Cognitive reserve, depressive symptoms, obesity, and change in employment status predict mental processing speed and executive function after COVID-19.

The risk factors for post-COVID-19 cognitive impairment have been poorly described. This study aimed to identify the sociodemographic, clinical, and lifestyle characteristics that characterize a group of post-COVID-19 condition (PCC) participants with neuropsychological impairment. The study sample included 426 participants with PCC who underwent a neurobehavioral evaluation. We selected seven mental speed processing and executive function variables to obtain a data-driven partition. Clustering algorithms were applied, including K-means, bisecting K-means, and Gaussian mixture models. Different machine learning algorithms were then used to obtain a classifier able to separate the two clusters according to the demographic, clinical, emotional, and lifestyle variables, including logistic regression with least absolute shrinkage and selection operator (LASSO) (L1) and Ridge (L2) regularization, support vector machines (linear/quadratic/radial basis function kernels), and decision tree ensembles (random forest/gradient boosting trees). All clustering quality measures were in agreement in detecting only two clusters in the data based solely on cognitive performance. A model with four variables (cognitive reserve, depressive symptoms, obesity, and change in work situation) obtained with logistic regression with LASSO regularization was able to classify between good and poor cognitive performers with an accuracy and a weighted averaged precision of 72%, a recall of 73%, and an area under the curve of 0.72. PCC individuals with a lower cognitive reserve, more depressive symptoms, obesity, and a change in employment status were at greater risk for poor performance on tasks requiring mental processing speed and executive function. Study registration: www.ClinicalTrials.gov , identifier NCT05307575.

Cognitive and emotional predictors of quality of life and functioning after COVID-19.

OBJECTIVE: A long-term decline in health-related quality of life (HRQoL) has been reported after coronavirus disease 2019 (COVID-19). Studies with people with persistent symptoms showed inconsistent outcomes. Cognition and emotion are important determinants in HRQoL, but few studies have examined their prognostic significance for HRQoL and functionality in post-COVID patients with persisting symptoms. We aimed to describe QoL, HRQoL, and functioning in individuals post-COVID with varying COVID-19 severities and to investigate the predictive value of cognitive and emotional variables for QoL, HRQoL, and functioning. METHODS: In total, 492 participants (398 post-COVID and 124 healthy controls) underwent a neurobehavioral examination that included assessments of cognition, mood, QoL/HRQoL (WHOQOL-BREF, EQ-5D), and functioning (WHODAS-II). Analysis of covariance and linear regression models were used to study intergroup differences and the relationship between cognitive and emotional variables and QoL and functioning. RESULTS: The Physical and Psychological dimensions of WHOQoL, EQ-5D, and WHODAS Cognition, Mobility, Life Activities, and Participation dimensions were significantly lower in post-COVID groups compared with a control group. Regression models explaining 23.9%-53.9% of variance were obtained for the WHOQoL-BREF dimensions and EQ-5D, with depressive symptoms, post-COVID symptoms, employment status, income, and mental speed processing as main predictors. For the WHODAS, models explaining 17%-60.2% of the variance were obtained. Fatigue, depressive symptoms, mental speed processing, and post-COVID symptoms were the main predictors. INTERPRETATION: QoL/HRQoL and functioning after COVID-19 in individuals with persistent symptoms were lower than in non-affected persons. Depressive symptoms, fatigue, and slower mental processing speed were predictors of lower QoL/HRQoL and functioning.

Eye movements in patients with post-COVID condition.

