Persistent Cognitive Deficits Research Articles

Alpha event-related decreases during encoding in adults with ADHD – An investigation of sustained attention and working memory processes

BackgroundExecutive functioning deficits are central to established neuropsychological models of ADHD. Oscillatory activity, particularly the alpha rhythm (8–12 Hz) has been associated with cognitive impairments in ADHD. However, most studies to date examined such neural mechanisms underlying executive dysfunction in children and adolescents with ADHD, raising the question of whether and to what extent those ADHD-related working memory impairments are still present in adults. To this end, the current study aimed to investigate the role of alpha event-related decreases (ERD) during working memory processes in adults with and without ADHD. MethodsWe collected electroencephalographic (EEG) data from 85 adults with a lifetime diagnosis of ADHD and 105 controls (aged 32–64), while they performed a continuous performance (CPT) and a spatial delayed response working memory task (SDRT). Time-frequency and independent component analysis (ICA) was used to identify alpha (8–12 Hz) clusters to examine group and condition effects during the temporal profile of sustained attention and working memory processes (encoding, maintenance, retrieval), loads (low and high) and trial type (go and nogo). ResultsIndividuals with ADHD exhibited higher reaction time-variability in SDRT, and slower response times in SDRT and CPT, despite no differences in task accuracy. Although working memory load was associated with stronger alpha ERD in both tasks and both groups (ADHD, controls), we found no consistent evidence for attenuated alpha ERD in adults with ADHD, failing to replicate effects reported in children. In contrast, when looking at the whole sample, the correlations of alpha power during encoding with inattention and hyperactivity-impulsivity symptoms were significant, replicating prior findings in children with ADHD, but suggesting an alternate source for these effects in adults. ConclusionsOur results corroborate the robustness of alpha as a marker of visual attention and suggest that occipital alpha ERD normalizes in adulthood, but with unique contributions of centro-occipital alpha ERD, suggesting a secondary source. This implies that deviations in processes other than previously reported visuospatial cortex engagement may account for the persistent symptoms and cognitive deficits in adults with a history of ADHD.

Neurological, psychiatric, and sleep investigations after treatment of anti-leucine-rich glioma-inactivated protein 1 (LGI1) encephalitis in Spain: a prospective cohort study

Anti-leucine-rich glioma-inactivated protein 1 (LGI1) encephalitis is an autoimmune disorder that can be treated with immunotherapy, but the symptoms that remain after treatment have not been well described. We aimed to characterise the clinical features of patients with anti-LGI1 encephalitis for 1 year starting within the first year after initial immunotherapy. For this prospective cohort study, we recruited patients with anti-LGI1 encephalitis as soon as possible after they had received conventional immunotherapy for initial symptoms; patients were recruited from 21 hospitals in Spain. Patients were excluded if they had an interval of more than 1 year since initial immunotherapy, had pre-existing neurodegenerative or psychiatric disorders, or were unable to travel to Hospital Clínic de Barcelona (Barcelona, Spain). Patients visited Hospital Clínic de Barcelona on three occasions-the first at study entry (visit 1), the second 6 months later (visit 2), and the third 12 months after the initial visit (visit 3). They underwent neuropsychiatric and videopolysomnography assessments at each visit. Healthy participants who were matched for age and sex and recruited from Hospital Clínic de Barcelona underwent the same investigations at study entry and at 12 months. Cross-sectional comparisons of clinical features between groups were done with conditional logistic regression, and binary logistic regression was used to assess associations between cognitive outcomes at 12 months and clinical features before initial immunotherapy and at study entry. Between May 1, 2019, and Sept 30, 2022, 42 participants agreed to be included in this study. 24 (57%) participants had anti-LGI1 encephalitis (mean age 63 years [SD 12]; 13 [54%] were female and 11 [46%] were male) and 18 (43%) were healthy individuals (mean age 62 years [10]; 11 [61%] were female and seven [39%] were male). At visit 1 (median 88 days [IQR 67-155] from initiation of immunotherapy), all 24 patients had one or more symptoms; 20 (83%) patients had cognitive deficits, 20 (83%) had psychiatric symptoms, 14 (58%) had insomnia, 12 (50%) had rapid eye movement (REM)-sleep behaviour disorder, nine (38%) had faciobrachial dystonic seizures, and seven (29%) had focal onset seizures. Faciobrachial dystonic seizures were unnoticed in four (17%) of 24 patients and focal onset seizures were unnoticed in five (21%) patients. At visit 1, videopolysomnography showed that 19 (79%) patients, but no healthy participants, had disrupted sleep structure (p=0·013); 15 (63%) patients and four (22%) healthy participants had excessive fragmentary myoclonus (p=0·039), and nine (38%) patients, but no healthy participants, had myokymic discharges (p=0·0051). These clinical and videopolysomnographic features led to additional immunotherapy in 15 (63%) of 24 patients, which resulted in improvement of these features in all 15 individuals. However, at visit 3, 13 (65%) of 20 patients continued to have cognitive deficits. Persistent cognitive deficits at visit 3 were associated with no use of rituximab before visit 1 (odds ratio [OR] 4·0, 95% CI 1·5-10·7; p=0·0015), REM sleep without atonia at visit 1 (2·2, 1·2-4·2; p=0·043), and presence of LGI1 antibodies in serum at visit 1 (11·0, 1·1-106·4; p=0·038). Unsuspected but ongoing clinical and videopolysomnography alterations are common in patients with anti-LGI1 encephalitis during the first year or more after initial immunotherapy. Recognising these alterations is important as they are treatable, can be used as outcome measures in clinical trials, and might influence cognitive outcome. Fundació La Caixa.

