Grey matter atrophy in prodromal stage of dementia with Lewy bodies and Alzheimer’s disease

BACKGROUND: Little is known about the patterns of brain atrophy in prodromal dementia with Lewy bodies (pro-DLB). METHODS: In this study, we used SPM8 with diffeomorphic anatomical registration through exponentiated lie algebra to measure grey matter (GM) volume and investigate patterns of GM atrophy in pro-DLB (n = 28) and prodromal Alzheimer's disease (pro-AD) (n = 27) and compared and contrasted them with those in elderly control subjects (n = 33) (P ≤ 0.05 corrected for family-wise error). RESULTS: Patients with pro-DLB showed diminished GM volumes of bilateral insulae and right anterior cingulate cortex compared with control subjects. Comparison of GM volume between patients with pro-AD and control subjects showed a more extensive pattern, with volume reductions in temporal (hippocampi and superior and middle gyri), parietal and frontal structures in the former. Direct comparison of prodromal groups suggested that more atrophy was evident in the parietal lobes of patients with pro-AD than patients with pro-DLB. In patients with pro-DLB, we found that visual hallucinations were associated with relative atrophy of the left cuneus. CONCLUSIONS: Atrophy in pro-DLB involves the insulae and anterior cingulate cortex, regions rich in von Economo neurons, which we speculate may contribute to the early clinical phenotype of pro-DLB.This study was funded by Appel à Projet Interne (API) of the University Hospital of Strasbourg, Alsace Alzheimer 67, Fondation Université de Strasbourg and famille Jean Amrhein, and Projet Hospitalier de Recherche Clinique (PHRC) inter-régional (IDRCB 2012-A00992-41). The work was also supported by the following: the Newcastle Healthcare Charity (BH0070250); Academy of Medical Sciences, Wellcome Trust Starter Grants scheme for Clinical Lecturers (BH090112 to JPT); Wellcome Intermediate Clinical Fellowship (BH083281 to JPT); National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre in Ageing and Chronic Disease and Biomedical Research Unit in Lewy Body Dementia, based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University; NIHR Dementia Biomedical Research Unit at Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge

A Missense Mutation in PPP1R15B Causes a Syndrome Including Diabetes, Short Stature, and Microcephaly.

Dysregulated endoplasmic reticulum stress and phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) are associated with pancreatic β-cell failure and diabetes. Here, we report the first homozygous mutation in the PPP1R15B gene (also known as constitutive repressor of eIF2α phosphorylation [CReP]) encoding the regulatory subunit of an eIF2α-specific phosphatase in two siblings affected by a novel syndrome of diabetes of youth with short stature, intellectual disability, and microcephaly. The R658C mutation in PPP1R15B affects a conserved amino acid within the domain important for protein phosphatase 1 (PP1) binding. The R658C mutation decreases PP1 binding and eIF2α dephosphorylation and results in β-cell apoptosis. Our findings support the concept that dysregulated eIF2α phosphorylation, whether decreased by mutation of the kinase (EIF2AK3) in Wolcott-Rallison syndrome or increased by mutation of the phosphatase (PPP1R15B), is deleterious to β-cells and other secretory tissues, resulting in diabetes associated with multisystem abnormalities.This work was supported by the European Union 7th Framework Programme (project BetaBat), the Actions de Recherche Concertées de la Communauté Française, and Fonds National de la Recherche Scientifique (FNRS), Belgium, and by grants from the Agence Nationale pour la Recherche (ANR-09-GENO-021), the European Foundation for the Study of Diabetes/JDRF/Novo Nordisk, the Assistance Publique-Hôpitaux de Paris Programme Hospitalier de Recherche Clinique (DIAGENE), the GIS Maladies Rares, and the Wellcome Trust (084812/Z/08/Z). A.T.H. is a Wellcome Trust and National Institute for Health Research senior investigator, and D.R. is a Wellcome Trust Principal Research Fellow. B.A. was supported by an European Molecular Biology Organization Short-Term Fellowship and an FNRS-FRIA fellowship. M.I.-E. is a scientific collaborator of the FNRS. M.D. was supported by a doctoral fellowship from the Ministère de l’Education Nationale, de l’Enseignement Supérieur et de la Recherche, France.This is the author accepted manuscript. The final version is available from the American Diabetes Association via http://dx.doi.org/10.2337/db15-047

