Personality, Alzheimer's disease and behavioural and cognitive symptoms of dementia: the PACO prospective cohort study protocol

International audienceBACKGROUND: Alzheimer's disease is characterised by a loss of cognitive function and behavioural problems as set out in the term "Behavioural and Psychological Symptoms of Dementia". These behavioural symptoms have heavy consequences for the patients and their families. A greater understanding of behavioural symptoms risk factors would allow better detection of those patients, a better understanding of crisis situations and better management of these patients. Some retrospective studies or simple observations suggested that personality could play a role in the occurrence of behavioural symptoms. Finally, performance in social cognition like facial recognition and perspective taking could be linked to certain personality traits and the subsequent risks of behavioural symptoms. We propose to clarify this through a prospective, multicentre, multidisciplinary study. Main Objective: -To assess the effect of personality and life events on the risk of developing behavioural symptoms. Secondary Objectives: -To evaluate, at the time of inclusion, the connection between personality and performance in social cognition tests; -To evaluate the correlation between performance in social cognition at inclusion and the risks of occurrence of behavioural symptoms; -To evaluate the correlation between regional cerebral atrophy, using brain Magnetic Resonance Imaging at baseline, and the risk of behavioural symptoms.METHODS/DESIGN: Study type and Population: Prospective multicentre cohort study with 252 patients with Alzheimer's disease at prodromal or mild dementia stage. The inclusion period will be of 18 months and the patients will be followed during 18 months. The initial evaluation will include: a clinical and neuropsychological examination, collection of behavioural symptoms data (Neuropsychiatric-Inventory scale) and their risk factors, a personality study using both a dimensional (personality traits) and categorical approach, an inventory of life events, social cognition tests and an Magnetic Resonance Imaging. Patients will be followed every 6 months (clinical examination and collection of behavioural symptoms data and risk factors) during 18 months.DISCUSSION: This study aims at better identifying the patients with Alzheimer's disease at high risk of developing behavioural symptoms, to anticipate, detect and quickly treat these disorders and so, prevent serious consequences for the patient and his caregivers.TRIAL REGISTRATION: ClincalTrials.gov: NCT01297140

Advances and Insights into Neurological Practice 2016-17

Papers published by the European Journal of Neurology reflect the broad interest of practicing neurologists in advances in the aetiology, diagnosis and management of neurological disorders. As a general journal, the proportion of papers in the different subject areas reasonably reflects the case load of a practising neurologist. Stroke represents the largest proportion of papers published, including those on pathophysiology (1-23), acute stroke management (24-47) and the outcome of patients who have suffered stroke (48-72). This article is protected by copyright. All rights reserved