Abstract WP221: Vein of Galen Malformations: Twenty Years Later

Introduction: Vein of Galen Malformations (VOGM) are congenital arteriovenous malformations which carry a mortality of 76.7% in untreated patients. Outcomes have improved over time with advances in endovascular embolization. As endovascular management of VOGM has begun to favor more aggressive treatment strategies, there is scarce literature examining long-term functional and neurological outcomes and whether patients may have benefited from a more or less aggressive approach to treatment. Methods: A single-center retrospective review identified all patients with VOGM over the age of 18 with complete clinical data from January 1982 to May 2005. Patients were stratified based on radiographic outcomes: cured before the age of 18 (“pediatric-cured group”), cured after the age of 18, or not cured. Patients cured after the age of 18 and patients who were never cured were grouped together (“adult-cured group”). Long-term functional outcomes were assessed using the modified Rankin Scale (mRS). Statistical analyses were conducted in R version 4.2.1. Results: Forty-three adult patients were identified: 26 in the pediatric-cured group and 17 in the adult-cured group. The median current age of the pediatric-cured group was less than the adult-cured group (21 vs. 28, p<0.01). On initial presentation, the groups did not differ in their clinical or radiographic symptoms, comorbidities, or developmental delays. No significant differences were present in treatment courses. The pediatric-cured group demonstrated lower risk of intraprocedural or postprocedural hemorrhagic complications (p=0.03). On long-term follow-up, adult-cured patients presented with worse mRS (p<0.01), a higher rate of neurological symptoms (p<0.01), persistent fine motor delays (p<0.03), persistent cognitive or learning deficits (p=0.04), and persistent hydrogenous disorder (p<0.01). Conclusion: This is the first study to analyze long-term outcomes of adult patients managed for VOGM during the pediatric period. Patients cured in the pediatric period demonstrated reduced risk of hemorrhagic complications and improved long-term functional and neurological outcomes. Pursuing early cure in patients with VOGM may provide long-term benefit and reduce risk in later treatment.

The effect of intranasal oxytocin on neurocognition in people with schizophrenia: A randomized controlled trial

Schizophrenia is characterized by persistent cognitive deficits that significantly impact functional outcomes. Despite the current available treatments, these deficits remain inadequately addressed, highlighting the need to explore the effect of more novel treatments on cognition. The current study examined the effect of intranasal oxytocin on cognitive functioning in people with schizophrenia by utilizing data from a 12-week, randomized controlled trial. Sixty-seven participants with schizophrenia or schizoaffective disorder were randomized to receive placebo or intranasal oxytocin. Participants completed a comprehensive neuropsychological battery at baseline and 12 weeks. The results demonstrated that intranasal oxytocin did not significantly improve cognition in people with schizophrenia compared to placebo. These findings suggest that oxytocin does not worsen or enhance cognition in people with schizophrenia. Yet, the current intervention did not standardize the timing of cognitive assessments relative to the timing of oxytocin administration, which may explain our findings. Future studies attempting to clarify this relationship would benefit from employing a more controlled approach to the timing of treatment and assessments.