Does Culture Shape Our Understanding of Others’ Thoughts and Emotions? An Investigation Across 12 Countries

Q2Q2Measures of social cognition have now become central in neuropsychology, being essential for early and differential diagnoses, follow-up, and rehabilitation in a wide range of conditions. With the scientific world becoming increasingly interconnected, international neuropsychological and medical collaborations are burgeoning to tackle the global challenges that are mental health conditions. These initiatives commonly merge data across a diversity of populations and countries, while ignoring their specificity. Objective: In this context, we aimed to estimate the influence of participants’ nationality on social cognition evaluation. This issue is of particular importance as most cognitive tasks are developed in highly specific contexts, not representative of that encountered by the world’s population. Method: Through a large international study across 18 sites, neuropsychologists assessed core aspects of social cognition in 587 participants from 12 countries using traditional and widely used tasks. Results: Age, gender, and education were found to impact measures of mentalizing and emotion recognition. After controlling for these factors, differences between countries accounted for more than 20% of the variance on both measures. Importantly, it was possible to isolate participants’ nationality from potential translation issues, which classically constitute a major limitation. Conclusions: Overall, these findings highlight the need for important methodological shifts to better represent social cognition in both fundamental research and clinical practice, especially within emerging international networks and consortia.https://orcid.org/0000-0001-9422-3579https://orcid.org/0000-0001-6529-7077Revista Internacional - IndexadaA2N

Sex differences in brain atrophy in dementia with Lewy bodies

Publisher Copyright: © 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.INTRODUCTION: Sex influences neurodegeneration, but it has been poorly investigated in dementia with Lewy bodies (DLB). We investigated sex differences in brain atrophy in DLB using magnetic resonance imaging (MRI). METHODS: We included 436 patients from the European-DLB consortium and the Mayo Clinic. Sex differences and sex-by-age interactions were assessed through visual atrophy rating scales (n = 327; 73 ± 8 years, 62% males) and automated estimations of regional gray matter volume and cortical thickness (n = 165; 69 ± 9 years, 72% males). RESULTS: We found a higher likelihood of frontal atrophy and smaller volumes in six cortical regions in males and thinner olfactory cortices in females. There were significant sex-by-age interactions in volume (six regions) and cortical thickness (seven regions) across the entire cortex. DISCUSSION: We demonstrate that males have more widespread cortical atrophy at younger ages, but differences tend to disappear with increasing age, with males and females converging around the age of 75. Highlights: Male DLB patients had higher odds for frontal atrophy on radiological visual rating scales. Male DLB patients displayed a widespread pattern of cortical gray matter alterations on automated methods. Sex differences in gray matter measures in DLB tended to disappear with increasing age.Peer reviewe

Mémoire autobiographique et self dans la maladie d'Alzheimer : étude neuropsychologique et en neuro-imagerie

