Cognitive decline in Huntington's disease in the Digitalized Arithmetic Task (DAT)

Background Efficient cognitive tasks sensitive to longitudinal deterioration in small cohorts of Huntington’s disease (HD) patients are lacking in HD research. We thus developed and assessed the digitized arithmetic task (DAT), which combines inner language and executive functions in approximately 4 minutes. Methods We assessed the psychometric properties of DAT in three languages, across four European sites, in 77 early-stage HD patients (age: 52 ± 11 years; 27 females), and 57 controls (age: 50 ± 10, 31 females). Forty-eight HD patients and 34 controls were followed up to one year with 96 participants who underwent MRI brain imaging (HD patients = 46) at baseline and 50 participants (HD patients = 22) at one year. Linear mixed models and Pearson correlations were used to assess associations with clinical assessment. Results At baseline, HD patients were less accurate (p = 0.0002) with increased response time (p<0.0001) when compared to DAT in controls. Test-retest reliability in HD patients ranged from good to excellent for response time (range: 0.63–0.79) and from questionable to acceptable for accuracy (range: r = 0.52–0.69). Only DAT, the Mattis Dementia Rating Scale, the Symbol Digit Modalities Test, and Total Functional Capacity scores were able to detect a decline within a one-year follow-up in HD patients (all p< 0.05). In contrast with all the other cognitive tasks, DAT correlated with striatal atrophy over time (p = 0.037) but not with motor impairment. Conclusions DAT is fast, reliable, motor-free, applicable in several languages, and able to unmask cognitive decline correlated with striatal atrophy in small cohorts of HD patients. This likely makes it a useful endpoint in future trials for HD and other neurodegenerative diseases

A new approach to digitized cognitive monitoring: validity of the SelfCog in Huntington's disease

Cognitive deficits represent a hallmark of neurodegenerative diseases, but evaluating their progression is complex. Most current evaluations involve lengthy paper-and-pencil tasks which are subject to learning effects dependent on the mode of response (motor or verbal), the countries’ language or the examiners. To address these limitations, we hypothesized that applying neuroscience principles may offer a fruitful alternative. We thus developed the SelfCog, a digitized battery that tests motor, executive, visuospatial, language and memory functions in 15 min. All cognitive functions are tested according to the same paradigm, and a randomization algorithm provides a new test at each assessment with a constant level of difficulty. Here, we assessed its validity, reliability and sensitivity to detect decline in early-stage Huntington’s disease in a prospective and international multilingual study (France, the UK and Germany). Fifty-one out of 85 participants with Huntington’s disease and 40 of 52 healthy controls included at baseline were followed up for 1 year. Assessments included a comprehensive clinical assessment battery including currently standard cognitive assessments alongside the SelfCog. We estimated associations between each of the clinical assessments and SelfCog using Spearman’s correlation and proneness to retest effects and sensitivity to decline through linear mixed models. Longitudinal effect sizes were estimated for each cognitive score. Voxel-based morphometry and tract-based spatial statistics analyses were conducted to assess the consistency between performance on the SelfCog and MRI 3D-T1 and diffusion-weighted imaging in a subgroup that underwent MRI at baseline and after 12 months. The SelfCog detected the decline of patients with Huntington’s disease in a 1-year follow-up period with satisfactory psychometric properties. Huntington’s disease patients are correctly differentiated from controls. The SelfCog showed larger effect sizes than the classical cognitive assessments. Its scores were associated with grey and white matter damage at baseline and over 1 year. Given its good performance in longitudinal analyses of the Huntington’s disease cohort, it should likely become a very useful tool for measuring cognition in Huntington’s disease in the future. It highlights the value of moving the field along the neuroscience principles and eventually applying them to the evaluation of all neurodegenerative diseases

Cognition et Interactions Sociales dans la Maladie d'Alzheimer : Contributions cliniques à l'étude des processus d'adaptation à autrui chez les patients atteints de la Maladie d'Alzheimer