Clinical Outcomes After Traumatic Brain Injury and Exposure to Extracranial Surgery

Traumatic brain injury (TBI) is associated with persistent functional and cognitive deficits, which may be susceptible to secondary insults. The implications of exposure to surgery and anesthesia after TBI warrant investigation, given that surgery has been associated with neurocognitive disorders. To examine whether exposure to extracranial (EC) surgery and anesthesia is related to worse functional and cognitive outcomes after TBI. This study was a retrospective, secondary analysis of data from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study, a prospective cohort study that assessed longitudinal outcomes of participants enrolled at 18 level I US trauma centers between February 1, 2014, and August 31, 2018. Participants were 17 years or older, presented within 24 hours of trauma, were admitted to an inpatient unit from the emergency department, had known Glasgow Coma Scale (GCS) and head computed tomography (CT) status, and did not undergo cranial surgery. This analysis was conducted between January 2, 2020, and August 8, 2023. Participants who underwent EC surgery during the index admission were compared with participants with no surgery in groups with a peripheral orthopedic injury or a TBI and were classified as having uncomplicated mild TBI (GCS score of 13-15 and negative CT results [CT- mTBI]), complicated mild TBI (GCS score of 13-15 and positive CT results [CT+ mTBI]), or moderate to severe TBI (GCS score of 3-12 [m/sTBI]). The primary outcomes were functional limitations quantified by the Glasgow Outcome Scale-Extended for all injuries (GOSE-ALL) and brain injury (GOSE-TBI) and neurocognitive outcomes at 2 weeks and 6 months after injury. A total of 1835 participants (mean [SD] age, 42.2 [17.8] years; 1279 [70%] male; 299 Black, 1412 White, and 96 other) were analyzed, including 1349 nonsurgical participants and 486 participants undergoing EC surgery. The participants undergoing EC surgery across all TBI severities had significantly worse GOSE-ALL scores at 2 weeks and 6 months compared with their nonsurgical counterparts. At 6 months after injury, m/sTBI and CT+ mTBI participants who underwent EC surgery had significantly worse GOSE-TBI scores (B = -1.11 [95% CI, -1.53 to -0.68] in participants with m/sTBI and -0.39 [95% CI, -0.77 to -0.01] in participants with CT+ mTBI) and performed worse on the Trail Making Test Part B (B = 30.1 [95% CI, 11.9-48.2] in participants with m/sTBI and 26.3 [95% CI, 11.3-41.2] in participants with CT+ mTBI). This study found that exposure to EC surgery and anesthesia was associated with adverse functional outcomes and impaired executive function after TBI. This unfavorable association warrants further investigation of the potential mechanisms and clinical implications that could inform decisions regarding the timing of surgical interventions in patients after TBI.

Classification of patients with dementia in a late life depression cohort using structural MRI

AbstractBackgroundLate life depression (LLD) is a risk factor for cognitive impairment, with up to 40% of depressed older adults showing persistent cognitive deficits even after symptom remission. Over 20% of Alzheimer’s disease patients exhibit depression‐like symptoms which can represent an early marker of disease (Tsuno et Homma., 2009). We hypothesized that automated classification algorithms trained on structural MRI could predict adjudicated diagnosis of cognitive impairment (CI) in this cohort.MethodOur study evaluated 295 patients with LLD. An adjudication committee consisting of two board‐certified psychiatrists and a clinical neuropsychologist determined ground‐truth labels for patient diagnostic results of CI (N = 145) or No CI (N = 150). Patients underwent T1‐weighted scans, which were segmented with Freesurfer 6.0.1 (freesurfer.net) packaged with fMRIPrep 1.5.8 (fmriprep.org) using the Desikan‐Killiany atlas. Cortical thickness and volumetric data were obtained along with demographic parameters. Freesurfer data was then regressed against estimated total intracranial volume. 11 classifications algorithms implemented in R were trained and tested on 209 and 88 patients, respectively, to classify if a patient has CI. All continuous‐valued data were normalized with respect to the training set mean and standard deviation.ResultTable 1 shows results from multiple classifications algorithms, including high sensitivity, specificity, and accuracy from adaptive boosting algorithms. The latter algorithms iteratively optimize a set of binary classification tree algorithms (Freund et Schapire., 1996).ConclusionVolumetric structural MRI biomarkers trained with machine learning classifiers can adequately categorize depressed older adults with CI which could assist the adjudication process. Future work incorporating structural MRI biomarkers with gold standard clinical data may improve earlier detection of cognitive impairment stemming from a neurodegenerative etiology.

Crosstalk between GABAA receptors in astrocytes and neurons triggered by general anesthetic drugs

