D. Le Gall

Cognitive changes in asymptomatic carriers of the Huntington disease mutation gene

Huntington disease (HD) is a neurodegenerative disorder due to an excessive number of CAG repeats in the IT15 gene on chromosome 4. Studies of cognitive function in asymptomatic gene carriers have yielded contradictory results. This study compared cognitive performance in 44 subjects with the HD mutation (group of carriers) who had no clinical signs of HD and 39 at‐risk individuals without HD mutation (group of non‐carriers). Neuropsychological evaluation focused on global cognitive efficiency, psychomotor speed, attentional, executive and memory functions. Significant differences, with lower performances in the group of gene carriers, were detected for some measures of psychomotor speed, attention and executive functioning (all P < 0.01). More differences between groups were observed for memory measures, in particular on the California Verbal Memory Test. Complementing these observations, cognitive scores were correlated with age in the group of gene carriers, but not in the group of non‐carriers. This suggests that the cognitive changes precede the appearance of the motor and psychiatric symptoms in HD and that tests proved to be sensitive to early HD deficiencies are better suited than global cognitive efficiency scales to observe them.

Deficit of cognitive inhibition in depressed elderly: a neurocognitive marker of suicidal risk.

BACKGROUND Cognitive deficits, in relation to ventral and dorsal prefrontal cortex dysfunctions, have been associated with a higher risk of suicidal acts in young adult patients. Although a public health concern, much less is known about the neurocognitive basis of suicidal behavior in elderly. Here, we aimed at assessing alterations in cognitive inhibition, a suspected major mechanism of the suicidal vulnerability, in suicidal depressed elderly. METHODS We compared 20 currently depressed patients, aged 65 and older who recently attempted suicide to 20 elderly subjects with a current depression but no personal history of suicide attempt and 20 elderly controls. Using an extensive neuropsychological battery, we particularly examined different aspects of cognitive inhibition: access to relevant information (using the Reading with distraction task), suppression of no longer relevant information (Trail Making Test, Rule Shift Cards), and restraint of cognitive resources to relevant information (Stroop test, Hayling Sentence Completion test, Go/No-Go). RESULTS After adjustment for age, intensity of depression, Mini-Mental State Examination score and speed of information processing, suicidal depressed elderly showed significant impairments in all 3 domains of cognitive inhibition in comparison to both control groups. LIMITATIONS Our results need replication in a larger sample size. CONCLUSIONS Our study suggests that the inability to inhibit neutral information access to working memory, restrain and delete irrelevant information may impair the patients capacity to respond adequately to stressful situations subsequently leading to an increased risk of suicidal behavior during late-life depression. Interventions may be developed to specifically target cognitive impairment in the prevention of suicide in depressed elderly.

Étude de la planification de l’action au moyen du test du plan du zoo dans la maladie d’Alzheimer

Resume Introduction Une degradation des fonctions executives est regulierement rapportee dans la maladie d’Alzheimer, mais les capacites de planification de l’action paraissent assez peu etudiees dans le cadre de cette pathologie neurodegenerative. Objectif L’objectif de cette etude etait donc d’examiner les deux principales composantes de la planification (la formulation et l’execution d’un plan) dans la maladie d’Alzheimer a partir d’une epreuve simulant l’execution d’une activite realiste empruntee a la batterie d’evaluation comportementale du syndrome dysexecutif. Cette epreuve presente le plan d’un zoo dont le sujet doit effectuer la visite dans deux conditions : une condition formulation ou il doit organiser lui-meme ses deplacements en respectant la liste des endroits a visiter et des regles precises, et une condition execution ou il doit suivre l’itineraire de visite indique. L’epreuve a ete proposee a 18 patients Alzheimer et 15 controles âges sains apparies. Resultats Les analyses de variance ont principalement montre que les patients avec maladie d’Alzheimer etaient significativement moins performants que les controles pour l’ensemble des parametres d’appreciation de la performance (temps, score de sequence, erreurs), ce dans les deux conditions de realisation. L’ecart entre les deux conditions de realisation etait plus important pour les patients Alzheimer. Les difficultes de planification correlaient principalement avec les modifications comportementales (en particulier motivationnelles) constatees par les proches des patients au quotidien. Conclusion Ce travail confirme que la maladie d’Alzheimer s’accompagne d’une diminution des capacites de planification de l’action qui parait liee a la fois a une difficulte a formuler des plans et a les executer et dont l’origine semble en partie liee a des modifications du comportement.