Eye movement control is impaired in some neurological conditions, but the impact of COVID-19 on eye movements remains unknown. This study aims to investigate differences in oculomotor function and pupil response in individuals who suffer post-COVID-19 condition (PCC) with cognitive deficits. Saccades, smooth pursuit, fixation, vergence and pupillary response were recorded using an eye tracker. Eye movements and pupil response parameters were computed. Data from 16 controls, 38 COVID mild (home recovery) and 19 COVID severe (hospital admission) participants were analyzed. Saccadic latencies were shorter in controls (183 ± 54 ms) than in COVID mild (236 ± 83 ms) and COVID severe (227 ± 42 ms) participants (p = 0.017). Fixation stability was poorer in COVID mild participants (Bivariate Contour Ellipse Area of 0.80 ± 1.61°2 vs 0.36 ± 0.65 °2 for controls, p = 0.019), while percentage of pupil area reduction/enlargement was reduced in COVID severe participants (39.7 ± 12.7%/31.6 ± 12.7% compared to 51.7 ± 22.0%/49.1 ± 20.7% in controls, p < 0.015). The characteristics of oculomotor alterations found in PCC may be useful to understand different pathophysiologic mechanisms.

COVID-19 severity is related to poor executive function in people with post-COVID conditions.

Patients with post-coronavirus disease 2019 (COVID-19) conditions typically experience cognitive problems. Some studies have linked COVID-19 severity with long-term cognitive damage, while others did not observe such associations. This discrepancy can be attributed to methodological and sample variations. We aimed to clarify the relationship between COVID-19 severity and long-term cognitive outcomes and determine whether the initial symptomatology can predict long-term cognitive problems. Cognitive evaluations were performed on 109 healthy controls and 319 post-COVID individuals categorized into three groups according to the WHO clinical progression scale: severe-critical (n = 77), moderate-hospitalized (n = 73), and outpatients (n = 169). Principal component analysis was used to identify factors associated with symptoms in the acute-phase and cognitive domains. Analyses of variance and regression linear models were used to study intergroup differences and the relationship between initial symptomatology and long-term cognitive problems. The severe-critical group performed significantly worse than the control group in general cognition (Montreal Cognitive Assessment), executive function (Digit symbol, Trail Making Test B, phonetic fluency), and social cognition (Reading the Mind in the Eyes test). Five components of symptoms emerged from the principal component analysis: the "Neurologic/Pain/Dermatologic" "Digestive/Headache", "Respiratory/Fever/Fatigue/Psychiatric" and "Smell/ Taste" components were predictors of Montreal Cognitive Assessment scores; the "Neurologic/Pain/Dermatologic" component predicted attention and working memory; the "Neurologic/Pain/Dermatologic" and "Respiratory/Fever/Fatigue/Psychiatric" components predicted verbal memory, and the "Respiratory/Fever/Fatigue/Psychiatric," "Neurologic/Pain/Dermatologic," and "Digestive/Headache" components predicted executive function. Patients with severe COVID-19 exhibited persistent deficits in executive function. Several initial symptoms were predictors of long-term sequelae, indicating the role of systemic inflammation and neuroinflammation in the acute-phase symptoms of COVID-19." Study Registration: www.ClinicalTrials.gov , identifier NCT05307549 and NCT05307575.

Neuropsychological impairment in post-COVID condition individuals with and without cognitive complaints.

One of the most prevalent symptoms of post-COVID condition is cognitive impairment, which results in a significant degree of disability and low quality of life. In studies with large sample sizes, attention, memory, and executive function were reported as long-term cognitive symptoms. This study aims to describe cognitive dysfunction in large post-COVID condition individuals, compare objective neuropsychological performance in those post-COVID condition individuals with and without cognitive complaints, and identify short cognitive exams that can differentiate individuals with post-COVID symptoms from controls. To address these aims, the Nautilus project was started in June 2021. During the first year, we collected 428 participants' data, including 319 post-COVID and 109 healthy controls (18-65 years old) from those who underwent a comprehensive neuropsychological battery for cognitive assessment. Scores on tests assessing global cognition, learning and long-term memory, processing speed, language and executive functions were significantly worse in the post-COVID condition group than in healthy controls. Montreal Cognitive Assessment, digit symbol test, and phonetic verbal fluency were significant in the binomial logistic regression model and could effectively distinguish patients from controls with good overall sensitivity and accuracy. Neuropsychological test results did not differ between those with and without cognitive complaints. Our research suggests that patients with post-COVID conditions experience significant cognitive impairment and that routine tests like the Montreal Cognitive Assessment, digit symbol, and phonetic verbal fluency test might identify cognitive impairment. Thus, the administration of these tests would be helpful for all patients with post-COVID-19 symptoms, regardless of whether cognitive complaints are present or absent. Study registration: www.ClinicalTrials.gov, identifiers NCT05307549 and NCT05307575.

