Alcohol use disorder is a chronic disease characterized by an inappropriate pattern of drinking, resulting in negative consequences for the individual's physical, mental and social health. Korsakoff's syndrome is a complication of alcohol use disorder and is characterized by severe memory and executive deficits. The fronto-cerebellar and Papez circuits are structurally affected in patients with alcohol use disorder with and without Korsakoff’s syndrome. The first objective of the present study was to measure the effect of chronic and excessive alcohol consumption on resting-state functional connectivity of these two functional brain networks. The second objective was to identify, for the first time, resting-state functional connectivity abnormalities specific to amnesic patients with Korsakoff’s syndrome. In the present study, a neuropsychological assessment and a resting-state functional magnetic resonance imaging examination were conducted in 31 healthy controls (43.6 ± 6.1 years) and 46 patients (46.6 ± 9.1 years) with alcohol use disorder including 14 patients with Korsakoff’s syndrome (55.5 ± 5.3 years) to examine the effect of chronic and heavy alcohol consumption on functional connectivity of the fronto-cerebellar and the Papez circuits at rest and the specificity of functional connectivity changes in Korsakoff’s syndrome compared to alcohol use disorder without Korsakoff’s syndrome. The resting-state functional connectivity analyses focused on the nodes of the fronto-cerebellar and Papez circuits and combined region of interest and graph theory approaches, and whether these alterations are associated with the neuropsychological profile. In patients pooled together compared to controls, lower global efficiency was observed in the fronto-cerebellar circuit. In addition, certain regions of the fronto-cerebellar and Papez circuits were functionally hyperconnected at rest, which positively correlated with executive functions. Patients with Korsakoff’s syndrome showed lower resting-state functional connectivity, lower local and global efficiency within the Papez circuit compared to those without Korsakoff’s syndrome. Resting-state functional connectivity positively correlated with several cognitive scores in patients with Korsakoff’s syndrome. The fronto-cerebellar and Papez circuits, two normally well-segregated networks, are functionally altered by alcohol use disorder. The Papez circuit attempts to compensate for deficits in the fronto-cerebellar circuit, albeit insufficiently as evidenced by patients’ overall lower cognitive performance. Korsakoff’s syndrome is characterized by altered functional connectivity in the Papez circuit known to be centrally involved in memory.

Background: Cognitive aging is highly heterogeneous, not only in performance but also in how individuals perceive their own aging. Such self-perceptions may shape emotional reactions and adaptation to memory difficulties, yet little is known about their organization in patients referred to a memory clinic for a first diagnostic consultation. The primary aim of this study was to identify the internal configuration of self-perceptions of aging in such patients. A secondary aim was to compare these patterns with those observed in older adults recruited in a research unit of experimental psychology, who reported subjective complaints but had no medical referral. Methods: In total, 130 memory clinic patients and 84 laboratory participants completed, prior to the same neuropsychological testing, a psychosocial questionnaire assessing four domains: self-perceptions of memory deficits, attitudes toward aging, aging stereotypes, and multiple facets of subjective age. Network analysis was applied to examine how these variables were interrelated and to determine their relative importance in each group. Results: Across both samples, network analyses revealed distinct organizational patterns. Patients showed a unified representational system characterized by more positive associations and centered on subjective age variables. By contrast, the laboratory group showed a two-cluster network with more negative connections, organized around negative aging stereotypes. Conclusions: These findings provide novel insights into the psychosocial profile of memory clinic patients, highlighting the added value of network approaches for capturing the interrelations among key self-representations of aging and memory, and for informing and contextualizing clinical evaluation.

Background: Cognitive aging is highly heterogeneous, not only in performance but also in how individuals perceive their own aging. Such self-perceptions may shape emotional reactions and adaptation to memory difficulties, yet little is known about their organization in patients referred to a memory clinic for a first diagnostic consultation. The primary aim of this study was to identify the internal configuration of self-perceptions of aging in such patients. A secondary aim was to compare these patterns with those observed in older adults recruited in a research unit of experimental psychology, who reported subjective complaints but had no medical referral. Methods: In total, 130 memory clinic patients and 84 laboratory participants completed, prior to the same neuropsychological testing, a psychosocial questionnaire assessing four domains: self-perceptions of memory deficits, attitudes toward aging, aging stereotypes, and multiple facets of subjective age. Network analysis was applied to examine how these variables were interrelated and to determine their relative importance in each group. Results: Across both samples, network analyses revealed distinct organizational patterns. Patients showed a unified representational system characterized by more positive associations and centered on subjective age variables. By contrast, the laboratory group showed a two-cluster network with more negative connections, organized around negative aging stereotypes. Conclusions: These findings provide novel insights into the psychosocial profile of memory clinic patients, highlighting the central integrative role of subjective age in integrating emotional responses, aging beliefs and perceptions of memory difficulties, and underline the value of network approaches in capturing heterogeneity in cognitive aging.

L’un des objectifs de la première partie de la thèse était de mieux appréhender les substrats neuronaux associés au déclin de la mémoire prospective time-based dans le vieillissement sain. Le second objectif a été d’explorer le déclin de la mémoire prospective dans la maladie d’Alzheimer à l’aide d’une tâche de mémoire prospective en réalité virtuelle. Dans une seconde partie, ce travail a porté sur les effets négatifs des stéréotypes du vieillissement, en situation clinique, lors des bilans neuropsychologiques. Les deux premières études mettent en évidence une altération des faisceaux de substance blanche et des réseaux de connectivité au repos associés au déclin de la mémoire prospective time-based. Le déclin observé dans le vieillissement sain est associé à des altérations au niveau du réseau fronto-pariétal impliqué dans les processus automatiques et contrôlés. Les résultats de la troisième étude suggèrent l’atteinte généralisée de la mémoire prospective chez les patients Alzheimer liée à des troubles authentiques dans les processus mnésiques. Enfin, cette thèse a mis en évidence pour la première fois, un effet de la menace du stéréotype en milieu clinique chez des patients venant pour une première consultation neuropsychologique. Il sera important dans la clinique future de porter attention à l’effet implicite des facteurs psychosociaux au sein des bilans. A l’inverse, la recherche doit également prendre en compte ce biais dans les protocoles expérimentaux. Il semble important que chacun à son échelle modifie son comportement afin d’endiguer la propagation des stéréotypes négatifs liés à l’âge.