Severe Executive Dysfunction Research Articles

Sex, executive function, and prospective memory regulate the chain-mediation pathway of alcohol use and impulsivity.

Evidence from previous studies indicates that impulsive behaviors are closely linked to alcohol use and misuse and that female drinkers are more impulsive than male drinkers. However, studies investigating the psychological mechanisms of alcohol use and impulsivity based on sex differences are relatively limited. This cross-sectional study comprised 713 residents from 16 cities in Anhui Province, China. Each subject was evaluated for self-reporting measures using several questionnaires, including the general information questionnaire, the Alcohol Use Disorders Identification Test (AUDIT), the Prospective and Retrospective Memory Questionnaire (PRM), the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A), and the Barratt Impulsiveness Scale-11 (BIS-11). Executive function and prospective memory may serve as intermediary links between alcohol use and impulsivity. Although the female alcohol usage level was significantly lower than that of males, the female drinkers had more severe executive dysfunction, prospective memory impairment, and impulsivity than male drinkers. Sex moderated the relationship between alcohol use and impulsivity. Furthermore, the indirect effect of executive function, and prospective memory between AUDIT and BIS was more significant in males than in females. Alcohol consumption may be associated with impulsivity formation through executive dysfunction and PM impairment, implying that impulsivity in those with AUD or at risk for AUD might be treated by improving EF and PM. Alcohol use may cause more severe executive dysfunction, PM impairment, and impulsive behavior in females than in males, and impulsive behavior in women with AUD was more likely to be due to the direct effects of alcohol consumption, while impulsive behavior in men with AUD was more likely to be due to the indirect effects of executive dysfunction and PM impairment. These findings provide both clinical and theoretical foundations for addressing issues related to alcohol use.

Identifying subgroups of attention-deficit/hyperactivity disorder from the psychopathological and neuropsychological profiles.

The Research Domain Criteria (RDoC) advocates the dimensional approach in characterizing mental disorders. We followed RDoC to characterize children with ADHD using profiling based on the cognitive and psychopathological domains. We aimed to identify and validate ADHD subtypes with different clinical characteristics and functional impairments. We recruited 362 drug-naïve children with ADHD and 103 typically developing controls. The cluster analysis was used to identify subgroups based on the Child Behaviour Checklist (CBCL) and the Behaviour Rating Inventory of Executive Function (BRIEF). The subgroups' clinical characteristics and functional impairments were assessed using the WEISS Functional Impairment Rating Scale-Parent Report (WFIRS-P) and the Conners Parent Symptom Questionnaire (PSQ). The cluster analysis yielded four subgroups: (1) ADHD with severe impairment in psychopathology and executive functions (EF), (2) ADHD with mild executive dysfunctions and normal-level psychopathology, (3) ADHD with severe externalizing problems and (4) ADHD with severe executive dysfunctions. These subgroups showed different clinical characteristics and degrees of functional impairment. The EF impairment group displayed more serious learning problems and worse life skills than the externalizing group. The two groups with externalizing problems (i.e. the severe impairment group and the externalizing group) both exhibited higher rates of the combined subtype of ADHD and higher rates of comorbid ODD. Different subtypes of ADHD displayed different profiles of internalizing and externalizing problems and levels of executive dysfunctions. In particular, the subtype with severe impairment in EF exhibited more learning problems and worse life skills, suggesting EF is a critical target for intervention in children with ADHD.

