Deficits In Domains Research Articles

Peripheral inflammation is associated with impairments of inhibitory behavioral control and visual sensorimotor function in psychotic disorders.

Elevated markers of peripheral inflammation are common in psychosis spectrum disorders and have been associated with brain anatomy, pathology, and physiology as well as clinical outcomes. Preliminary evidence suggests a link between inflammatory cytokines and C-reactive protein (CRP) with generalized cognitive impairments in a subgroup of individuals with psychosis. Whether these patients with elevated peripheral inflammation demonstrate deficits in specific cognitive domains remains unclear. To examine this, seventeen neuropsychological and sensorimotor tasks and thirteen peripheral inflammatory and microvascular markers were quantified in a subset of B-SNIP consortium participants (129 psychosis, 55 healthy controls). Principal component analysis was conducted across the inflammatory markers, resulting in five inflammation factors. Three discrete latent cognitive domains (Visual Sensorimotor, General Cognitive Ability, and Inhibitory Behavioral Control) were characterized based on the neurobehavioral battery and examined in association with inflammation factors. Hierarchical clustering analysis identified cognition-sensitive high/low inflammation subgroups. Among persons with psychotic disorders but not healthy controls, higher inflammation scores had significant associations with impairments of Inhibitory Control (R2=0.100, p-value=2.69e-4, q-value=0.004) and suggestive associations with Visual Sensorimotor function (R2=0.039, p-value=0.024, q-value=0.180), but not with General Cognitive Ability (R2=0.015, p-value=0.162). Greater deficits in Inhibitory Control were observed in the high inflammation patient subgroup, which represented 30.2% of persons with psychotic disorders, as compared to the low inflammation psychosis subgroup. These findings indicate that inflammation dysregulation may differentially impact specific neurobehavioral domains across psychotic disorders, particularly performance on tasks requiring ongoing behavioral monitoring and control.

Utilizing the ISway to Identify and Compare Balance Domain Deficits in People with Multiple Sclerosis

Background and Purpose Balance impairments are a common symptom in people with Multiple Sclerosis (PwMS). The instrumented sway (ISway) is a reliable clinical balance assessment; however, this approach yields a vast range of outcomes that may hinder interpretation and delivery of evidence-based care. Identifying balance domains that are both altered in PwMS and clinically relevant would help isolate treatment targets. Therefore, we sought to develop a multiple sclerosis (MS)-specific model of balance and examine differences between 1) PwMS and neurotypical controls and 2) PwMS with (MS-F) and without a fall history (MS-NF). Methods 118 people with relapsing-remitting MS (MS-F = 39; MS-NF = 79) and 46 age-matched neurotypical controls completed the ISway balance assessment. 22 sway measures obtained from the ISway were entered into an exploratory factor analysis (EFA) to identify underlying balance domains. The model-derived balance domains were compared between 1) PwMS and age-matched, neurotypical controls and 2) MS-F and MS-NF. Results 3 distinct balance domains were identified: 1) sway amplitude and velocity, 2) sway frequency and jerk mediolateral (ML), and 3) sway frequency and jerk anteroposterior (AP), explaining 81.66% of balance variance. PwMS exhibited worse performance (i.e., greater amplitude and velocity of sway) in the sway velocity and amplitude domain compared to age-matched neurotypical controls (p = .003). MS-F exhibited worse performance in the sway velocity and amplitude domain compared to MS-NF (p = 0.046). The AP and ML sway frequency and jerk domains were not different between PwMS and neurotypical controls nor between MS-F and MS-NF. Discussion PwMS exhibited deficits within the sway amplitude and velocity domain compared to neurotypical controls, with a similar effect observed between MS-F and MS-NF. Recognizing balance domains altered in PwMS and related to falls may be useful for efficient and strategic balance assessment and rehabilitation. Balance impairments are a common symptom in people with Multiple Sclerosis (PwMS). The instrumented sway (ISway) is a reliable clinical balance assessment; however, this approach yields a vast range of outcomes that may hinder interpretation and delivery of evidence-based care. Identifying balance domains that are both altered in PwMS and clinically relevant would help isolate treatment targets. Therefore, we sought to develop a multiple sclerosis (MS)-specific model of balance and examine differences between 1) PwMS and neurotypical controls and 2) PwMS with (MS-F) and without a fall history (MS-NF). 118 people with relapsing-remitting MS (MS-F = 39; MS-NF = 79) and 46 age-matched neurotypical controls completed the ISway balance assessment. 22 sway measures obtained from the ISway were entered into an exploratory factor analysis (EFA) to identify underlying balance domains. The model-derived balance domains were compared between 1) PwMS and age-matched, neurotypical controls and 2) MS-F and MS-NF. 3 distinct balance domains were identified: 1) sway amplitude and velocity, 2) sway frequency and jerk mediolateral (ML), and 3) sway frequency and jerk anteroposterior (AP), explaining 81.66% of balance variance. PwMS exhibited worse performance (i.e., greater amplitude and velocity of sway) in the sway velocity and amplitude domain compared to age-matched neurotypical controls (p = .003). MS-F exhibited worse performance in the sway velocity and amplitude domain compared to MS-NF (p = 0.046). The AP and ML sway frequency and jerk domains were not different between PwMS and neurotypical controls nor between MS-F and MS-NF. PwMS exhibited deficits within the sway amplitude and velocity domain compared to neurotypical controls, with a similar effect observed between MS-F and MS-NF. Recognizing balance domains altered in PwMS and related to falls may be useful for efficient and strategic balance assessment and rehabilitation.