Assessment of everyday executive functioning in children with frontal or temporal epilepsies

Executive functions are particularly vulnerable in case of brain disruption during childhood, when the brain is not fully mature. Some studies showed impairments of executive functions in children with epilepsy, but only a few of them investigated the impact of executive dysfunctions on daily life. The aim of this study was to understand the everyday executive functioning of children with epilepsy both at home and in school. We administered the Behavior Rating Inventory of Executive Function to parents and teachers of 53 children (7-16 years of age) with structural epilepsies or epilepsies of unknown cause of temporal lobe (n=25) or frontal lobe (n=28). The results indicated a global executive impairment in the whole group of patients, compared with normative data, with no difference between the group with temporal lobe epilepsy (TLE) and that with frontal lobe epilepsy (FLE), except for monitor domain, which seemed more frequently impaired in the group with FLE. Congruence between parent and teacher ratings was found. The frequency of seizures was not related to executive dysfunction, whereas the number of antiepileptic drugs tended to positively correlate with working memory impairment. Onset of epilepsy at a younger age was also related to more executive difficulties but only according to teacher ratings. Lastly, duration of epilepsy was strongly associated with executive deficits reported in the context of school. Our results support the executive dysfunction hypothesis in daily life of children with structural focal epilepsy or focal epilepsy of unknown cause and are consistent with the early brain vulnerability hypothesis currently prevalent in the context of child neuropsychology. The BRIEF appears to be a clinically useful tool for assessing executive function impairment in this clinical population.

Lobe frontal, fonctions exécutives et controle cognitif

Resume Il y a 30 ans se mettait en place le socle qui preside aux approches actuelles des fonctions executives. L’interpretation des troubles comportementaux et cognitifs lies a la pathologie frontale a conduit a individualiser l’atteinte preferentielle des fonctions de controle ou executives, intervenant principalement dans les situations necessitant une articulation des actions ou pensees dirigees vers un but finalise. L’intervention privilegiee de la memoire de travail, initialement evoquee sur la base de travaux experimentaux chez le singe, a egalement fortement influence les approches conceptuelles dominees par les modeles de Shallice et de Baddeley. Depuis cette epoque, de nombreux travaux bases sur la pathologie et l’imagerie fonctionnelle ont permis de proposer une specification des operations de controle intervenant tant dans les tests les plus abstraits que sur la regulation des comportements. En outre ils remettent en question une architecture fonctionnelle reposant sur un systeme de controle unique. Au plan pratique ces travaux ont conduit a proposer des criteres diagnostiques de syndrome dysexecutif et une strategie d’exploration basee sur une batterie de tests et un heteroquestionnaire comportemental dont la passation conjointe doit etre au mieux systematisee.The approach of executive functions began with the early description of behavioural disorders induced by frontal damage. The development of neuropsychology has led to the description of a large variety of cognitive disorders. The interpretation in cognitive terms of these disorders has emphasized the critical impairment of executive functions which are involved in non-routine situations. The role of working memory, initially suggested by animal studies, has also largely influenced theoretical approaches. Numerous studies have been interpreted within the theoretical frameworks developed by Shallice and by Baddeley. A large amount of studies have allowed the specification of control processes (initiation, inhibition...). Recent studies are beginning to investigate cognitive disorders underlying behavioural changes such as deficits of emotional, social and metacognitive processes. In addition these studies seriously question the assumption of a unique central control system. These studies have deeply influenced the clinical approach, the assessment and the diagnosis of executive syndrome. For clinical practice, these data lead to favour specific assessment of some key behavioural and cognitive deficits based on a battery of tests and structured interview of an informant.