Cognitive-Behavioral Social Skills Training for patients with late-life schizophrenia and the moderating effect of executive dysfunction

The objectives of this study are to test the efficacy of Cognitive-Behavioral Social Skills Training (CBSST) in enhancing social function in a sample of older patients with schizophrenia, and to assess whether baseline cognition moderates response to CBSST. To address these objectives, we conducted a randomized controlled trial of 63 participants, randomized 1:1 into CBSST or Treatment-As-Usual (TAU). The setting was a community-based geriatric mental health outpatient clinic in Toronto, Ontario, Canada. Data were collected at baseline, and week 18, 36 and 52, between June 2008 and May 2014. Participants were outpatients, aged 60 or older, with a diagnosis of schizophrenia or schizoaffective disorder and no evidence of dementia or other conditions associated with cognitive or functional impairment. The intervention was a weekly group CBSST for 36 weeks. Cognition, including executive function, was assessed at baseline. Modified total score on the Independent Living Skills Survey (ILSS) at 18, 36, and 52 weeks was the primary outcome measure. In a linear mixed model analysis, the ILSS trajectory was better in the CBSST group than the TAU group, with significantly better function at 36 (Cohen's d = 0.75) and 52 weeks (Cohen's d = 0.92). Baseline executive dysfunction moderated CBSST response, whereby participants with more severe executive dysfunction experienced the most improvement in ILSS. CBSST was efficacious in patients with late-life schizophrenia and prevented decline in social function over a one-year period. CBSST was most beneficial for patients with more severe executive dysfunction, i.e., those who needed skills training the most.

A-66 Neuropsychological Sequalae of SARS-CoV-2

Abstract Objective The purpose of this systematic review is to identify neuropsychological sequelae following infection of SARS-CoV-2. Data Selection A systematic search of the literature was conducted in 2021 using the keywords: neuropsychological symptoms, neuropsychological sequelae, neuropsychological manifestations, SARS-CoV-2, COVID-19, and coronavirus. The search conducted included a total of 6 databases: PsychNet, ProQuest, Taylor & Francis Online, EBSCOhost, Google Scholar, and PubMed Central. A total number of 25 articles were considered, and 8 of those articles were retained. Inclusion criteria consisted of peer-reviewed articles published in English between the years 2020 and 2021. Exclusion criteria consisted of articles not published in English and those that did not examine the neuropsychological symptoms following COVID-19 infection. Data Synthesis Literature examined reported that clinical observations of severe cases of COVID-19 infection were associated with the presence of neuropsychological symptoms. Post-infection of SARS-CoV-2, the following symptoms have been noted: severe executive dysfunction, fluctuations in attention and concentration, and instances of disorientation and confusion. Although etiological hypotheses have been made, there is still no consensus or treatment for the neuropsychological sequelae of COVID-19. Studies also reported that a significant risk factor for these individuals was the presence of premorbid psychological/psychiatric illnesses. Conclusions Patients who recover from severe COVID-19 can experience a multitude of neuropsychological manifestations. In some cases, these effects have been reported to be long-standing. Due to limited understanding regarding the nature and mechanism of action of SARS-CoV-2, it is difficult to pinpoint the cause, duration, treatment, and prognosis of neuropsychological symptoms of post-recovery patients.

Data-driven FDG-PET subtypes of Alzheimer\u2019s disease-related neurodegeneration

BackgroundPrevious research has described distinct subtypes of Alzheimer’s disease (AD) based on the differences in regional patterns of brain atrophy on MRI. We conducted a data-driven exploration of distinct AD neurodegeneration subtypes using FDG-PET as a sensitive molecular imaging marker of neurodegenerative processes.MethodsHierarchical clustering of voxel-wise FDG-PET data from 177 amyloid-positive patients with AD dementia enrolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) was used to identify distinct hypometabolic subtypes of AD, which were then further characterized with respect to clinical and biomarker characteristics. We then classified FDG-PET scans of 217 amyloid-positive patients with mild cognitive impairment (“prodromal AD”) according to the identified subtypes and studied their domain-specific cognitive trajectories and progression to dementia over a follow-up interval of up to 72 months.ResultsThree main hypometabolic subtypes were identified: (i) “typical” (48.6%), showing a classic posterior temporo-parietal hypometabolic pattern; (ii) “limbic-predominant” (44.6%), characterized by old age and a memory-predominant cognitive profile; and (iii) a relatively rare “cortical-predominant” subtype (6.8%) characterized by younger age and more severe executive dysfunction. Subtypes classified in the prodromal AD sample demonstrated similar subtype characteristics as in the AD dementia sample and further showed differential courses of cognitive decline.ConclusionsThese findings complement recent research efforts on MRI-based identification of distinct AD atrophy subtypes and may provide a potentially more sensitive molecular imaging tool for early detection and characterization of AD-related neurodegeneration variants at prodromal disease stages.