General anesthetic drugs cause cognitive deficits that persist after the drugs have been eliminated. Astrocytes may contribute to such cognition-impairing effects through the release of one or more paracrine factors that increase a tonic inhibitory conductance generated by extrasynaptic γ-aminobutyric acid type A (GABAA) receptors in hippocampal neurons. The mechanisms underlying this astrocyte-to-neuron crosstalk remain unknown. Interestingly, astrocytes express anesthetic-sensitive GABAA receptors. Here, we tested the hypothesis that anesthetic drugs activate astrocytic GABAA receptors to initiate crosstalk leading to a persistent increase in extrasynaptic GABAA receptor function in neurons. We also investigated the signaling pathways in neurons and aimed to identify the paracrine factors released from astrocytes. Astrocytes and neurons from mice were grown in primary cell cultures and studied using in vitro electrophysiological and biochemical assays. We discovered that the commonly used anesthetics etomidate (injectable) and sevoflurane (inhaled) stimulated astrocytic GABAA receptors, which in turn promoted the release paracrine factors, that increased the tonic current in neurons via a p38 MAPK-dependent signaling pathway. The increase in tonic current was mimicked by exogenous IL-1β and abolished by blocking IL-1 receptors; however, unexpectedly, IL-1β and other cytokines were not detected in astrocyte-conditioned media. In summary, we have identified a novel form of crosstalk between GABAA receptors in astrocytes and neurons that engages a p38 MAPK-dependent pathway.Brief commentary BackgroundMany older patients experience cognitive deficits after surgery. Anesthetic drugs may be a contributing factor as they cause a sustained increase in the function of “memory blocking” extrasynaptic GABAA receptors in neurons. Interestingly, astrocytes are required for this increase; however, the mechanisms underlying the astrocyte-to-neuron crosstalk remain unknown. Translational significanceWe discovered that commonly used general anesthetic drugs stimulate GABAA receptors in astrocytes, which in turn release paracrine factors that trigger a persistent increase in extrasynaptic GABAA receptor function in neurons via p38 MAPK. This novel form of crosstalk may contribute to persistent cognitive deficits after general anesthesia and surgery.

Prediction of cognitive outcome after mild traumatic brain injury from acute measures of communication within brain networks

A considerable but ill-defined proportion of patients with mild traumatic brain injury (mTBI) experience persistent cognitive sequelae; the ability to identify such individuals early can help their neurorehabilitation. Here we tested the hypothesis that acute measures of efficient communication within brain networks are associated with patients’ risk for unfavorable cognitive outcome six months after mTBI. Diffusion and T1-weighted magnetic resonance imaging, alongside cognitive measures, were obtained to map connectomes both one week and six months post injury in 113 adult patients with mTBI (71 males). For task-related brain networks, communication measures (characteristic path length, global efficiency, navigation efficiency) were moderately correlated with changes in cognition. Taking into account the covariance of age and sex, more unfavorable communication within networks were associated with worse outcomes within cognitive domains frequently impacted by mTBI (episodic and working memory, verbal fluency, inductive reasoning, and processing speed). Individuals with more unfavorable outcomes had significantly longer and less efficient pathways within networks supporting verbal fluency (all t > 2.786, p < .006), highlighting the vulnerability of language to mTBI. Participants in whom a task-related network was relatively inefficient one week post injury were up to eight times more likely to have unfavorable cognitive outcome pertaining to that task. Our findings suggest that communication measures within task-related networks identify mTBI patients who are unlikely to develop persistent cognitive deficits after mTBI. Our approach and findings can help to stratify mTBI patients according to their expected need for follow-up and/or neurorehabilitation.

IC3 protocol: a longitudinal observational study of cognition after stroke using novel digital health technology

IntroductionStroke is a major cause of death and disability worldwide, frequently resulting in persistent cognitive deficits among survivors. These deficits negatively impact recovery and therapy engagement, and their treatment is...

44 A Case Study of Non-Alcoholic Wernicke’s Encephalopathy in a Young Man with Intractable Vomiting

Objective:Wernicke’s encephalopathy (WE) is an acute neurological condition caused by thiamine deficiency. The typical presentation is characterized by a triad of oculomotor abnormalities, gait ataxia, and altered mental status, though patients rarely present with all three symptoms. WE is a serious medical condition that is associated with high rates of morbidity and mortality if left untreated. It is most commonly seen in patients with severe alcohol use disorder; however, it has also been found in patients with thiamine deficiency due to other causes of malnutrition such as prolonged starvation, hyperemesis, dialysis, cancer, and geriatric surgery. Despite growing research demonstrating WE in non-alcoholic populations, it is frequently misdiagnosed in patients without an extensive alcohol-use history, particularly when they do not present with the typical clinical triad of symptoms. Thus, more knowledge about non-alcoholic WE is needed to improve diagnostic accuracy.Participants and Methods:We present a case of a 26-year-old male with an unremarkable alcohol use history, who was diagnosed with WE following a 6-week period of excessive nausea and vomiting of unclear etiology. He presented to the ED three times prior to his diagnosis, and was treated with intravenous hydration, Zofran, and Pepcid. He presented to the ED for the fourth time with altered mental status and gait ataxia and was diagnosed with WE based on MRI findings. He was admitted and treated with high doses of IV thiamine and folate. His clinical course was tracked over time via outpatient neurology examinations, and his cognitive functioning was assessed with an outpatient neuropsychological evaluation approximately six months post-discharge. Record review, including clinical notes, lab tests, and imaging results supplement his outpatient neuropsychological evaluation performance.Results:Data from a comprehensive outpatient neuropsychological evaluation approximately six months after WE diagnosis is presented. His cognitive profile was characterized by impaired performance on measures of verbal fluency and memory, including encoding and retention of verbal and visual information (with minimal benefit from cueing). Given these impairments and continued functional declines related to cognitive deficits, he met criteria for a Major Neurocognitive Disorder. These results demonstrate persistent cognitive deficits beyond the acute WE period.Conclusions:WE is a serious neurological condition that can have lasting cognitive effects if left untreated. This case demonstrates persistent cognitive impairments six months after WE diagnosis in a young patient with an unremarkable alcohol history. These findings highlight the necessity of increased diagnostic efficiency of WE in non-alcoholic patients, as immediate thiamine treatment is essential to the recovery process. Neuropsychological functioning at a longer interval will be useful in further elucidating cognitive prognosis as well as providing quality of life recommendations.