Neural correlates of neuropsychiatric symptoms in Alzheimer’s disease

La maladie d’Alzheimer (MA) est la plus répandue des maladies neurodégénératives. Elle se caractérise par une déficience cognitive puis fonctionnelle souvent associée à des Symptômes Psychologiques et Comportementaux des Démences (SPCD). Les études longitudinales de corrélations physiopathologiques des SPCD sont rares et difficiles à évaluer en raison de grandes hétérogénéités dans les populations étudiées. Associée à l’expertise clinique, la neuroimagerie fournit des indices cruciaux pour comprendre les corrélats neuroanatomiques des SPCD les plus invalidants dans la MA. Dans les travaux de recherche, il apparaît déterminant de considérer la MA associée à certaines co-pathologies neurodégénératives et vasculaires. En effet, alors que les patients jeunes sont les plus touchés par des lésions pures, le vieillissement favorise l'apparition de co-lésions liées à la MA et aux Maladies à Corps de Lewy (MCL) et Maladies CérébroVasculaires (MCV).Soutenu par un travail bibliographique sur la MA et ses co-lésions, ce travail de thèse s’appuie sur 3 études complémentaires. La 1ière porte sur une revue de littérature ayant pour objectif d’évaluer les corrélats neuroradiologiques des SPCD dans la MA. Différents moteurs de recherche de données bibliographiques ont permis d’identifier 118 études évaluant cet objectif. Un modèle global des corrélats cérébraux des SPCD a été proposé pour soutenir la forte implication de la région frontale. Aussi, des stratégies méthodologiques ont été suggérées pour aider à diriger de futures recherches. La 2ième étude avait pour objectif d’évaluer si le profil d’atrophie cérébrale pouvait déterminer le risque de développer des SPCD dans la MA. Une analyse volumétrique de données IRM a été effectuée pour évaluer l’atrophie régionale en incluant 53 patients MA sans SPCD significatifs à l’inclusion et 40 contrôles. Vingt-quatre structures dans les régions frontale, temporale, pariétale, occipitale et sous-corticale ainsi que dans le cervelet ont été identifiées comme associées aux SPCD. L'atrophie frontale semble être le prédicteur le plus significatif des SPCD. La 3ième étude s’inscrit en continuité et en perspective de ce travail de thèse. Elle a pour but d’explorer ces questions chez des patients atteints de MA associée à des co-lésions de MCL et MCVAlzheimer's disease (AD) is the most common neurodegenerative disease. AD is characterized by cognitive and functional impairment often associated with Behavioural and Psychological Symptoms of Dementia (BPSD). Longitudinal studies of pathophysiological correlations of BPSD are rare and difficult to evaluate due to large heterogeneities in the populations studied. Associated with clinical expertise, neuroimaging provides crucial clues to understand the neuroanatomic correlates of the most disabling BPSD in AD. It seems important to consider in the research, AD with some neurodegenerative and vascular co-pathologies. Indeed, while young patients are the most affected by pure lesions, aging favors the appearance of co-lesions related to AD and Lewy body disease and cerebrovascular diseases.Supported by a bibliographic work on AD and its co-lesions, this work is based on 3 complementary studies. The first concerns a literature review aimed at evaluating neuroradiological correlates of BPSD in AD. Bibliographic search has led to 118 studies evaluating this objective. A global pattern of cerebral cortical brain regions has been proposed to support the strong involvement of the frontal region. Also, methodological strategies have been suggested to help direct future research. The aim of the second study was to evaluate whether the profile of cerebral atrophy could determine the risk of developing BPSD in AD. A volumetric analysis of MRI data was performed to evaluate regional atrophy by including 53 patients with no significant BPSD at baseline and 40 controls. Twenty-four structures in the frontal, temporal, parietal, occipital and subcortical regions as well as in the cerebellum were identified as associated with BPSD. Frontal atrophy appears to be the most significant predictor of BPSD. The third study is in continuity of this work of thesis. It is intended to explore these issues in patients with AD associated with co-lesion

Corrélats neuroradiologiques des troubles du comportement dans la Maladie d’Alzheimer