Perinatal complications and executive dysfunction in early-onset schizophrenia

BackgroundThe present study examined the association between perinatal obstetric complications and executive dysfunction in early-onset schizophrenia (EOS), compared to healthy controls. Higher incidences of obstetric complications and more severe executive dysfunctions characterize EOS. Research shows extensive brain maturation in newborns, suggesting them to be particularly vulnerable for perinatal insults. Executive function is mainly mediated by the prefrontal cortex, an area that matures last during pregnancy. Thus, exposure to perinatal complications may influence executive dysfunction in EOS.MethodsThe participants were 19 EOS patients and 54 healthy controls. Executive function was assessed with the D-KEFS Color Word Interference Test and the Wisconsin Card Sorting Test. Information on perinatal obstetric complications and Apgar 5-min scores were obtained from the Norwegian Medical Birth Registry. Associations between perinatal conditions and executive function were studied using stepwise regression analyses.ResultsPerinatal complications, and especially shorter gestational lengths, were significantly associated with significant executive dysfunctions in EOS. Perinatal complications did not affect executive function among healthy controls. A significant relationship between lower Apgar 5-min scores and executive dysfunction was found among both EOS patients and healthy controls.ConclusionsExposure to perinatal complications, and particularly a shorter gestational length, was associated with increased executive dysfunction in EOS. Exposed healthy controls did not exhibit similar executive difficulties, suggesting that the EOS patients seemed especially vulnerable for executive deficits due to perinatal insults. The findings indicate that EOS youths learn more slowly and experience more difficulty with problem-solving, which carry important implications for clinical practice. Lower Apgar 5-min scores were associated with executive dysfunction in both groups. Low Apgar score at 5 min may therefore be an important early indicator of executive difficulties among adolescents, independent of diagnosis.

Frontal and subcortical contribution to visual hallucinations in dementia with Lewy bodies and Parkinson’s disease

ABSTRACTObjectives: Visual hallucinations (VH) are common in Lewy body disease (LBD), and have been associated with cognitive and structural brain alterations. Evidence so far concerns mainly Parkinson’s disease (PD), but little is known about symptom-specific pathophysiological mechanisms across the LBD spectrum, especially related to the presence of dementia. The aim of the present pilot study was to investigate the neuroanatomical, and neuropsychological characteristics related to VH in two forms of LBD, namely dementia with Lewy bodies (DLB) and PD without dementia.Methods: Whole brain voxel-based morphometry (VBM) analyses on 3D MRI acquired structural brain scans, and neuropsychological testing were performed on 28 clinically diagnosed DLB (11 with VH, 17 NVH), and 24 PD (9 with VH, and 15 NVH) patients. In order to assess differences in gray matter (GM) regional volumes, and cognitive performance, hallucinating patients for each group were compared with corresponding non-hallucinating ones.Results: DLB patients with VH presented significantly worse visual attention deficits compared to those without, which persisted even when controlling for visual perception. Whole brain VBM analysis revealed decreased GM volume in DLB with VH in the right superior and medial frontal gyri, putamen, caudate nucleus and insula. Subcortical regional volumes were also significantly associated with visual attention performance. Hallucinating PD patients, instead, presented more severe executive dysfunction, but VBM showed no volumetric differences between the two PD subgroups. Post hoc region of interest analyses revealed striatal GM loss in PD with VH.Conclusion: Frontal and striatal GM atrophy may contribute to the emergence of VH in DLB, which may be fostered by the more severe attention deficits. Striatal GM loss and executive dysfunction, instead, appeared to underlie VH in PD without dementia.