Using Cognitive-Motor Dual-Tasks and Functional Near-Infrared Spectroscopy to Characterize Older Adults with and without Subjective Cognitive Decline.

Subjective cognitive decline (SCD) refers to individuals who report persistent cognitive deficits but perform normally on neuropsychological tests. Performance may be facilitated by increased prefrontal cortex activation, known as neural compensation, and could be used to differentiate between older adults with and without SCD. This cross-sectional pilot study measured changes in the hemodynamic response (ΔHbO2) using functional near-infrared spectroscopy (fNIRS) as well as cognitive and motor performance during fine and gross motor dual-tasks in older adults with and without SCD. Twenty older adults over 60 years old with (n = 10) and without (n = 10) SCD were recruited. Two experiments were conducted using 1) gross motor walking and 2) fine motor finger tapping tasks that were paired with an n-back working memory task. Participants also completed neuropsychological assessments and questionnaires on everyday functioning. Repeated measures ANOVAs demonstrated slower response times during dual-task gait compared to the single task (p = 0.032) and in the non-SCD group, slower gait speed was also observed in the dual compared to single task (p = 0.044). Response times during dual-task finger tapping were slower than the single task (p = 0.049) and greater ΔHbO2 was observed overall in the SCD compared to non-SCD group (p = 0.002). Examining neural and performance outcomes revealed differences between SCD and non-SCD groups and single and dual-tasks. Greater brain activation during dual-task finger tapping may reflect neural compensation, which should be examined in a larger sample and longitudinally to better characterize SCD.

A - 114 Long Term Cognitive Sequela of Intracranial Radiation Therapy in a Pediatric Cerebellar Medulloblastoma Survivor.

Intracranial radiation therapy (IRT) for pediatric brain tumors is associated with late delayed brain injury due to cerebrovascular abnormality, white matter necrosis, demyelination, and gliosis which are irreversible. As a result, persistent cognitive deficits in adulthood emerge which are aggravated by younger age at diagnosis, higher radiation dose, whole brain radiation (WBR), and concurrent chemotherapy. The case is a childhood brain tumor survivor seen 18years post treatment who displayed cognitive deficits reflecting the cognitive sequela of WBR that overlapped with the anatomical distribution of white matter damage sustained. 23-year-old Black male with a history of childhood cerebellar medulloblastoma diagnosed at age 4, tumor resection, WBR, chemotherapy, more recent seizure disorder and medullary stroke, diabetes, and hypertension was seen for a neuropsychological evaluation due to memory complaints. His neuroimaging showed white matter hyperintensities in bilateral temporal and occipital lobes, bilateral cerebellar hemispheres, bilateral frontal lobes, medial posterior right cerebellar cyst, and 10 x 5mm cyst in the left temporal lobe. Results showed FSIQ = 59 and deficits in language, processing speed, visuospatial abilities, executive functioning, and verbal memory. His auditory working memory and visual memory were preserved. Based on his numerous adaptive limitations, moderate intellectual development disorder diagnosis was given. Deficits across several cognitive domains were consistent with multi-focal white matter lesions seen in patient's neuroimaging which reflect radiographic findings related to long-term sequela of previous intracranial radiation. A unique finding was relatively preserved visual memory as findings related to asymmetrical memory dysfunction in childhood medulloblastoma survivors are scarce.

Disrupted functional connectivity of the striatum in patients with diffuse axonal injury: a resting-state functional MRI study.