Discrepancy between social and nonsocial decision-making under uncertainty following prefrontal lobe damage: the impact of an interactionist approach.

ABSTRACT Deficits in decision-making are thought to contribute significantly to socio-behavioral impairments of patients with frontal lobe damage. The purpose of this study was to test the hypothesis of whether the inappropriate social behavior of patients with frontal lesions can be viewed as the product of a general failure of decision-making ability or as the result of socio-cognitive impairment. We studied a group of patients with prefrontal lesions (FL patients, n = 15) and a group of matched healthy controls (n = 30) on the Iowa Gambling task (IGT) of nonsocial decision-making, environmental dependency phenomena (EDP) during social interaction, and the “reading the mind in the eyes” and “character intention task” of theory of mind (TOM) tasks. The FL patients were impaired in both TOM and EDP protocols but, surprisingly, they behaved appropriately in the IGT. In addition, FL patients with EDP did not differ in executive functioning, IGT and TOM measures from those who did not demonstrate these behavioral disorders. The right orbitofrontal cortex was associated with social decision-making deficits. By adopting an interactionist approach, this study raises the possibility of identifying components of social and nonsocial decision-making, which could be helpful in understanding the behavioral disorders of FL patients.

Cognitive inhibition and quality of life in schizophrenia: A pilot study

AIM To compare cognitive inhibition and quality of life in patients with schizophrenia and healthy controls. METHODS Ten patients with schizophrenia were compared to 10 healthy controls, matched for age, sex, and educational level. Cognitive inhibition was examined by: 1) access to relevant information (Reading with distraction task), 2) suppression of no longer relevant information (Trail Making Test), and 3) restraint of cognitive resources to relevant information (Stroop Test, Hayling Sentence Completion Test, Go/No-Go Test). Montgomery Asberg Depression Rating Scale, Positive and Negative Syndrome Scale, and Schizophrenia-Quality of Life scale (S-QoL) were also used. RESULTS Patients with schizophrenia showed a significant impairment in the suppression function of cognitive inhibition only, in comparison to the control group. Their access and restraint functions of cognitive inhibition were preserved. No relationship between quality of life and cognitive inhibition was found in patients with schizophrenia. CONCLUSIONS During the stabilization phase of schizophrenia, the ability to inhibit neutral information access to working memory, and to restrain and suppress irrelevant information may not impair the patients capacity to respond adequately to stressful situations, and thus would do not impact their quality of life.