Apathy as a herald of cognitive changes in multiple sclerosis: A 2-year follow-up study

Background: Behavioral symptoms, such as apathy and depression, are common in multiple sclerosis (MS) but their relationship with cognitive and clinical characteristics often remains underinvestigated and not monitored over time. Objective: The aim of this study was to assess the evolution of cognitive profile of patients affected by MS in relation to apathy and depression using a 2-year follow-up study. Methods: Two years after the first assessment, 100 of 125 MS patients were re-evaluated on a comprehensive neuropsychological battery, and on specific scales for assessment of apathy (Apathy Evaluation Scale—Self-reported) and depression (Hamilton Depression Rating Scale). Results: After 2 years (T1), we found a relatively consistent prevalence of apathy (about 40%) and a reduction in prevalence of depression (from 44% to 30%). Higher level of apathy at baseline predicted the progressive cognitive changes at follow-up; and patients with apathy without depression (“pure” apathy) than patients without apathy had poorer performance on the interference task of the Stroop test assessing inhibitory control. Conclusion: The present results suggested that apathy in MS was associated with more severe executive dysfunctions (in particular cognitive control). Apathy rather than depression predicted cognitive impairment in MS over time.

Aberrant cerebellar neural activity and cerebro-cerebellar functional connectivity involving executive dysfunction in schizophrenia with primary negative symptoms.

Deficit schizophrenia (DS) is a distinct subtype of schizophrenia characterized by primary and enduring negative symptoms. More severe executive dysfunctions were observed in DS patients, however, the associated neuroimaging characteristics, especially cerebellar functional anomalies in DS, remain largely unknown. We employed resting-state functional and structural MRI data of 106 male participants, including data from 29 DS patients, 39 non-deficit schizophrenia (NDS) patients and 38 healthy controls (HCs). Z-standardized fractional amplitude of low-frequency fluctuation (zfALFF) values were calculated in order to examine spontaneous regional brain activity. Cerebro-cerebellar functional connectivity and changes in the volume of gray matter in the cerebellum were also examined. Relative to the HCs, both DS and NDS patients exhibited decreased zfALFF in the bilateral cerebellar lobules VIII and IX. The zfALFF in the left Crus II was lower in DS patients compared to NDS patients. No significant difference was observed in the volume of cerebellar gray matter among the three groups. Compared with NDS patients, cerebro-cerebellar functional connectivity analysis revealed increased connectivity in the left orbital medial frontal cortex and right putamen regions in DS patients. Reduced zfALFF in the left Crus II in the DS group was significantly positively correlated with Stroop Color and Word scores, while negatively correlated with Trail-Making Test part B scores. The increased functional connectivity in the right putamen in DS patients was significantly positively correlated with Animal Naming Test and semantic Verbal Fluency Test scores. These results highlight cerebellar functional abnormality in DS patients and provide insight into the pathophysiological mechanism of executive dysfunction.

Vitamin K Antagonists and Cognitive Decline in Older Adults: A 24-Month Follow-Up.

Vitamin K participates in brain physiology. This study aimed to determine whether using vitamin K antagonists (VKAs), which interfere with the vitamin K cycle, were (i) cross-sectionally associated with altered cognitive performance, and (ii) independent predictors of cognitive changes in older adults over 24 months. Information was collected on the use of VKAs (i.e., warfarin, acenocoumarol, and fluindione) among 378 geriatric outpatients (mean, 82.3 ± 5.6 years; 60.1% female). Global cognitive performance and executive functions were assessed with Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB) scores, respectively, at baseline and after 12 and 24 months of follow-up. Age, gender, body mass index, mean arterial pressure, disability, gait speed, comorbidities, atrial fibrillation, stroke, carotid artery stenosis, leukoaraiosis grade on computed tomography (CT) scan, psychoactive drugs, antidementia drugs, blood-thinning drugs (i.e., anticoagulants other than VKAs, antiplatelet medications), serum creatinine levels, and vitamin B12 concentrations were considered as potential confounders. Using VKAs was associated with lower (i.e., worse) FAB score at baseline (adjusted β = −2.1, p = 0.026), and with a decrease in FAB score after 24 months (adjusted β = −203.6%, p = 0.010), but not after 12 months (p = 0.659). Using VKAs was not associated with any change in MMSE score at baseline (p = 0.655), after 12 months (p = 0.603), or after 24 months (p = 0.201). In conclusion, we found more severe executive dysfunction at baseline and incident executive decline over 24 months among geriatric patients using VKAs, when compared with their counterparts.