Diffuse axonal injury (DAI) disrupts the integrity of white matter microstructure and affects brain functional connectivity, resulting in persistent cognitive, behavioral and affective deficits. Mounting evidence suggests that altered cortical-subcortical connectivity is a major contributor to cognitive dysfunction. The functional integrity of the striatum is particularly vulnerable to DAI, but has received less attention. This study aimed to investigate the alteration patterns of striatal subdivision functional connectivity. Twenty-six patients with DAI and 27 healthy controls underwent resting-state fMRI scans on a 3.0 T scanner. We assessed striatal subdivision functional connectivity using a seed-based analysis in DAI. Furthermore, a partial correlation was used to measure its clinical association. Compared to controls, patients with DAI showed decreased functional connectivity between the right inferior ventral striatum and right inferior frontal gyrus, as well as the right inferior parietal lobule, between the left inferior ventral striatum and right inferior frontal gyrus, between the right superior ventral striatum and bilateral cerebellar posterior lobe, between the bilateral dorsal caudal putamen and right anterior cingulate gyrus, and between the right dorsal caudal putamen and right inferior parietal lobule. Moreover, decreased functional connectivity was observed between the left dorsal caudate and the right cerebellar posterior lobe, while increased functional connectivity was found between the left dorsal caudate and right inferior parietal lobule. Correlation analyses showed that regions with functional connectivity differences in the DAI group correlated with multiple clinical scoring scales, including cognition, motor function, agitated behavior, and anxiety disorders. These findings suggest that abnormalities in cortico-striatal and cerebellar-striatal functional connectivity are observed in patients with DAI, enriching our understanding of the neuropathological mechanisms of post-injury cognitive disorders and providing potential neuroimaging markers for the diagnosis and treatment of DAI.

Neuropsychological deficits in patients with persistent COVID-19 symptoms: a systematic review and meta-analysis

Long-term persistent symptoms of COVID-19 affect 30–80% of patients who have recovered from the disease and may continue for a long time after the disease has been overcome. The duration of these symptoms over time might have consequences that affect different aspects of health, such as cognitive abilities. The main objective of this systematic review and meta-analysis was to objectify the persistent COVID-19 cognitive deficits after acute phase of infection and to summarize the existing evidence. Additionally, we aimed to provide a comprehensive overview to further understand and address the consequences of this disease. Our protocol was registered in PROSPERO (CRD42021260286). Systematic research was conducted in the Web of Science, MEDLINE, PubMed, PsycINFO, Scopus, and Google Scholar databases from January 2020 to September 2021. Twenty-five studies were included, six of which were analyzed for the meta-analysis, and consisted of 175 patients who had recovered from COVID-19 and 275 healthy individuals. Analyses of cognitive performance of post-COVID-19 patients and healthy volunteers were compared using a random-effects model. The results showed an overall medium–high effect size (g = −.68, p = .02) with a 95% CI (−1.05 to −.31), with a significantly moderate level of heterogeneity among studies (Z = 3.58, p < .001; I2 = 63%). The results showed that individuals who had recovered from COVID-19 showed significant cognitive deficits compared to controls. Future studies should carefully assess the long-term progression of cognitive impairments in patients with persistent COVID-19 symptoms, as well as the effectiveness of rehabilitation interventions. Nevertheless, there is an urgent need to know the profile to speed up development of prevention plans as well as specific interventions. Since more information is being obtained and more studies are being conducted on the subject, the need to examine this symptomatology multidisciplinary to achieve greater scientific evidence of its incidence and prevalence has become increasingly clear.

Relationship between cognitive ability and emotional problems in the context of poverty: a Nigerian adolescent twin study.

Although previous studies have identified negative relationships between cognitive ability and emotional problems (EP), mechanism explaining these relationships remained unclear. This study evaluated two explanatory models using bivariate moderation model-fitting analysis in a twin design. The resilience model suggests that high cognitive ability decreases the risk of EP in adverse settings, and the scarring model suggests that EP symptoms lead to persistent cognitive deficits following onset. The Standard Progressive Matrices Plus (SPM) and EP scale were administered to a sample of 3,202 twins (mean age = 14.62 ± 1.74years) attending public schools in Nigeria. The results of bivariate moderation model-fitting analyses only supported the resilience model. Moderation effects were not significant in the scarring model when genetic and environmental influences were incorporated. The best-fitting bivariate moderation model assuming the resilience model yielded a genetic correlation of - 0.57 (95% CI = -0.40, - 0.84) with no significant environmental correlations. Moreover, the SPM moderated the environmental, not genetic, influences on EP, such that environmental influences were strong when protective factors were absent (low SPM) and weak when these were present (high SPM). These results indicate the need to develop targeted prevention and intervention strategies for EP in adolescents displaying low cognitive ability in deprived settings.