Effects and mechanisms of mindfulness training and physical exercise on cognition, emotional wellbeing, and brain outcomes in chronic stroke patients: Study protocol of the MindFit project randomized controlled trial.

Background: Post-stroke cognitive and emotional complications are frequent in the chronic stages of stroke and have important implications for the functionality and quality of life of those affected and their caregivers. Strategies such as mindfulness meditation, physical exercise (PE), or computerized cognitive training (CCT) may benefit stroke patients by impacting neuroplasticity and brain health. Materials and methods: One hundred and forty-one chronic stroke patients are randomly allocated to receive mindfulness-based stress reduction + CCT (n = 47), multicomponent PE program + CCT (n = 47), or CCT alone (n = 47). Interventions consist of 12-week home-based programs five days per week. Before and after the interventions, we collect data from cognitive, psychological, and physical tests, blood and stool samples, and structural and functional brain scans. Results: The effects of the interventions on cognitive and emotional outcomes will be described in intention-to-treat and per-protocol analyses. We will also explore potential mediators and moderators, such as genetic, molecular, brain, demographic, and clinical factors in our per-protocol sample. Discussion: The MindFit Project is a randomized clinical trial that aims to assess the impact of mindfulness and PE combined with CCT on chronic stroke patients' cognitive and emotional wellbeing. Furthermore, our design takes a multimodal biopsychosocial approach that will generate new knowledge at multiple levels of evidence, from molecular bases to behavioral changes. Clinical trial registration: www.ClinicalTrials.gov, identifier NCT04759950.

The interaction effect between BDNF val66met polymorphism and obesity on executive functions and frontal structure.

The prevalence of obesity is increasing worldwide. Previous research has shown a relationship between obesity and both executive functioning alterations and frontal cortex volume reductions. The Brain Derived Neurotrophic Factor val66met polymorphism, involved in eating behavior, has also been associated with executive functions and prefrontal cortex volume, but to date it has not been studied in relation to obesity. Our aim is to elucidate whether the interaction between the Brain Derived Neurotrophic Factor val66met polymorphism and obesity status influences executive performance and frontal-subcortical brain structure. Sixty-one volunteers, 34 obese and 27 controls, age range 12-40, participated in the study. Participants were assigned to one of two genotype groups (met allele carriers, n = 16, or non-carriers, n = 45). Neuropsychological assessment comprised the Trail Making Test, the Stroop Test and the Wisconsin Card Sorting Test, all tasks that require response inhibition and cognitive flexibility. Subjects underwent magnetic resonance imaging in a Siemens TIM TRIO 3T scanner and images were analyzed using the FreeSurfer software. Analyses of covariance controlling for age and intelligence showed an effect of the obesity-by-genotype interaction on perseverative responses on the Wisconsin Card Sorting Test as well as on precentral and caudal middle frontal cortical thickness: obese met allele carriers showed more perseverations on the Wisconsin Card Sorting Test and lower frontal thickness than obese non-carriers and controls. In conclusion, the Brain Derived Neurotrophic Factor may play an important role in executive functioning and frontal brain structure in obesity.

Does verbal and gestural expression ability predict comprehension ability in cerebral palsy?

