Valérie Chauviré

Vitamin D and ageing: neurological issues.

Objective: Vitamin D has been shown to have multiple biological targets mediated by the vitamin D receptor present in many cells. Specific actions on the central nervous system (CNS) have been described. The objective of this review was to describe the relationship between vitamin D and the nervous system throughout the different stages of life. Methods: A bibliographical search was performed in the MedLine and Cochrane library databases. The keywords used were: ‘vitamin D’ and ‘nervous system’ and/or ‘central nervous system’ and/or ‘nervous system diseases’ and/or ‘psychological tests’ and/or ‘neuropsychological tests’ and/or ‘mental disorders’. The search period ranged from 01/01/1988 to 31/10/2009. Two hundred and ninety-five abstracts were first identified after screening. A final selection of 127 articles was used for the purpose of this review. Results: The studies published over the past 20 years provide an increasing number of arguments in favor of a life-long role of vitamin D on the nervous system as a whole, and in particular on the CNS. During cerebral development, vitamin D may act like a neurosteroid hormone in the areas of neurotransmission, neuroprotection, and neuroimmunomodulation. Moreover, vitamin D deficiency has been associated with neurological and psychiatric disorders. In older adults, hypovitaminosis D has been associated with neuromuscular disorders, dementia, and Parkinson’s disease. Thus, vitamin D supplementation might have a protective effect against these neurological disorders. Conclusions: Vitamin D has been associated with many neurological functions and its deficiency with dysfunction. Low serum 25-hydroxyvitamin D concentrations can potentially be reversed. This simple and low-cost correction might contribute to the primo-secondary prevention of various neuropsychiatric disorders.

Apraxia of tool use: More evidence for the technical reasoning hypothesis

Various distinct cognitive processes such as semantic memory, executive planning or technical reasoning have been shown to support tool use. The aim of this study is to investigate the relationship between these processes. To do so, a large apraxia battery was submitted to 16 patients with left brain-damage (LBD) and aphasia and 19 healthy controls. The battery included: classical apraxia tests (Pantomime of Tool Use and Single Tool Use), familiar and novel tool use tests (Tool-Object Pairs and Sequential Mechanical Problem-Solving), semantic memory tests (Recognition of tool utilization gestures and Functional and Categorical Associations) as well as the Tower Of London. The Sequential Mechanical Problem-Solving task is a new task which permits the evaluation of pre-planning in unusual tool use situations. In this task as well as in the Tool-Object Pairs task, participants solved a tool use problem in a Choice and a No-Choice condition to examine the effect of tool selection. Globally, left brain damaged patients were impaired as compared to controls. We found high correlations in left brain damaged patients between performances on classical apraxia tests, familiar and novel tool use tests and Functional and Categorical Associations but no significant association between these performances and Tower Of London or Recognition of tool utilization gestures. Furthermore, the two conditions (Choice and No-Choice) of Tool-Object Pairs and Sequential Mechanical Problem-Solving were associated. In sum, all tasks involving tool use are strongly associated in LBD patients. Moreover, the ability to solve sequential mechanical problems does not depend on executive planning. Also, tool use appears to be associated with knowledge about object function but not with knowledge about tool manipulation. Taken together, these findings indicate that technical reasoning and, to a lesser extent, semantic memory may both play an important role in tool use.

APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases

Background Amyloid protein precursor (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2) mutations cause autosomal dominant forms of early-onset Alzheimer disease (AD-EOAD). Although these genes were identified in the 1990s, variant classification remains a challenge, highlighting the need to colligate mutations from large series. Methods and findings We report here a novel update (2012–2016) of the genetic screening of the large AD-EOAD series ascertained across 28 French hospitals from 1993 onwards, bringing the total number of families with identified mutations to n = 170. Families were included when at least two first-degree relatives suffered from early-onset Alzheimer disease (EOAD) with an age of onset (AOO) ≤65 y in two generations. Furthermore, we also screened 129 sporadic cases of Alzheimer disease with an AOO below age 51 (44% males, mean AOO = 45 ± 2 y). APP, PSEN1, or PSEN2 mutations were identified in 53 novel AD-EOAD families. Of the 129 sporadic cases screened, 17 carried a PSEN1 mutation and 1 carried an APP duplication (13%). Parental DNA was available for 10 sporadic mutation carriers, allowing us to show that the mutation had occurred de novo in each case. Thirteen mutations (12 in PSEN1 and 1 in PSEN2) identified either in familial or in sporadic cases were previously unreported. Of the 53 mutation carriers with available cerebrospinal fluid (CSF) biomarkers, 46 (87%) had all three CSF biomarkers—total tau protein (Tau), phospho-tau protein (P-Tau), and amyloid β (Aβ)42—in abnormal ranges. No mutation carrier had the three biomarkers in normal ranges. One limitation of this study is the absence of functional assessment of the possibly and probably pathogenic variants, which should help their classification. Conclusions Our findings suggest that a nonnegligible fraction of PSEN1 mutations occurs de novo, which is of high importance for genetic counseling, as PSEN1 mutational screening is currently performed in familial cases only. Among the 90 distinct mutations found in the whole sample of families and isolated cases, definite pathogenicity is currently established for only 77%, emphasizing the need to pursue the effort to classify variants.

Mechanical problem-solving strategies in Alzheimer's disease and semantic dementia.