Fish consumption and dementia: keep the vitamin D in memory

Sir, Recently, Morris [1] reported the results of an interesting literature review on the association between nutrition and Alzheimer disease (AD), focusing particularly on dietary fats. The author collected epidemiological data, mostly from Northern Europe, showing an inverse relationship between fish consumption and dementia. Morris attributed this effect to the omega-3 polyunsaturated fatty acids (n-3PUFA) which are involved in the neuronal membrane and in the maintenance of brain function [1]. However, the author stressed that, despite the well-demonstrated decreased AD risk in populations with elevated intakes of fish and n-3PUFA, baseline plasma n-3PUFA concentrations could not predict dementia in the Canadian Study of Health and Aging [1,2]. Furthermore, clinical trials failed to show any protective effect of n-3PUFA supplementation on cognitive decline in advanced-stage AD [1,2]. The main explanations for these mixed results could be that either the intake of n-3PUFA is efficient only in primary prevention at the mild cognitive impairment or mild AD dementia stages [2], or another constituent of fish could prevent dementia. For instance, fatty fish traditionally consumed in Northern Europe are rich not only in n-3PUFA, but also in vitamin D, which is a recently recognized neurosteroid hormone [3,4]. Vitamin D is essential for neurophysiological function, regulation of neurotransmitters or neurotrophic factors, and cerebral anti-oxydant, anti-inflammatory and antiischemic mechanisms [3,4]. Vitamin D insufficiency may instead cause neuropathological dysfunction such as cognitive impairment. Annweiler et al. [3] recently conducted a systematic literature review on the association of vitamin D status with cognitive status in adults. The five selected cross-sectional studies highlighted an association between low vitamin D concentrations and global cognitive impairment [3], which was subsequently confirmed in more than 750 older community-dwelling women with a twofold higher risk of cognitive impairment for vitamin D deficiency compared to normal status [4]. Vitamin D cognitive implications are also supported by interventional studies, as Dhesi et al. [5] showed in 139 ambulatory older adults that a one-time intramuscular injection of 600 000 UI vitamin D improved the four-choice reaction time compared to placebo after 6 months of follow-up (t = )2.52, P < 0.01). In conclusion, fish consumption appears to prevent dementia. This could be explained by the impact of a health-promoting lifestyle or by the fish itself. In this perspective, the ingestion of omega-3 acids but also of vitamin D should be taken into account.

Arrangement de scripts dans la maladie de Huntington

Resume Le modele theorique du controle de l’action de Norman et Shallice attribue aux noyaux gris centraux un role central dans l’activation et la gestion des schemas d’actions familiers de type script. Dans ce travail, nous avons etudie la capacite de patients atteints d’une maladie de Huntington a reorganiser la chronologie d’actions de scripts donnees avec ou sans actions distractrices (il s’agissait d’actions appartenant a des scripts sans relation avec ceux mis en jeu). Dix patients avec maladie de Huntington symptomatique peu evoluee et 12 sujets controles apparies ont ete evalues. Les patients avec maladie de Huntington ont commis significativement plus d’erreurs de chronologie, mais n’ont pas integre plus de distracteurs que les controles dans leurs arrangements. Ces donnees suggerent l’existence d’un deficit precoce du traitement des sequences sans deficit du traitement des distracteurs chez les patients souffrant de maladie de Huntington. Sur le plan theorique, elles ne s’accordent que partiellement avec les propositions de Norman et Shallice. Sur le plan neuroanatomique, elles sont compatibles avec la proposition d’un declin executif dans la maladie de Huntington affectant d’abord les tâches engageant la boucle striato-dorsale, des travaux anterieurs ayant constate l’existence d’une relation entre troubles de la sequentiation des actions et presence de lesions du cortex frontal dorsolateral.

Cognitive deficits in a suicidal depressed alzheimer's patient: a specific vulnerability?

Dementia has been associated with increased risk of suicide. However, no study has addressed the suicide vulnerability (SV) specifically in people affected by Alzheimer’s disease (AD) (Seyfried et al., 2011), which is the most common form of dementia. Besides, it is thought that neurocognitive dysfunction may facilitate the development of a suicidal crisis during stressful circumstances (i.e., depression) (Jollant et al., 2011). For instance, impairments in cognitive inhibition (Hasher et al., 1999) have been previously implicated in the suicidal crisis among older adults and appeared to be particularly sensitive to aging and depression. We hypothesized that cognitive inhibition could be related to SV regardless of the person’s global cognitive status (i.e., AD or not) and that AD suicidal depressed older patients could have similar cognitive inhibition performance as non-AD suicidal depressed older patients but worse performance than non-suicidal depressed and non-depressed older patients. Our aim was to compare the cognitive inhibition performance in a case report of an Alzheimer’s suicidal depressed patient with four groups of patients: Alzheimer’s non-suicidal non-depressed controls (n=9), non-Alzheimer’s suicidal depressed patients (n=13), non-Alzheimer’s non-suicidal depressed patients (n=12), and non-Alzheimer’s non-suicidal nondepressed controls (n=12), all aged 65 years and older.