Some people with cerebral palsy have motor and associated impairments that may hinder verbal and gestural expression to various extents. This study explores whether the ability to produce verbal or gestural expressions may be related to the comprehension of verbal communications and gestures. The influence of severity of motor impairment, general cognitive performance, and age on comprehension ability was also explored. Forty people with cerebral palsy were assigned to different groups according to their verbal and gestural expression abilities. A neuropsychological assessment of comprehension abilities and general cognitive performance was carried out. Multiple linear regression analysis was applied to identify the possible influence of expression abilities on comprehension abilities and also to detect the possible contribution of severity of motor impairment, general cognitive performance, and age. Results indicate that verbal and gestural comprehension was mainly predicted by general cognitive performance. Severity of motor impairment and age did not contribute to predicting comprehension abilities. Only verbal grammar comprehension was significantly predicted by verbal expression ability. Verbal expression ability may be an important marker for cerebral palsy therapies. In non-ambulant patients with bilateral cerebral palsy, impaired gestural expression should not be taken as an indicator of impaired gestural comprehension.

Frontal cortical thinning and subcortical volume reductions in early adulthood obesity.

Obesity depends on homeostatic and hedonic food intake behavior, mediated by brain plasticity changes in cortical and subcortical structures. The aim of this study was to investigate cortical thickness and subcortical volumes of regions related to food intake behavior in a healthy young adult sample with obesity. Thirty-seven volunteers, 19 with obesity (age=33.7±5.7 (20-39) years body-mass index (BMI)=36.08±5.92 (30.10-49.69)kg/m(2)) and 18 controls (age=32.3±5.9 (21-40) years; BMI=22.54±1.94 (19.53-24.97)kg/m(2)) participated in the study. Patients with neuropsychiatric or biomedical disorders were excluded. We used FreeSurfer software to analyze structural magnetic resonance images (MRI) and obtain global brain measures, cortical thickness and subcortical volume estimations. Finally, correlation analyses were performed for brain structure data and obesity measures. There were no between-group differences in age, gender, intelligence or education. Results showed cortical thickness reductions in obesity in the left superior frontal and right medial orbitofrontal cortex. In addition, the obesity group had lower ventral diencephalon and brainstem volumes than controls, while there were no differences in any other subcortical structure. There were no statistically significant correlations between brain structure and obesity measures. Overall, our work provides evidence of the structural brain characteristics associated with metabolically normal obesity. We found reductions in cortical thickness, ventral diencephalon and brainstem volumes in areas that have been implicated in food intake behavior.

Alterations of the salience network in obesity: a resting-state fMRI study.

Obesity is a major health problem in modern societies. It has been related to abnormal functional organization of brain networks believed to process homeostatic (internal) and/or salience (external) information. This study used resting-state functional magnetic resonance imaging analysis to delineate possible functional changes in brain networks related to obesity. A group of 18 healthy adult participants with obesity were compared with a group of 16 lean participants while performing a resting-state task, with the data being evaluated by independent component analysis. Participants also completed a neuropsychological assessment. Results showed that the functional connectivity strength of the putamen nucleus in the salience network was increased in the obese group. We speculate that this abnormal activation may contribute to overeating through an imbalance between autonomic processing and reward processing of food stimuli. A correlation was also observed in obesity between activation of the putamen nucleus in the salience network and mental slowness, which is consistent with the notion that basal ganglia circuits modulate rapid processing of information.

Dopamine genes (DRD2/ANKK1-TaqA1 and DRD4-7R) and executive function: their interaction with obesity.

Obesity is a multifactorial disease caused by the interaction between genotype and environment, and it is considered to be a type of addictive alteration. The A1 allele of the DRD2/ANKK1-TaqIA gene has been associated with addictive disorders, with obesity and with the performance in executive functions. The 7 repeat allele of the DRD4 gene has likewise been associated with the performance in executive functions, as well as with addictive behaviors and impulsivity. Participants were included in the obesity group (N = 42) if their body mass index (BMI) was equal to or above 30, and in the lean group (N = 42) if their BMI was below 25. The DRD2/ANKK1-TaqIA and DRD4 VNTR polymorphisms were obtained. All subjects underwent neuropsychological assessment. Eating behavior traits were evaluated. The 'DRD2/ANKK1-TaqIA A1-allele status' had a significant effect on almost all the executive variables, but no significant 'DRD4 7R-allele status' effects were observed for any of the executive variables analyzed. There was a significant 'group' x 'DRD2/ANKK1-TaqIA A1-allele status' interaction effect on LN and 'group' x 'DRD4 7R-allele status' interaction effect on TMT B-A score. Being obese and a carrier of the A1 allele of DRD2/ANKK1-TaqIA or the 7R allele of DRD4 VNTR polymorphisms could confer a weakness as regards the performance of executive functions.