DNA Methylation-Mediated Mfn2 Gene Regulation in the Brain: A Role in Brain Trauma-Induced Mitochondrial Dysfunction and Memory Deficits.

Repeated mild traumatic brain injuries (rMTBI) affect mitochondrial homeostasis in the brain. However, mechanisms of long-lasting neurobehavioral effects of rMTBI are largely unknown. Mitofusin 2 (Mfn2) is a critical component of tethering complexes in mitochondria-associated membranes (MAMs) and thereby plays a pivotal role in mitochondrial functions. Herein, we investigated the implications of DNA methylation in the Mfn2 gene regulation, and its consequences on mitochondrial dysfunction in the hippocampus after rMTBI. rMTBI dramatically reduced the mitochondrial mass, which was concomitant with decrease in Mfn2 mRNA and protein levels. DNA hypermethylation at the Mfn2 gene promoter was observed post 30days of rMTBI. The treatment of 5-Azacytidine, a pan DNA methyltransferase inhibitor, normalized DNA methylation levels at Mfn2 promoter, which further resulted into restoration of Mfn2 function. The normalization of Mfn2 function was well correlated with recovery in memory deficits in rMTBI-exposed rats. Since, glutamate excitotoxicity serves as a primary insult after TBI, we employed in vitro model of glutamate excitotoxicity in human neuronal cell line SH-SY5Y to investigate the causal epigenetic mechanisms of Mfn2 gene regulation. The glutamate excitotoxicity reduced Mfn2 levels via DNA hypermethylation at Mfn2 promoter. Loss of Mfn2 caused significant surge in cellular and mitochondrial ROS levels with lowered mitochondrial membrane potential in cultured SH-SY5Y cells. Like rMTBI, these consequences of glutamate excitotoxicity were also prevented by 5-AzaC pre-treatment. Therefore, DNA methylation serves as a vital epigenetic mechanism involved in Mfn2 expression in the brain; and this Mfn2 gene regulation may play a pivotal role in rMTBI-induced persistent cognitive deficits. Closed head weight drop injury method was employed to induce repeated mild traumatic brain (rMTBI) in jury in adult, male Wistar rats. rMTBI causes hyper DNA methylation at the Mfn2 promoter and lowers the Mfn2 expression triggering mitochondrial dysfunction. However, the treatment of 5-azacytidine normalizes DNA methylation at the Mfn2 promoter and restores mitochondrial function.

Associations between aberrant working memory-related neural activity and cognitive impairments in somatically healthy, remitted patients with mood disorders.

Persistent cognitive deficits are prevalent in patients with bipolar disorder (BD) and unipolar disorder (UD), but treatments effectively targeting cognition in these mood disorders are lacking. This is partly due to poor insight into the neuronal underpinnings of cognitive deficits. The aim of this functional magnetic resonance imaging (fMRI) study was to investigate the neuronal underpinnings of working memory (WM)-related deficits in somatically healthy, remitted patients with BD or UD (n = 66) with cognitive and functional impairments compared to 38 healthy controls (HC). The participants underwent neuropsychological testing and fMRI, while performing a visuospatial and a verbal N-back WM paradigm. Relative to HC, patients exhibited hypo-activity across dorsolateral prefrontal cortex as well as frontal and parietal nodes of the cognitive control network (CCN) and hyper-activity in left orbitofrontal cortex within the default mode network (DMN) during both visuospatial and verbal WM performance. Verbal WM-related response in the left posterior superior frontal gyrus (SFG) within CCN was lower in patients and correlated positively with out-of-scanner executive function performance across all participants. Our findings suggest that cognitive impairments across BD and UD are associated with insufficient recruitment of task-relevant regions in the CCN and down-regulation of task-irrelevant orbitofrontal activity within the DMN during task performance. Specifically, a lower recruitment of the left posterior SFG within CCN during verbal WM was associated with lower cognitive performance.

Tobacco and mental health- Deciphering the vulnerability to nicotine in patients with schizophrenia as a function of their dopamine neurotransmission genes: a clinical and preclinical study