Cognitive correlates of “pure apathy” in Parkinson's disease

IntroductionPrevious studies exploring the association between apathy and cognitive deficits in Parkinson's disease (PD) employed scales and questionnaires for apathy, which did not control for the possible confounding effect of motor symptoms. Here we investigated the cognitive correlates of “pure apathy” by the Dimensional Apathy Scale, which allows us to assess apathy minimizing the influence of motor symptoms. MethodsConsecutive PD outpatients referred to our centre were screened. All participants underwent a neuropsychological battery to assess verbal memory, executive functions and visuospatial abilities, apathy and depressive symptoms. ResultsWe enrolled 56 non-depressed and non-demented PD patients, of whom 28 were apathetic and 28 were not. The two groups did not differ on demographic and clinical aspects; apathetic PD patients performed worse than non-apathetic PD patients on the part A, B and B-A of Trail Making Test and the interference task of Stroop test. No significant differences were found on memory and perceptual visuospatial tasks. ConclusionsOur results demonstrated that “pure apathy” is associated with more severe executive dysfunctions such as alteration of set-shifting and inhibitory control, which are mediated by prefrontal cortex and subcortical regions (i.e. basal ganglia). Our findings also supported the hypothesis that co-occurrence of apathy and executive deficits may be the epiphenomenon of damage in prefrontal-striatal cortical circuitries connecting dorsolateral prefrontal cortex, anterior cingulate cortex and basal ganglia.

Assessment of executive functions in children and adolescents with acquired brain injury (ABI) using a novel complex multi-tasking computerised task: The Jansari assessment of Executive Functions for Children (JEF-C©)

ABSTRACTObjectives: The Jansari assessment of Executive Functions for Children (JEF-C©) is a new non-immersive computerised assessment of executive functions. The objectives of the study were to test the feasibility and validity of JEF-C© in children and adolescents with acquired brain injury (ABI).Methods: Twenty-nine patients with ABI aged 10–18 years and 30 age-and gender-matched controls were tested. Participants performed JEF-C©, Wechsler Abbreviated Scale of Intelligence (WASI) and the Behavioural Assessment of the Dysexecutive Syndrome for Children (BADS-C), while parents completed the Behaviour Rating Inventory of Executive Function (BRIEF) questionnaire.Results: The JEF-C© task proved feasible in patients with ABI. The internal consistency was medium (Cronbach’s alpha = 0.62 and significant intercorrelations between individual JEF-C© constructs). Patients performed significantly worse than controls on most of the JEF-C© subscales and total score, with 41.4% of participants with ABI classified as having severe executive dysfunction. No significant correlations were found between JEF-C© total score, the BRIEF indices, and the BADS-C. Significant correlations were found between JEF-C© and demographic characteristics of the sample and intellectual ability, but not with severity/medical variables.Conclusion: JEF-C© is a playful complex task that appears to be a sensitive and ecologically valid assessment tool, especially for relatively high-functioning individuals.

Apolipoprotein Eε4: A Biomarker for Executive Dysfunction among Parkinson's Disease Patients with Mild Cognitive Impairment.