Improvement of cognitive flexibility and cingulate blood flow correlates after atypical antipsychotic treatment in drug-naive patients with first-episode schizophrenia.

The aim of this study was to examine the changes in cognitive flexibility and associated cerebral blood flow in the anterior cingulate lobe of drug-naive patients with first-episode schizophrenia who were treated with atypical antipsychotics for 6 weeks. Single photon emission computed tomography (SPECT) images were obtained from 8 healthy subjects both at rest and while performing the flexibility subtest of the TAP (Test for Attentional Performance). SPECT images were obtained in parallel from 8 first-episode drug-naive schizophrenic patients while they were performing the same task both before and after 6 weeks of neuroleptic treatment. In the control group, an increase in the perfusion indices of the dorsal section of the anterior cingulate gyrus was observed in the activation condition. Task performance was altered and the level of perfusion of the brain region related to the task execution was significantly decreased in the patients at baseline. After treatment, there was a significant improvement in both task performance and the level of perfusion of the dorsal section of the anterior cingulate. We conclude that treatment with second-generation neuroleptics improves cognitive flexibility, and there was a relationship between such improvements and normalization of perfusion indices of the involved brain areas.

Differences in visual vs. verbal memory impairments as a result of focal temporal lobe damage in patients with traumatic brain injury.

PRIMARY OBJECTIVE: The aim of the present study was to determine whether the type of lesion in a sample of moderate and severe traumatic brain injury (TBI) was related to material-specific memory impairment. METHODS AND PROCEDURES: Fifty-nine patients with TBI were classified into three groups according to whether the site of the lesion was right temporal, left temporal or diffuse. Six-months post-injury, visual (Warrington's Facial Recognition Memory Test and Rey's Complex Figure Test) and verbal (Rey's Auditory Verbal Learning Test) memories were assessed. MAIN OUTCOME AND RESULTS: Visual memory deficits assessed by facial memory were associated with right temporal lobe lesion, whereas verbal memory performance assessed with a list of words was related to left temporal lobe lesion. The group with diffuse injury showed both verbal and visual memory impairment. CONCLUSIONS: These results suggest a material-specific memory impairment in moderate and severe TBI after focal temporal lesions and a non-specific memory impairment after diffuse damage.

Influence of Angiotensin-converting enzyme polymorphism on neuropsychological subacute performance in moderate and severe traumatic brain injury.

Traumatic brain injury (TBI) frequently results in cerebrovascular lesions that may increase secondary damage and cause neuropsychological impairment. Previous studies suggest an association among the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE), cardiovascular disease, and cognitive performance. Clinical and experimental studies have demonstrated the beneficial effects of ACE inhibitor treatment on vascular injury, hypertension, brain ischemia, and cognitive functioning. In a sample of 73 moderate and severe TBI patients, the authors assessed whether cognitive sequelae differed in relation to the ACE I/D polymorphism. D allele carrier patients performed worse than those with I/I polymorphism on tests involving attention and processing speed. Findings suggest that the physiopathological changes associated with TBI may have greater consequences in ACE D allele carriers.

Hippocampal head atrophy after traumatic brain injury.

Traumatic brain injury (TBI) causes hippocampal damage. The hippocampus can be macroscopically divided into the head, body and tail, which differ in terms of their sensitivity to excitability and also in terms of their cortical connections. We investigated whether damage also varies according to the hippocampal area involved, and studied the relationship of hippocampal reductions with memory performance. Twenty TBI patients and matched controls were examined. MRI measurements were performed separately for the hippocampal head, body and tail. Memory outcome was measured by Rey's auditory verbal learning test, Rey's complex figure test and a modified version of Warrington's facial recognition memory test. Group comparison showed that patients had bilateral hippocampal atrophy, mainly involving the hippocampal head. Moreover, TBI subjects showed verbal memory deficits which presented slight correlations with left hippocampal head atrophy.