IntroductionSchizophrenia (SZ) is a severe and frequent mental disorder that has multifactorial origins (genetic but also environmental vulnerability, gene environment interactions). Our team has shown that in France smoking is common among these patients and often begins before the onset of symptoms. This calls into question the hypothesis of self-medication of psychotic symptoms and cognitive disorders by tobacco consumption, and raises the question of specific interactions between nicotine consumption and the genes of the dopaminergic and cholinergic nicotinic systems, in particular with regard to adolescence, period of neurodevelopmental vulnerability.Objectivesto study (i) the interactions between the DA system and exogenous nicotine in a pre-clinical mouse model (transgenic for DAT) (ii) the impact of smoking on the psychotic and clinical phenotype in a national cohort of SZ patients (iii) interactions between tobacco consumption and several genetic polymorphisms of the dopaminergic and nicotinic system in SZ population. Hypothesis: Disruption of the balance between DA and nicotine systems by nicotine consumption in adolescence may be a key neurobiological mechanism for the emergence of SZ disorders.MethodsThe characterization of the model is behavioral (anxiety, memory, social interactions, locomotion, motor coordination) but also biochemical. For the clinical approach, we exploit the clinical / cognitive / genetic data of a national cohort (Fondamental foundation) and another smaller and local cohort.ResultsWe demonstrate, for the clinical study, that some clinical and cognitive characteristics are associated with tobacco use in schizophrenia patients, with more cognitive distubrances in smokers, against the self medication hypothesis. Genes envionment interactions also demonstrate associations with genes involved in dopaminergic system. Regarding the preclinical study, we show a gene environment interaction, as heterozygote mice for the DAT gene exposed to Nicotine durig a critical neurodevelopmental window ( adolescence) show a loss of familiarity in the social memory test and a loss of cognitive flexibility at the set shifting test, similar to what is found in schizophrenia.ConclusionsTBetter characterization of patients with schizophrenia is necessary to better understand the physiopathology of this disease and explore new personalized preventive and therapeutical targets. We show that tobacco is associated with cognitive disturbances in schizophrenia patients, against selfmedication hypothesis; and in our animal model, that nicotine exposition during the adolescence combined to a moderate cortical and limbic hyperdopaminergia, is associated with persistent cognitive and social deficits, in favor of a gene environment interaction.Disclosure of InterestNone Declared

DEMENCIA COM CORPOS DE LEWY EM PERICIA PREVIDENCIARIA

Dementia is a clinical syndrome characterized by multiple, acquired and persistent cognitive deficits, capable of substantially interfering in the patient’s activities of daily living. The diagnosis of Dementia with Lewy Bodies (LBD) is characterized by fluctuation in cognitive functions, recurrent, well-formed, and detailed visual hallucinations, and parkinsonism, with stiffness, tremor, bradykinesia, and slurred speech. Our goal is to describe a case report of LBD that for several years was diagnosed and treated as depression. It is extremely important to have detailed medical research in these cases, including performing differential diagnosis with depression, in order to enable adequate treatment, family guidance and receipt of financial benefits provided by government authorities.

Examination of the Presence of COVID-19 Encephalopathy on Inpatient Acute Rehabilitation Outcomes and Disability

<h3>Research Objectives</h3> The objective of the current study was to investigate the impact of COVID-19 encephalopathy on acute inpatient rehabilitation outcome. <h3>Design</h3> This retrospective study assessed functional ability pre-intervention (admission) and post-intervention (discharge) among COVID-19 patients who received acute inpatient rehabilitation between April 2020 and March 2021. <h3>Setting</h3> Participants received care in a dedicated COVID unit at a freestanding acute inpatient rehabilitation facility. <h3>Participants</h3> 161 inpatients were divided into two groups according to COVID-encephalopathy status: 87 negative (CE-) and 74 positive (CE+). Encephalopathy status was determined based on Chart-Based Delirium Identification Instrument using electronic medical records. The sample was 61% male / 39% female, 62% White, 14% Black, 8% Hispanic, 4% Asian, 12% Other/declined. Mean age was 62 (SD=15.2) and mean education was 13 years (SD=3.9). <h3>Interventions</h3> Rehabilitation interventions utilized a medically-based, multidisciplinary approach. All participants received a minimum of three hours of physical, occupational and/or speech therapy five days / week during inpatient stay. <h3>Main Outcome Measures</h3> The total raw score from the self-care and mobility section of the Inpatient Rehabilitation Facility Patient Assessment Instrument (IRF-PAI) was used to assess overall functional ability at admission and discharge. The Brief Interview for Mental Status was utilized to assess orientation. <h3>Results</h3> At admission, encephalopathy groups did not differ in overall ability. In contrast, at discharge overall ability was significantly higher with encephalopathy and IRF-PAI change per day trended higher with encephalopathy. Finally, at discharge orientation was associated with overall ability in the CE+ group. <h3>Conclusions</h3> Following inpatient rehabilitation CE+ patients had less overall disability than CE- patients but residual problems with cognitive functioning were associated with severe overall disability in the CE+ group. Findings highlight the complexity of COVID-19 symptom manifestation and persistent physical and cognitive deficits during the course of a COVID-19 infection and recovery. <h3>Author(s) Disclosures</h3> The authors have no conflicts of interest to declare nor any financial or non-financial interests to disclose.