Background: Cognitive impairment is prevalent in Parkinson's disease (PD), affecting 15–20% of patients at diagnosis. α-synuclein expression and genetic polymorphisms of Apolipoprotein E (ApoE) have been associated with the presence of cognitive impairment in PD although data have been inconsistent.Objectives: To determine the prevalence of cognitive impairment in patients with PD using Montreal Cognitive Assessment (MoCA), Comprehensive Trail Making Test (CTMT) and Parkinson's disease-cognitive rating scale (PDCRS), and its association with plasma α-synuclein and ApoE genetic polymorphisms.Methods: This was across-sectional study involving 46 PD patients. Patients were evaluated using Montreal cognitive assessment test (MoCA), and detailed neuropsychological tests. The Parkinson's disease cognitive rating scale (PDCRS) was used for cognitive function and comprehensive trail making test (CTMT) for executive function. Blood was drawn for plasma α-synuclein measurements and ApoE genetic analysis. ApoE polymorphism was detected using MutaGELAPoE from ImmunDiagnostik. Plasma α-synuclein was detected using the ELISA Technique (USCN Life Science Inc.) according to the standard protocol.Results: Based on MoCA, 26 (56.5%) patients had mild cognitive impairment (PD-MCI) and 20 (43.5%) had normal cognition (PD-NC). Based on the PDCRS, 18 (39.1%) had normal cognition (PDCRS-NC), 17 (37%) had mild cognitive impairment (PDCRS-MCI), and 11 (23.9%) had dementia (PDCRS-PDD). In the PDCRS-MCI group, 5 (25%) patients were from PD-NC group and all PDCRS-PDD patients were from PD-MCI group. CTMT scores were significantly different between patients with MCI and normal cognition on MoCA (p = 0.003). Twenty one patients (72.4%) with executive dysfunction were from the PD-MCI group; 17 (77.3%) with severe executive dysfunction and 4 (57.1%) had mild to moderate executive dysfunction. There were no differences in the plasma α-synuclein concentration between the presence or types of cognitive impairment based on MoCA, PDCRS, and CTMT. TheApoEe4 allele carrier frequency was significantly higher in patients with executive dysfunction (p = 0.014).Conclusion: MCI was prevalent in our PD population. PDCRS appeared to be more discriminatory in detecting MCI and PDD than MoCA. Plasma α-synuclein level was not associated with presence nor type of cognitive impairment, but the ApoEe4 allele carrier status was significantly associated with executive dysfunction in PD.

FV 12 Longitudinal study on hippocampal volume and neuropsychological outcome in IgM-NMDAR-antibody-associated encephalopathy

Introduction Anti-NMDAR-IgM-autoantibodies (IgM-NMDAR-aab) are occurring in approximately 4–5% of the general population ( Dahm et al., 2014 ). IgM-NMDAR-aab are also associated to a rare encephalopathy presenting with symptoms resembling fronto-temporal dementia (FTD) but with much faster progression as a neurodegenerative disease ( Doss et al., 2014 ). Treatment with an immunosuppressive therapy is recommend but has not been evaluated with neuroimaging and neuropsychology. Here, we present longitudinal data on two cases. Methods We identified two patients referred to us presenting memory disturbances and memory loss together with a severe executive dysfunction and alteration in behavior developing within 3–5 months. CSF did not reveal an Alzheimer’s-disease like constellation. Routine MRI scans were considered normal. Neuropsychological testing showed severe deficits in fronto-temporal functioning. Antibody screening via indirect immunofluorescence test (IFT) involved IgM-, IgA- and IgG-NMDAR-ab, Lgi-1-, CASPR2-, DPPX- and AMPA-IgG-ab and also onconeuronal ab via an immunoblot analysis (anti-Hu, -Yo, -Ri, -CV2, -Ma2, -Amphiphysin, -GAD65, -Tr(DNER), -Sox1, -Titin and -Recoverin-ab; all tests were performed by Euroimmun, Lubeck, Germany). Both patients received multiple methylprednisolone (MP) i.v. therapies (each cycle with 1 g i.v. per day for 3 days for a total of 9 g MP(Pat1) or 15 g MP(Pat2)). MRI scans were conducted during therapy and after therapy. Data were acquired on a 3-Tesla MR scanner (Siemens MAGNETOM Prisma, Erlangen, Germany) equipped with a 20-channel head coil. T1-weighted, high-resolution structural MR-images were obtained using a three dimensional MPRAGE sequence yielding an isotropic resolution of 1 mm 3 . Hippocampal volume was manually assessed via Multitracer software (free software, UCLA, USA) and double-checked. Neuropsychological assessment was identically performed for each patient during each assessment time point (Rey-Figure, Trail making test A/B, executive and memory test, digit and word-span). Results Serum titers were highly pathological for path patients, with Pat1 having an IgM-NMDAR-aab titer of 1:160 and Pat2 of 1:320. No other abs were detected via immunoblot or IFT. In addition, results of manual assessment revealed that hippocampal (HC) volume increased bilaterally in Pat1 due to MP-treatment. Accordingly, neuropsychological measures of memory function (digit span, Rey-figure) improved slightly in Pat1. In Pat2, in contrast, only the right HC had a slight volume increase, while the left HC volume showed a slight decrease. Nevertheless, initial memory dysfunctions observed in Pat2 declined remarkably in the course of our treatment. Beyond that, clinical assessment showed an overall improvement in Pat1 and in Pat2 a complete recovery after intravenous MP-treatment. Discussion Here, we show the first longitudinal follow-up of NMDA-aab associated encephalopathy. Treatment with MP resulted in a good to excellent improvement of clinical as well as neuropsychological assessment. These functional measures, however, were only partially mirrored by HC volume alterations during the course of the treatment. In cases of unclear dementia-like symptoms NMDAR-aab associated encephalopathy should be taken into account and treated with immunosuppressives.

