cognitive performances of a large French cohort study of elderlies, i.e. the Saint Etienne PROOF-Siempre cohort, in order to assess among several factors which of them could play a prognostic role on a successful cognitive aging including physiological and psychosocial factors. In order to assess these key factors we developped several research axes frequently examining the long-term changes.The first axis of the research consider the overtime evolution of cognitive function in this population. We found that 70% of the 632 participants 67 yrs old at their inclusion in the study with or without sleep related breathing disorders had stable cognitive data 8-yr later. In this sample that we defined as having a successful cognitive aging, the predictive factor was the "high level of social activities" without any contribution of the demographic data, the hypoxemic load or classical vascular and metabolic factors.The second axis of the research we examined the influence of the autonomic nervous system activity of cognitive performances. In a sample of 916 older people, we found that a parameter reflecting the parasympathetic arm of the ANS, the baroreceptor sensitivity, affect when it was found altered the memory function without interference of other cardiovascular risk factor. These results were confirmed in a 8-yr assessment on 425 subjects of the previous sample in whom again a alteration of baroreceptor sensitity affect the long-term changes on memory function with contribution of the other examined factors. This would suggest that autonomic nervous system may also influence the memory changes with aging and assuring a more successful cognitive aging.The third axis of the research was to define how subjective cognitive and sleep complaints remain stable across time and whether subjective estimation of sleep quality may affect the changes on the subjective cognitive complaints. We found again a stability of the subjective cognitive complaint without any interference of sleep quality and aging itself, the quality of life and the presence of anxiety and depression being the most important factors. The four axis of the research examined the possible effect of the degree of social interaction developed along lifetime on the social cognition. We found in group of 100 elderly aged 78 yrs that quality of social interactions in the life-span was the key factor implicated in late social cognitive skills in the elderly without any effect of the executive function status nor the educational and intellectual level.In conclusion, we have demonstrated that in contrast to the most common recognized of a systematic loss of cognitive functions related to age healthy elderlies may have a successful cognitive aging. The "successful" cognitive aging is a multidimensional concept that should clearly identify if one wants to adopt effective strategies to maintain cognitive abilities with age. The different aspects examined in this thesis have highlighted the identification of four determinants of a "successful" cognitive aging: 1) the maintenance of social activities throughout the life; 2) the preservation of a sympathetic-parasympathetic balance of the autonomic nervous system; 3) the lack of sleep-disordered breathing; and 4) the stability of sleep and cognitive complaints generally reported in older population. The application of those strategies may help to prevent the cognitive decline in older populations.

Objective: The aim of the present study was to investigate the mechanics with which older adults activate and access different subdomains of their mental lexicons during word retrieval for picture naming. Method: Data were analyzed for 12 aging, native English speakers who performed a picture-word priming task. The auditory probe words were presented in the following conditions in relation to the picture stimuli: Identically related, strongly semantically related, weakly semantically related, strongly phonologically related, weakly phonologically related, semantically related to the strong phonological relative of the target picture label, or phonologically-related to the strong semantic relative of the target picture label. Event related potentials were used to measure picture-word priming effects. Results: Three main results were observed. First, our healthy aging adult participants evidenced strong activation of whole-word phonological representations as well as rhyme representations of target picture labels, but weakened activation of initial phoneme information. Second, they processed semantic information robustly. Finally, our participants appeared to experience phonological competition when accessing target picture labels. Conclusion: Results from this study suggest that healthy aging adults maintain efficient access to whole-word phonological representations, rhyme representations, and conceptual-semantic representations of target picture labels. However, in line with previously-reported findings, they do seem to evidence limited activation of initial phonological information on the path to picture naming.