OBJECTIVE The goal of this study was to explore whether the tool-use disorders observed in Alzheimers disease (AD) and semantic dementia (SD) are of the same nature as those observed in left brain-damaged (LBD) patients. Recent evidence indicates that LBD patients with apraxia of tool use encounter difficulties in solving mechanical problems, characterized by the absence of specific strategies. This pattern may show the presence of impaired mechanical knowledge, critical for both familiar and novel tool use. So, we explored the strategies followed by AD and SD patients in mechanical problem-solving tasks in order to determine whether mechanical knowledge is also impaired in these patients. METHOD We used a mechanical problem-solving task in both choice (i.e., several tools were proposed) and no-choice (i.e., only 1 tool was proposed) conditions. We analyzed quantitative data and strategy profiles. RESULTS AD patients but not SD patients met difficulties in solving mechanical problem-solving tasks. However, the key finding is that AD patients, despite their difficulties, showed strategy profiles that are similar to that of SD patients or controls. Moreover, AD patients exhibited a strategy profile distinct from the one previously observed in LBD patients. CONCLUSIONS Those observations lead us to consider that difficulties met by AD patients to solve mechanical problems or even to use familiar tools may not be caused by mechanical knowledge impairment per se. In broad terms, what we call apraxia of tool use in AD is certainly not the same as apraxia of tool use observed in LBD patients. (PsycINFO Database Record

The neural substrates of script knowledge deficits as revealed by a PET study in Huntington's disease.

INTRODUCTION Previous neuropsychological investigations have suggested that both the prefrontal cortex and the basal ganglia are involved in the management of script event knowledge required in planning behavior. METHODS This study was designated to map, the correlations between resting-state brain glucose utilization as measured by FDG-PET (positron emission tomography) and scores obtained by means of a series of script generation and script sorting tasks in 8 patients with early Huntingtons disease. RESULTS These patients exhibited a selectively greater impairment for the organizational aspects of scripts compared to the semantic aspects of scripts. We showed significant negative correlations between the number of sequencing, boundary, perseverative and intrusion errors and the metabolism of several cortical regions, not only including frontal, but also posterior regions. CONCLUSION Our findings suggest that, within the fronto-striatal system, the cortical frontal regions are more crucial in script retrieval and script sequencing than the basal ganglia.

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.

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

Although 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 = 19) and early AD (eAD) patients (n = 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.

An integrative view of Luria’s perspective on arithmetic problem solving: The two sides of environmental dependency

Introduction: A. R. Luria was the first author to hypothesize that executive dysfunction can lead to specific deficits in arithmetic problem solving, showing that patients’ performance depends on the structure of the tasks. Cummings (1995. Anatomic and behavioral aspects of frontal-subcortical circuits. Annals of the New York Academy of Sciences, 15, 1–13) proposed the term “environmental dependency” to define such behavioral disorders triggered by the characteristics of the test and pointed out also the role of executive impairments. Few studies compare executive functioning and problem solving in brain-damaged patients, and none have examined the question from this point of view. Thus, the main aim of the present paper was to study the relationship between environmental dependency and executive functions. Method: Fifty neurological patients with frontal, subcortical, and posterior brain lesions were compared to 45 matched healthy controls and were divided into two groups (dysexecutive/nondysexecutive) according to their performances on executive tasks. Then, we confronted the results of the two groups on an experimental protocol designed in accordance with Luria’s proposals. We made also comparisons between groups on the basis of lesion location. Results: Our findings indicate a high association between executive functions and environmental dependency, showing that dysexecutive patients’ performances were dependent on task demands. In addition, a specific frontal behavior not associated with executive functions and characterized by the solving of insoluble problems was highlighted. Conclusion: The discussion focused on the interest to take into account the methodological and clinical contributions of environmental dependency. Based on our findings and theoretical arguments, we highlight the need to fractionate this concept.

Frontal versus dysexecutive syndromes: relevance of an interactionist approach in a case series of patients with prefrontal lobe damage.

ABSTRACT The concepts of “frontal” and “dysexecutive” syndromes are still a matter of debate in the literature. These terms are often used interchangeably but can be distinguished when considering specific frontal behavioural deficits which occur during social interaction. Despite being of interest for the clinical assessment and care management of patients with anterior brain damage, few studies have tried to disentangle the specificity of each syndrome. We report the case of eight patients with frontal lobe damage who were assigned to one of two groups based on whether or not they showed a dysexecutive syndrome. The nondysexecutive group differed from the dysexecutive group in showing environmental dependency phenomena, behavioural disorders triggered by social interaction. By adopting an interactionist perspective, this pilot study contributes to defining more precisely the distinction between “frontal” and “dysexecutive” syndromes. The discussion focuses on the potential interest of the interactionist approach in designing appropriate methodologies of assessment and rehabilitation of patients with frontal lobe syndrome.

Rethinking the Cognitive Mechanisms Underlying Pantomime of Tool Use: Evidence from Alzheimer's Disease and Semantic Dementia.

OBJECTIVES Pantomiming the use of familiar tools is a central test in the assessment of apraxia. However, surprisingly, the nature of the underlying cognitive mechanisms remains an unresolved issue. The aim of this study is to shed a new light on this issue by exploring the role of functional, mechanical, and manipulation knowledge in patients with Alzheimers disease and semantic dementia and apraxia of tool use. METHODS We performed multiple regression analyses with the global performance and the nature of errors (i.e., production and conception) made during a pantomime of tool use task in patients and control participants as dependent variables and tasks investigating functional, mechanical, and manipulation knowledge as predictors. RESULTS We found that mechanical problem solving, assessing mechanical knowledge, was a good predictor of the global performance of pantomime of tool use. We also found that occurrence of conception errors was robustly predicted by the task assessing functional knowledge whereas that of production errors was not explained by only one predictor. CONCLUSIONS Our results suggest that both functional and mechanical knowledge are important to pantomime the use of tools. To our knowledge, this is the first demonstration that mechanical knowledge plays a role in pantomime of tool use. Although impairment in pantomime of tool use tasks (i.e., apraxia) is widely explained by the disruption of manipulation knowledge, we propose that pantomime of tool use is a complex problem-solving task. (JINS, 2017, 23, 128-138).