Alzheimer's disease (AD) is the most common neurodegenerative disease. AD is characterized by cognitive and functional impairment often associated with Behavioural and Psychological Symptoms of Dementia (BPSD). Longitudinal studies of pathophysiological correlations of BPSD are rare and difficult to evaluate due to large heterogeneities in the populations studied. Associated with clinical expertise, neuroimaging provides crucial clues to understand the neuroanatomic correlates of the most disabling BPSD in AD. It seems important to consider in the research, AD with some neurodegenerative and vascular co-pathologies. Indeed, while young patients are the most affected by pure lesions, aging favors the appearance of co-lesions related to AD and Lewy body disease and cerebrovascular diseases.Supported by a bibliographic work on AD and its co-lesions, this work is based on 3 complementary studies. The first concerns a literature review aimed at evaluating neuroradiological correlates of BPSD in AD. Bibliographic search has led to 118 studies evaluating this objective. A global pattern of cerebral cortical brain regions has been proposed to support the strong involvement of the frontal region. Also, methodological strategies have been suggested to help direct future research. The aim of the second study was to evaluate whether the profile of cerebral atrophy could determine the risk of developing BPSD in AD. A volumetric analysis of MRI data was performed to evaluate regional atrophy by including 53 patients with no significant BPSD at baseline and 40 controls. Twenty-four structures in the frontal, temporal, parietal, occipital and subcortical regions as well as in the cerebellum were identified as associated with BPSD. Frontal atrophy appears to be the most significant predictor of BPSD. The third study is in continuity of this work of thesis. It is intended to explore these issues in patients with AD associated with co-lesionsLa maladie d’Alzheimer (MA) est la plus répandue des maladies neurodégénératives. Elle se caractérise par une déficience cognitive puis fonctionnelle souvent associée à des Symptômes Psychologiques et Comportementaux des Démences (SPCD). Les études longitudinales de corrélations physiopathologiques des SPCD sont rares et difficiles à évaluer en raison de grandes hétérogénéités dans les populations étudiées. Associée à l’expertise clinique, la neuroimagerie fournit des indices cruciaux pour comprendre les corrélats neuroanatomiques des SPCD les plus invalidants dans la MA. Dans les travaux de recherche, il apparaît déterminant de considérer la MA associée à certaines co-pathologies neurodégénératives et vasculaires. En effet, alors que les patients jeunes sont les plus touchés par des lésions pures, le vieillissement favorise l'apparition de co-lésions liées à la MA et aux Maladies à Corps de Lewy (MCL) et Maladies CérébroVasculaires (MCV).Soutenu par un travail bibliographique sur la MA et ses co-lésions, ce travail de thèse s’appuie sur 3 études complémentaires. La 1ière porte sur une revue de littérature ayant pour objectif d’évaluer les corrélats neuroradiologiques des SPCD dans la MA. Différents moteurs de recherche de données bibliographiques ont permis d’identifier 118 études évaluant cet objectif. Un modèle global des corrélats cérébraux des SPCD a été proposé pour soutenir la forte implication de la région frontale. Aussi, des stratégies méthodologiques ont été suggérées pour aider à diriger de futures recherches. La 2ième étude avait pour objectif d’évaluer si le profil d’atrophie cérébrale pouvait déterminer le risque de développer des SPCD dans la MA. Une analyse volumétrique de données IRM a été effectuée pour évaluer l’atrophie régionale en incluant 53 patients MA sans SPCD significatifs à l’inclusion et 40 contrôles. Vingt-quatre structures dans les régions frontale, temporale, pariétale, occipitale et sous-corticale ainsi que dans le cervelet ont été identifiées comme associées aux SPCD. L'atrophie frontale semble être le prédicteur le plus significatif des SPCD. La 3ième étude s’inscrit en continuité et en perspective de ce travail de thèse. Elle a pour but d’explorer ces questions chez des patients atteints de MA associée à des co-lésions de MCL et MC

Contrast-enhanced ultrasound: a new method for TIPS follow-up

International audienc

Neuroanatomical Correlates of Recognizing Face Expressions in Mild Stages of Alzheimer's Disease

Early Alzheimer's disease can involve social disinvestment, possibly as a consequence of impairment of nonverbal communication skills. This study explores whether patients with Alzheimer's disease at the mild cognitive impairment or mild dementia stage have impaired recognition of emotions in facial expressions, and describes neuroanatomical correlates of emotion processing impairment. As part of the ongoing PACO study (personality, Alzheimer's disease and behaviour), 39 patients with Alzheimer's disease at the mild cognitive impairment or mild dementia stage and 39 matched controls completed tests involving discrimination of four basic emotions-happiness, fear, anger, and disgust-on photographs of faces. In patients, automatic volumetry of 83 brain regions was performed on structural magnetic resonance images using MAPER (multi-atlas propagation with enhanced registration). From the literature, we identified for each of the four basic emotions one brain region thought to be primarily associated with the function of recognizing that emotion. We hypothesized that the volume of each of these regions would be correlated with subjects' performance in recognizing the associated emotion. Patients showed deficits of basic emotion recognition, and these impairments were correlated with the volumes of the expected regions of interest. Unexpectedly, most of these correlations were negative: better emotional facial recognition was associated with lower brain volume. In particular, recognition of fear was negatively correlated with the volume of amygdala, disgust with pallidum, and happiness with fusiform gyrus. Recognition impairment in mild stages of Alzheimer's disease for a given emotion was thus associated with less visible atrophy of functionally responsible brain structures within the patient group. Possible explanations for this counterintuitive result include neuroinflammation, regional β-amyloid deposition, or transient overcompensation during early stages of Alzheimer's disease