Influence of extraneurological insults on ventricular enlargement and neuropsychological functioning after moderate and severe traumatic brain injury.

Extraneurological insults secondary to TBI such as hypotension or hypoxia have been associated with mortality and morbidity. The purpose of this study was to investigate the influence of systemic complications on both neuropsychological outcome and cerebral atrophy. Fifty-seven patients selected from 122 consecutive admissions were studied. Data on the type and severity of injury as well as other systemic insults were collected prior to and during the first 3 days of hospitalization. These data included the presence or absence of a hypoxic episode during the pre-hospital period, the presence and degree of hypoxia, hypercapnia, anemia, hypotension and intracranial hypertension, pupillary reactivity, Glasgow Coma Scale score and coma duration. From the last control CT scan image, performed 6 months post-injury, four different indexes of ventricular dilatation were calculated. Neuropsychological assessment at 6 months included tests of verbal and visual memory, visuoconstructive functions, fine motor speed, and frontal lobe functions. Our results showed that hypoxia and hypotension were related to neuropsychological outcome and long-term ventricular enlargement. Hypoxic episodes prior to hospitalization were related to third ventricle dilatation and to adverse neurological and cognitive outcomes, especially to attention, motor speed, mental flexibility, fluency and verbal memory impairments, suggesting fronto-striatal and hippocampal dysfunction. We conclude that the effect of extraneurological insults on brain structure and function may be as important as the severity of the primary injury.

Neuropsychological correlates of basal ganglia and medial temporal lobe NAA/Cho reductions in traumatic brain injury.

BACKGROUND: Proton magnetic resonance spectroscopy can assess neurochemical sequelae in traumatic brain injury. Metabolic abnormalities are present in the acute or subacute period in patients with traumatic brain injury and correlate with outcome on clinical scales. OBJECTIVE: To investigate the use of proton magnetic resonance spectroscopy in detecting possible gray subcortical neurochemical impairments and their relationship with neuropsychological performance. DESIGN: Group comparisons and correlations of brain metabolites with clinical and neuropsychological variables. PATIENTS AND METHODS: Metabolite concentrations were acquired from voxels localized to the basal ganglia and medial temporal region in 20 patients with long-term moderate and severe traumatic brain injury and 20 matched control subjects. Both groups underwent neuropsychological assessment. RESULTS: N-acetylaspartate-choline-containing compounds ratios were decreased in patients in the basal ganglia (t = -3.28, P =.002) and medial temporal region (t = -3.52, P =.001). The basal ganglia ratio correlated to measures of speed, motor scanning, and attention. CONCLUSION: Patients with long-term TBI present a regional correlation pattern that may help identify the neurological basis of cognitive sequelae in traumatic brain injury.

Magnetic resonance abnormalities associated with cognitive dysfunction in primary Sjögren syndrome.

OBJECTIVE: The aim of the present study was to examine the relationship between magnetic resonance imaging (MRI) findings and cognitive functioning in a group of patients with primary Sjögren Syndrome (SS). METHODS: Fifteen subjects with primary SS and fifteen control subjects diagnosed with migraine were assessed. All subjects received a detailed neuropsychological assessment especially sensitive to fronto-subcortical disorders and a MRI study. Volumetric measures of the ventricular system and intracranial volume and measures of the severity and distribution of signal hyperintensities were obtained. RESULTS: Patients with SS showed larger ventricular volume than control subjects with migraine. The severity of MRI signal hyperintensities and ventricular volume were related to several cognitive and psychiatric variables. CONCLUSION: Patients with primary SS have morphological abnormalities that are related to neuropsychological and psychiatric disturbances. These findings provide some support for the organic etiology of cognitive and psychiatric dysfunction and thus for central nervous system involvement in SS.