The present study aimed at studying autobiographical memory (AbM) in patients at early stages of Alzheimer’s disease, as well as at analyzing the link between AbM and the Self components (as defined by Prebble et al., 2013), and finally, at investigating its neuro-anatomical correlates. The results we obtained confirmed AbM is damaged in patients with regards to episodic and emotional components, whatever the age of the memory. The deficit in episodic memory was associated with medial temporal lobe atrophy, with the left hippocampus seemingly involved in the temporal context of the memories and the right amygdala in the emotional component. Conversely, specificity of remaining emotional memories was relatively preserved, as well as semanticized memories, which rely on the temporal neocortex. In the context of the Self more generally, our results highlight a relationship between the conceptual-Self and autobiographical memories, through semanticization and integration processes, which allow the formation of the most abstracted forms of self-representations. Moreover, the subjective sense of Self appears as a prerequisite to all other Self components. Based upon a case study and a volumetric group study, we were able to show that the implication of the medial prefrontal cortex is common to all Self components, suggesting its key role for the subjective sense of Self. Our results point to a potential rehabilitation therapy based on reinforcing self-defining memories to strengthen the Self. This work will be completed by the study of functional and anatomical networks sustaining the Self.L’objectif de ce travail était d’étudier la mémoire autobiographique (MAb) aux stades débutants de la maladie d’Alzheimer et d’analyser le lien avec le Self défini selon le modèle de Prebble et collaborateurs. (2013) et en investiguant les substrats neuro-anatomiques. Notre étude a confirmé qu’il existait une altération de la MAb chez les patients atteints de maladie d’Alzheimer, dans sa composante épisodique et émotionnelle, quelle que soit l’ancienneté des souvenirs. Nous avons pu rattacher ce déficit épisodique à l’atrophie des régions temporales internes et en suggérer l’implication de l’hippocampe gauche dans le contexte temporel des souvenirs et de l’amygdale droite dans la composante émotionnelle. En revanche, il existait une relative préservation du niveau des détails des souvenirs émotionnels résiduels, et surtout, des souvenirs sémantisés, ces derniers étant supportés par le néocortex temporal. Concernant le Self de façon plus générale, les résultats mettent en évidence un lien entre Self-conceptuel et MAb, par le biais des processus de sémantisation et d’intégration des souvenirs qui permettent de former des représentations abstraites à partir des expériences vécues. Par ailleurs, nous avons également montré que le sens subjectif de soi est inhérent à toutes les autres composantes du Self. Par l’étude d’un cas unique et d’imagerie volumétrique de groupe, le cortex préfrontal médian a été mis en évidence comme substrat commun à toutes les composantes du Self, suggérant un rôle clé de cette structure pour supporter le sens subjectif de soi. Ces résultats ouvrent des pistes de remédiation par la réminiscence basée sur les mécanismes de sémantisation, d’intégration et sur les aspects émotionnels, au centre desquels se trouvent les souvenirs définissant-le-soi. Aussi notre étude engage-t-elle à analyser ces composantes du Self au sein de réseaux, en connectivité fonctionnelle et anatomique

Autobiographical memory and self in Alzheimer’s disease : neuropsychological and neuroimaging study

L’objectif de ce travail était d’étudier la mémoire autobiographique (MAb) aux stades débutants de la maladie d’Alzheimer et d’analyser le lien avec le Self défini selon le modèle de Prebble et collaborateurs. (2013) et en investiguant les substrats neuro-anatomiques. Notre étude a confirmé qu’il existait une altération de la MAb chez les patients atteints de maladie d’Alzheimer, dans sa composante épisodique et émotionnelle, quelle que soit l’ancienneté des souvenirs. Nous avons pu rattacher ce déficit épisodique à l’atrophie des régions temporales internes et en suggérer l’implication de l’hippocampe gauche dans le contexte temporel des souvenirs et de l’amygdale droite dans la composante émotionnelle. En revanche, il existait une relative préservation du niveau des détails des souvenirs émotionnels résiduels, et surtout, des souvenirs sémantisés, ces derniers étant supportés par le néocortex temporal. Concernant le Self de façon plus générale, les résultats mettent en évidence un lien entre Self-conceptuel et MAb, par le biais des processus de sémantisation et d’intégration des souvenirs qui permettent de former des représentations abstraites à partir des expériences vécues. Par ailleurs, nous avons également montré que le sens subjectif de soi est inhérent à toutes les autres composantes du Self. Par l’étude d’un cas unique et d’imagerie volumétrique de groupe, le cortex préfrontal médian a été mis en évidence comme substrat commun à toutes les composantes du Self, suggérant un rôle clé de cette structure pour supporter le sens subjectif de soi. Ces résultats ouvrent des pistes de remédiation par la réminiscence basée sur les mécanismes de sémantisation, d’intégration et sur les aspects émotionnels, au centre desquels se trouvent les souvenirs définissant-le-soi. Aussi notre étude engage-t-elle à analyser ces composantes du Self au sein de réseaux, en connectivité fonctionnelle et anatomique.The present study aimed at studying autobiographical memory (AbM) in patients at early stages of Alzheimer’s disease, as well as at analyzing the link between AbM and the Self components (as defined by Prebble et al., 2013), and finally, at investigating its neuro-anatomical correlates. The results we obtained confirmed AbM is damaged in patients with regards to episodic and emotional components, whatever the age of the memory. The deficit in episodic memory was associated with medial temporal lobe atrophy, with the left hippocampus seemingly involved in the temporal context of the memories and the right amygdala in the emotional component. Conversely, specificity of remaining emotional memories was relatively preserved, as well as semanticized memories, which rely on the temporal neocortex. In the context of the Self more generally, our results highlight a relationship between the conceptual-Self and autobiographical memories, through semanticization and integration processes, which allow the formation of the most abstracted forms of self-representations. Moreover, the subjective sense of Self appears as a prerequisite to all other Self components. Based upon a case study and a volumetric group study, we were able to show that the implication of the medial prefrontal cortex is common to all Self components, suggesting its key role for the subjective sense of Self. Our results point to a potential rehabilitation therapy based on reinforcing self-defining memories to strengthen the Self. This work will be completed by the study of functional and anatomical networks sustaining the Self