Contrast-enhanced ultrasound: a new method for TIPS follow-up

International audienc

Proposition of a multiparametric model-based method for breast lesion differentiation: a feasibility study

International audienceElastography has been introduced to complement mammography and sonography with the purpose of better differentiating benign from malignant lesions. With this regard, criteria such as elasticity score and strain index, also termed strain ratio (SR), have been introduced. SR was defined as the mean strain value of the background divided by the mean strain value within the lesion

Neuroticism-Withdrawal and Neuroticism-Volatility Differently Influence the Risk of Neuropsychiatric Symptoms in Alzheimer's Disease.

Neuroticism is recognized as the personality domain that is most strongly associated with behavioral and psychological symptoms (BPS) of Alzheimer's disease (AD). Two sub-components of neuroticism have been recently isolated. Neuroticism-withdrawal (N-withdrawal) refers to the tendency to internalize negative emotion, whereas neuroticism-volatility (N-volatility) reflect the predisposition to externalize negative emotions. The objective of the current study was to investigate the specific influence of these two sub-components of neuroticism on BPS. One hundred eighty-seven patients with prodromal or mild AD were drawn from the PACO study (Personalité Alzheimer COmportement). Neuroticism and its facets were assessed at baseline using the NEO-PI-R inventory. N-withdrawal and N-volatility were isolated using a principal component analysis led on the six facets composing neuroticism. BPS were measured with the short version of Neuropsychiatric Inventory (NPI-Q) and collected at baseline, then every 6 months over an 18-month follow-up. Linear mixed-effect analyses were conducted to investigate the association between N-withdrawal, N-volatility, and the severity of BPS over the follow-up. Mean age of the participant was 79.2±6.5; 59% were female; mean MMSE was 24.5±2.5. Both N-volatility and N-withdrawal were related with the NPI-Q (p < 0.001; p = 0,004). N-withdrawal was positively associated with anxiety (p = 0.001) and depression (p = 0.002), while N-volatility was positively related to delusions (p = 0.004), agitation/aggression (p < 0.001), irritability/volatility (p = 0.037), and apathy (p = 0.021). The present study demonstrates that N-volatility and N-withdrawal influence the risk of developing BPS in a different way. These results highlight the relevance of considering sub-components of neuroticism when studying links between personality and BPS

In Vivo Response to Compression of 35 Breast Lesions Observed with a Two-Dimensional Locally Regularized Strain Estimation Method

International audienceThe objective of this study was to assess the in vivo performance of our 2-D locally regularized strain estimation method with 35 breast lesions, mainly cysts, fibroadenomas and carcinomas. The specific 2-D deformation model used, as well as the method's adaptability, led to an algorithm that is able to track tissue motion from radiofrequency ultrasound images acquired in clinical conditions. Particular attention was paid to strain estimation reliability, implying analysis of the mean normalized correlation coefficient maps. For all lesions examined, the results indicated that strain image interpretation, as well as its comparison with B-mode data, should take into account the information provided by the mean normalized correlation coefficient map. Different trends were observed in the tissue response to compression. In particular, carcinomas appeared larger in strain images than in B-mode images, resulting in a mean strain/B-mode lesion area ratio of 2.59 ± 1.36. In comparison, the same ratio was assessed as 1.04 ± 0.26 for fibroadenomas. These results are in agreement with those of previous studies, and confirm the interest of a more thorough consideration of size difference as one parameter discriminating between malignant and benign lesions