Cognitive sequelae of methanol poisoning involve executive dysfunction and memory impairment in cross-sectional and long-term perspective.

Methanol poisoning leads to lesions in the basal ganglia and subcortical white matter, as well as to demyelination and atrophy of the optic nerve. However, information regarding cognitive deficits in a large methanol sample is lacking. The principal aim of the present study was to identify the cognitive sequelae of methanol poisoning and their morphological correlates. A sample of 50 patients (METH; age 48±13 years), 3-8 months after methanol poisoning, and 57 control subjects (CS; age 49±13 years) were administered a neuropsychological battery. Forty-six patients were followed in 2 years' perspective. Patients additionally underwent 1.5T magnetic resonance imaging (MRI). Three biochemical and toxicological metabolic markers and a questionnaire regarding alcohol abuse facilitated the classification of 24 patients with methanol poisoning without alcohol abuse (METHna) and 22 patients with methanol poisoning and alcohol abuse (METHa). All groups were compared to a control group of similar size, and matched for age, education, premorbid intelligence level, global cognitive performance, and level of depressive symptoms. Using hierarchical multiple regression we found significant differences between METH and CS, especially in executive and memory domains. METHa showed a similar pattern of cognitive impairment with generally more severe executive dysfunction. Moreover, all METH patients with extensive involvement on brain MRI (lesions in ≥2 anatomical regions) had a more severe cognitive impairment. From a longitudinal perspective, we did not find any changes in their cognitive functioning after 2 years' follow-up. Our findings suggest that methanol poisoning is associated with executive dysfunction and explicit memory impairment, supposedly due to basal ganglia dysfunction and disruption of frontostriatal circuitry proportional to the number of brain lesions, and that these changes are persistent after 2 years' follow-up.

The effect of contextual auditory stimuli on virtual spatial navigation in patients with focal hemispheric lesions

ABSTRACTTopographical disorientation is a frequent deficit among patients suffering from brain injury. Spatial navigation can be explored in this population using virtual reality environments, even in the presence of motor or sensory disorders. Furthermore, the positive or negative impact of specific stimuli can be investigated. We studied how auditory stimuli influence the performance of brain-injured patients in a navigational task, using the Virtual Action Planning–Supermarket (VAP-S) with the addition of contextual (“sonar effect” and “name of product”) and non-contextual (“periodic randomised noises”) auditory stimuli. The study included 22 patients with a first unilateral hemispheric brain lesion and 17 healthy age-matched control subjects. After a software familiarisation, all subjects were tested without auditory stimuli, with a sonar effect or periodic random sounds in a random order, and with the stimulus “name of product”. Contextual auditory stimuli improved patient performance more than control group performance. Contextual stimuli benefited most patients with severe executive dysfunction or with severe unilateral neglect. These results indicate that contextual auditory stimuli are useful in the assessment of navigational abilities in brain-damaged patients and that they should be used in rehabilitation paradigms.

