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We examined the association between preclinical Alzheimer's disease (AD) and undergoing anesthesia and surgery ("surgery" henceforth) in a cohort of elderly individuals with a subjective cognitive decline (SCD).Individuals with SCD (N = 268) were enrolled in a longitudinal follow-up study. Participants underwent comprehensive yearly cognitive evaluation for a period of 4 years. Brain amyloid load and glucose metabolism were studied by 18F-Florbetapir and Fluorodeoxyglucose positron emission tomography (PET) at baseline and after two years of follow-up. Exposure to surgery was systematically assessed during the first two years of follow-up. The association between surgery, cognition and AD markers was evaluated using generalized linear mixed models for cognition and linear models for neuroimaging markers.Sixty-five participants (24.25%) underwent surgery during the first year of follow-up, and 43 (16.04%) during the second year. Undergoing surgery had no overall impact on cognition over 4 years of follow-up nor on amyloid load and brain metabolism at two years of follow-up. However, a second step analysis revealed a small but significant association between undergoing surgery and a subtle decline in executive functions such as mental flexibility and divided attention (TMT B-A), in participants with greater amyloid load at baseline (Cohen's f2 = 0.01, multiple comparison corrected p 0.001). Highly educated participants with surgery had significantly decreased metabolism over two years, when compared to low educated participants (Cohen's f2 = 0.04, p = 0.031).Our results suggest that surgery is associated with an increased risk of subtle cognitive decline after surgery, in the cognitively healthy elderly at risk for AD.

Disinhibition is a core symptom in several neurodegenerative diseases such as behavioural variant frontotemporal dementia (bvFTD), and is a major source of stress for patients and caregivers. In a literature review, we discussed inhibition deficits in dementia, by describing current tests available to assess disinhibition, its manifestations across diseases and latest findings about neural correlates. Etiology and neural correlates of disinhibition remain poorly known, especially for behavioural disinhibition. This neuropsychiatric symptom is commonly assessed as a single component on the basis of questionnaires completed by caregivers. This practice raises methodological concerns about the lack of objectivity, ecological validity and specificity of these tools, which may explain the diversity of neural correlates found in the literature. In this context, we explored behavioural inhibition troubles in bvFTD patients by distinguishing three subtypes of disinhibition – compulsivity, impulsivity and social disinhibition – by combining three approaches: an ethological study under ecological condition, a neuropsychological assessment and structural imaging. First, we described manifestation of disinhibition and associated neuropsychological deficits, before proposing ways for non-pharmacological management based on their context of occurrence. We then highlighted possibility of distinguishing different clinico-anatomical profiles of bvFTD patients on the basis of behavioural observation. Finally, we identified distinct neural networks underlying compulsivity and social disinhibition. These results are promising for detection and management of disinhibition in clinical practice, helping to better stratify patients for future therapeutic trials. Investigation in another neurological condition such as Alzheimer’s disease would also help to refine differential diagnoses based on disinhibition and would improve patient care management.; La désinhibition est un trouble présent dans plusieurs pathologies neurodégénératives, telles que la démence fronto-temporale de type comportemental (DFTc), et constitue une source de stress majeur dans la vie quotidienne des patients et de leurs aidants. Dans une revue de la littérature, nous avons décrit les troubles de l’inhibition dans les démences, en détaillant les tests permettant de les évaluer, leurs manifestations et les corrélats neuronaux associés. Il s’avère que l’étiologie et les substrats neuronaux de la désinhibition restent mal élucidés, particulièrement pour la désinhibition comportementale. Ce symptôme neuropsychiatrique est classiquement évalué comme une unique composante sur la base de questionnaires renseignés par les aidants. Cette pratique soulève des interrogations méthodologiques concernant le manque d’objectivité, de validité écologique, et de spécificité de ces outils, pouvant expliquer la diversité de corrélats neuronaux retrouvés dans la littérature. Dans ce contexte, nous avons exploré les troubles de l’inhibition comportementale chez les patients DFTc en distinguant trois sous-catégories de désinhibition – la compulsivité, l’impulsivité et la désinhibition sociale – en combinant trois approches : une étude comportementale éthologique en situation écologique, un bilan neuropsychologique et de l’imagerie structurelle. Dans un premier temps, nous avons décrit la manifestation de ces troubles et les déficits neuropsychologiques associés, avant de proposer des pistes de prise en charge non pharmacologique d’après leur contexte d’occurrence. Nous avons ensuite souligné la possibilité de distinguer différents profils clinico-anatomiques de patients DFTc sur la base des observations comportementales de la désinhibition. Enfin, nous avons mis en évidence des réseaux neuronaux distincts sous-tendant la compulsivité et la désinhibition sociale. Ces résultats sont prometteurs pour la détection et la prise en charge de la désinhibition en pratique clinique, contribuant à mieux stratifier les patients pour les essais thérapeutiques à venir. L’investigation de ces troubles dans d’autres pathologies, telles que la maladie d’Alzheimer, permettrait de surcroît d’affiner les diagnostics différentiels sur la base de la désinhibition et d’améliorer ainsi la prise en charge de ces patients.