Impairments of social interactions have been described in patients with Alzheimer's disease (AD) in order to explain some of their behavioural difficulties, such as the lack of awareness of their own memory impairments (metamemory), or difficulties to infer the mental states of others (Theory of Mind, ToM). By adopting, firstly, a cognitive approach, then a sociological perspective to social adaptation and to the role of others in regulating our behaviour, we firstly proposed to AD patients and matched controls a comprehensive assessment protocol for different aspects of frontal functioning: Self-awareness (metamemory), awareness of the others (ToM) and executive cognitive functioning. In the second part on this thesis, AD patients, patients with mild cognitive impairments and normal controls were given dynamic tasks assessing social interactions with the examiner and perspective-taking skills. This thesis leads to the following conclusions (1) metamemory and ToM abilities in AD should be fractionated; (2) executive cognitive deficits are unable to explain the performance of patients; and (3) using alternative interpretations borrowed from the realms of social psychology and sociology is important to the understanding of the social interaction impairments of AD patients, in terms of difficulties in perspective taking and in maintenance of a singular social role.Des perturbations des interactions sociales sont décrites chez les patients atteints de la Maladie d'Alzheimer (MA), afin d'expliquer certaines difficultés psycho-comportementales caractéristiques de cette pathologie, comme l'absence de conscience des troubles mnésiques (métamémoire) ou des difficultés d'inférences d'états mentaux à autrui (Théorie de l'Esprit, TdE). En adoptant, dans un premier temps, une conception cognitive puis une approche sociologique de l'adaptation sociale et du rôle d'autrui dans la régulation des comportements, nous avons proposé à des patients atteints de MA et des contrôles appariés un protocole d'évaluation de différents aspects du fonctionnement frontal : la conscience de soi (métamémoire), la conscience de l'autre (TdE) et le fonctionnement exécutif cognitif. Dans une deuxième partie, des participants avec une MA, des patients avec des déficits cognitifs légers et des contrôles appariés ont été soumis à des tâches dynamiques évaluant l'interaction sociale avec l'examinateur et les capacités de prise de perspectives. La présente thèse permet de conclure à (1) un fractionnement des capacités de métamémoire et de TdE ; (2) une insuffisance des variables exécutives cognitives pour expliquer les performances des patients aux tâches de TdE et de métamémoire ; (3) l'importance de recourir à des interprétations alternatives empruntées aux domaines de la psychologie sociale et de la sociologie pour comprendre les difficultés d'interaction sociale des patients MA sous l'angle de la problématique de prise de perspective et de maintien d'un rôle social singulier

Cognition et interactions sociales dans la maladie d'Alzheimer (contributions cliniques à l'étude des processus d'adaptation à autrui chez les patients atteints de la maladie d'Alzheimer)