Characteristics of Alzheimer's Disease Patients with Severe Executive Disorders.

Executive dysfunctions in Alzheimer's disease (AD) have been assessed using variable batteries and/or in selected populations. The primary objective of this observational study was to determine the prevalence and severity of executive dysfunction in AD patients using a previously validated battery. The secondary objective was to determine the characteristics including treatment outcomes of AD patients with severe executive dysfunction. The study included AD patients with mild-to-moderate dementia aged 60 or over, consulting in various clinical settings including memory clinics and requiring the introduction of an antidementia drug. Executive dysfunction was examined using a validated, shortened executive battery. 381 patients were included. Executive dysfunctions were observed in 88.2% of the patients (95% CI: 84.9-91.4) and were severe (defined as ≥2/3 impaired scores) in 80.4% (95% CI: 76.9-84.8). Global hypoactivity with apathy was more frequent (p = 0.0001) than impairment in executive function tests. The 308 patients with severe executive dysfunction were older (p = 0.003) and had more severe dementia (p = 0.0001). Similarly, in the subset of 257 patients with mild dementia, individuals with severe executive dysfunction were older (p = 0.003) and had more severe dementia. Global hypoactivity was independently associated with difficulties in IADL and a higher caregiver burden (p = 0.0001 for both). The severity of executive dysfunction did not significantly influence the patients' outcomes at 6 months. Executive dysfunction is a very common disorder in a representative population of patients with mild-to-moderate AD. It was independently correlated with impaired autonomy and increased caregiver burden but did not significantly influence treatment outcomes.

Progression of neuropsychiatric and cognitive features due to exons 2 to 5 deletion in the epsilon-sarcoglycan gene: a case report

ABSTRACTPhysical symptoms of myoclonus dystonia due to epsilon-sarcoglycan mutations are well documented; however, the progression of neuropsychiatric and cognitive symptoms remains unclear. We present a case of a 34-year-old woman with early childhood onset of myoclonic jerks, dystonic posture and developmental delay due to exons 2 to 5 deletion in the epsilon-sarcoglycan gene. Over time, she developed neuropsychiatric symptoms. She underwent bilateral deep brain stimulation of the ventral intermediate nucleus of the thalamus for her motor symptoms, which greatly improved but she exhibited slow deterioration of her neuropsychiatric and cognitive symptoms, particularly apathy, aggression and severe executive dysfunction.

Behavioral Intervention for Chronic Perseverative Speech After Brain Injury

To investigate the effects of a specific behavioral intervention on the rate of perseverations in a subject with chronic and severe executive dysfunction following traumatic brain injury.

Dementia does not Preclude Very Reliable Responding on the MMPI-2 RF: A Case Report

The Minnesota Multiphasic Personality Inventory (MMPI) family of personality tests has long been used by psychologists, in part because it provides extensive information on the validity of patient responses. Although much of the research on MMPI validity indicators has focused on over-reporting or under-reporting symptoms, the consistency (i.e., reliability, a requirement for validity) of responding is also critical to examine. Clinicians tend to avoid using the MMPI-2 or the MMPI-2-RF (Restructured Form) in patients with dementia based on the belief that severe cognitive impairment would make reliable responding impossible given the large number of items (567 and 338, respectively). In contrast with this belief we present the case of a 65-year-old woman with severe memory impairments and executive dysfunction due to a non-specific dementia syndrome who was able to provide remarkably consistent responding on the MMPI-2-RF. Implications and future directions are discussed.