Autobiographical memory and self in Alzheimer’s disease : neuropsychological and neuroimaging study

L’objectif de ce travail était d’étudier la mémoire autobiographique (MAb) aux stades débutants de la maladie d’Alzheimer et d’analyser le lien avec le Self défini selon le modèle de Prebble et collaborateurs. (2013) et en investiguant les substrats neuro-anatomiques. Notre étude a confirmé qu’il existait une altération de la MAb chez les patients atteints de maladie d’Alzheimer, dans sa composante épisodique et émotionnelle, quelle que soit l’ancienneté des souvenirs. Nous avons pu rattacher ce déficit épisodique à l’atrophie des régions temporales internes et en suggérer l’implication de l’hippocampe gauche dans le contexte temporel des souvenirs et de l’amygdale droite dans la composante émotionnelle. En revanche, il existait une relative préservation du niveau des détails des souvenirs émotionnels résiduels, et surtout, des souvenirs sémantisés, ces derniers étant supportés par le néocortex temporal. Concernant le Self de façon plus générale, les résultats mettent en évidence un lien entre Self-conceptuel et MAb, par le biais des processus de sémantisation et d’intégration des souvenirs qui permettent de former des représentations abstraites à partir des expériences vécues. Par ailleurs, nous avons également montré que le sens subjectif de soi est inhérent à toutes les autres composantes du Self. Par l’étude d’un cas unique et d’imagerie volumétrique de groupe, le cortex préfrontal médian a été mis en évidence comme substrat commun à toutes les composantes du Self, suggérant un rôle clé de cette structure pour supporter le sens subjectif de soi. Ces résultats ouvrent des pistes de remédiation par la réminiscence basée sur les mécanismes de sémantisation, d’intégration et sur les aspects émotionnels, au centre desquels se trouvent les souvenirs définissant-le-soi. Aussi notre étude engage-t-elle à analyser ces composantes du Self au sein de réseaux, en connectivité fonctionnelle et anatomique.The present study aimed at studying autobiographical memory (AbM) in patients at early stages of Alzheimer’s disease, as well as at analyzing the link between AbM and the Self components (as defined by Prebble et al., 2013), and finally, at investigating its neuro-anatomical correlates. The results we obtained confirmed AbM is damaged in patients with regards to episodic and emotional components, whatever the age of the memory. The deficit in episodic memory was associated with medial temporal lobe atrophy, with the left hippocampus seemingly involved in the temporal context of the memories and the right amygdala in the emotional component. Conversely, specificity of remaining emotional memories was relatively preserved, as well as semanticized memories, which rely on the temporal neocortex. In the context of the Self more generally, our results highlight a relationship between the conceptual-Self and autobiographical memories, through semanticization and integration processes, which allow the formation of the most abstracted forms of self-representations. Moreover, the subjective sense of Self appears as a prerequisite to all other Self components. Based upon a case study and a volumetric group study, we were able to show that the implication of the medial prefrontal cortex is common to all Self components, suggesting its key role for the subjective sense of Self. Our results point to a potential rehabilitation therapy based on reinforcing self-defining memories to strengthen the Self. This work will be completed by the study of functional and anatomical networks sustaining the Self

CASPR2 antibody encephalitis presenting as transient epileptic amnesia

International audienceNo abstract availabl