Des perturbations des interactions sociales sont décrites chez les patients atteints de la Maladie d'Alzheimer (MA), afin d'expliquer certaines difficultés psycho-comportementales caractéristiques de cette pathologie, comme l'absence de conscience des troubles mnésiques (métamémoire) ou des difficultés d'inférences d'états mentaux à autrui (Théorie de l'Esprit, TdE). En adoptant, dans un premier temps, une conception cognitive puis une approche sociologique de l'adaptation sociale et du rôle d'autrui dans la régulation des comportements, nous avons proposé à des patients atteints de MA et des contrôles appariés un protocole d'évaluation de différents aspects du fonctionnement frontal : la conscience de soi (métamémoire), la conscience de l'autre (TdE) et le fonctionnement exécutif cognitif. Dans une deuxième partie, des participants avec une MA, des patients avec des déficits cognitifs légers et des contrôles appariés ont été soumis à des tâches dynamiques évaluant l'interaction sociale avec l'examinateur et les capacités de prise de perspectives. La présente thèse permet de conclure à (1) un fractionnement des capacités de métamémoire et de TdE ; (2) une insuffisance des variables exécutives cognitives pour expliquer les performances des patients aux tâches de TdE et de métamémoire ; (3) l'importance de recourir à des interprétations alternatives empruntées aux domaines de la psychologie sociale et de la sociologie pour comprendre les difficultés d'interaction sociale des patients MA sous l'angle de la problématique de prise de perspective et de maintien d'un rôle social singulier.Impairments of social interactions have been described in patients with Alzheimer's disease (AD) in order to explain some of their behavioural difficulties, such as the lack of awareness of their own memory impairments (metamemory), or difficulties to infer the mental states of others (Theory of Mind, ToM). By adopting, firstly, a cognitive approach, then a sociological perspective to social adaptation and to the role of others in regulating our behaviour, we firstly proposed to AD patients and matched controls a comprehensive assessment protocol for different aspects of frontal functioning: Self-awareness (metamemory), awareness of the others (ToM) and executive cognitive functioning. In the second part on this thesis, AD patients, patients with mild cognitive impairments and normal controls were given dynamic tasks assessing social interactions with the examiner and perspective-taking skills. This thesis leads to the following conclusions (1) metamemory and ToM abilities in AD should be fractionated; (2) executive cognitive deficits are unable to explain the performance of patients; and (3) using alternative interpretations borrowed from the realms of social psychology and sociology is important to the understanding of the social interaction impairments of AD patients, in terms of difficulties in perspective taking and in maintenance of a singular social role.ANGERS-BU Lettres et Sciences (490072106) / SudocSudocFranceF

Theory of Mind and social reserve: Alternative hypothesis of progressive Theory of Mind decay during different stages of Alzheimer’s disease

International audienceAlthough Theory of Mind (ToM) is thought to be impaired in Alzheimer’s disease (AD), it remains unclear whether this impairment is linked to the level of task complexity, the heterogeneity of the studied patients, or the implication of executive dysfunctions. To elucidate this point, 42 AD patients, divided into two subgroups [moderate AD (mAD) patients (n&nbsp;=&nbsp;19) and early AD (eAD) patients (n&nbsp;=&nbsp;23)], and 23 matched healthy older subjects (HO) were enrolled. All participants were given (1) a false-belief task (cognitive ToM), (2) a revised version of the “Reading the Mind in the Eyes” test (affective ToM), and (3) a composite task designed to assess ToM abilities with minimal cognitive demands. Participants were also given executive tasks assessing inhibition, shifting, and updating processes. We observed a significant impairment of cognitive and composite ToM abilities in eAD patients compared with mAD patients. There was no impairment of affective ToM. Stepwise regression revealed that measures of global efficiency and executive functions (EFs) were the best predictors of progressive decay of ToM scores. These results indicate that cognitive aspects of ToM are more sensitive to AD progression than affective tasks. They also show that ToM abilities are more affected by dementia severity than by task complexity. One explanation of our results is the presence of compensatory mechanisms (social reserve) in AD

Comprehensive assessment of executive functioning following childhood severe traumatic brain injury: clinical utility of the child executive functions battery

International audienceObjectives To perform a detailed description of executive functioning following moderate-to-severe childhood traumatic brain injury (TBI), and to study demographic and severity factors influencing outcome.Methods A convenience sample of children/adolescents aged 7–16 years, referred to a rehabilitation department after a TBI ( n = 43), was compared to normative data using a newly developed neuropsychological test battery (Child Executive Functions Battery—CEF-B) and the BRIEF. Results Performance in the TBI group was significantly impaired in most of the CEF-B subtests, with moderate to large effect sizes. Regarding everyday life, patients were significantly impaired in most BRIEF clinical scales, either in parent or in teacher reports. Univariate correlations in the TBI group did not yield significant correlations between the CEF-B and socio-economic status, TBI severity, age at injury, or time since injury.Conclusion Executive functioning is severely altered following moderate-to-severe childhood TBI and is best assessed using a combination of developmentally appropriate neuropsychological tests and behavioral ratings to provide a comprehensive understanding of children’s executive functions