Dramatic Improvement of MRI Abnormalities of HIV Dementia after Suppressive Antiretroviral Therapy (S25.002)

<h3>Objective:</h3> Not applicable. <h3>Background:</h3> A 59-year-old man diagnosed with HIV 26 years prior and a long history of antiretroviral therapy (ART) non-adherence presented with subacute cognitive decline. A neurologic workup including cerebrospinal fluid testing showed no evidence of opportunistic infections. He was admitted to an assisted care facility where he restarted ART. However, he remained viremic and was referred to the National Institutes of Health (NIH). On admission to the NIH, he had an HIV plasma viral load of 28,056 copies/mL and CD4 T-cell count of 5 cells/μL. He was started on a new ART regimen with increased central nervous system penetration (etravirine, dolutegravir, darunavir/cobicistat, tenofovir/emtricitabine). MRI revealed extensive leukoencephalopathy and volume loss, consistent with HIV encephalopathy. Comprehensive neuropsychological testing revealed significant deficits in all cognitive domains, including learning, memory, attention, executive function, and psychomotor speed. The patient was followed for two years, during which time he achieved and sustained viral suppression (&lt;40 copies/mL) and reached a CD4 T-cell count of 197 with ART. A repeat MRI showed profound improvement in the white matter signal abnormality. Repeat neuropsychological testing demonstrated notable improvements in several tests of attention, information processing, and psychomotor speed, but continued difficulty in most other cognitive domains. <h3>Design/Methods:</h3> Not applicable. <h3>Results:</h3> Not applicable. <h3>Conclusions:</h3> While current ART regimens are highly effective in reducing the incidence of HIV-associated neurologic complications, their role in reversing the MRI abnormalities seen in HIV encephalopathy remains unclear. In this case, we tracked HIV encephalopathy in the current era of effective ART with serial MRI evaluations. Our results provide a rare example of dramatic reduction of periventricular white matter hyperintensities and improved performance in a subset of cognitive domains. Providers encountering white matter abnormalities in patients with treated HIV should consider this legacy effect in evaluating whether disease is progressive, or as in this case, improved. <b>Disclosure:</b> Ms. Dietrich has nothing to disclose. Miss Laidlaw has nothing to disclose. Dr. Hammoud has nothing to disclose. Dr. Pau has nothing to disclose. Dr. Smith has nothing to disclose.

Profiles of cognitive impairment in chronic heart failure-A cluster analytic approach.

Cognitive impairment is a major comorbidity in patients with chronic heart failure (HF) with a wide range of phenotypes. In this study, we aimed to identify and compare different clusters of cognitive deficits. The prospective cohort study "Cognition.Matters-HF" recruited 147 chronic HF patients (aged 64.5 ± 10.8 years; 16.2% female) of any etiology. All patients underwent extensive neuropsychological testing. We performed a hierarchical cluster analysis of the cognitive domains, such as intensity of attention, visual/verbal memory, and executive function. Generated clusters were compared exploratively with respect to the results of cardiological, neurological, and neuroradiological examinations without correction for multiple testing. Dendrogram and the scree plot suggested three distinct cognitive profiles: In the first cluster, 42 patients (28.6%) performed without any deficits in all domains. Exclusively, the intensity of attention deficits was seen in the second cluster, including 55 patients (37.4%). A third cluster with 50 patients (34.0%) was characterized by deficits in all cognitive domains. Age (p = 0.163) and typical clinical markers of chronic HF, such as ejection fraction (p = 0.222), 6-min walking test distance (p = 0.138), NT-proBNP (p = 0.364), and New York Heart Association class (p = 0.868) did not differ between clusters. However, we observed that women (p = 0.012) and patients with previous cardiac valve surgery (p = 0.005) prevailed in the "global deficits" cluster and the "no deficits" group had a lower prevalence of underlying arterial hypertension (p = 0.029). Total brain volume (p = 0.017) was smaller in the global deficit cluster, and serum levels of glial fibrillary acidic protein were increased (p = 0.048). Apart from cognitively healthy and globally impaired HF patients, we identified a group with deficits only in the intensity of attention. Women and patients with previous cardiac valve surgery are at risk for global cognitive impairment when suffering HF and could benefit from special multimodal treatment addressing the psychosocial condition.

Anemia and Erythrocyte Indices Are Associated With Neurocognitive Performance Across Multiple Ability Domains in Adults With HIV.

Anemia is linked to neurocognitive impairment (NCI) in people with HIV (PWH), but its impact within specific ability domains, and in diverse populations with HIV, is uncertain. Participants included 1339 PWH enrolled in observational HIV cohort studies with a mean of 3 comprehensive neurocognitive assessments over 30 months. Global and domain-specific neurocognitive function were assessed by the global deficit score and domain deficit score (GDS and DDS, respectively) or as GDS-defined or DDS-defined NCI (GDS ≥ 0.5, DDS > 0.5). Time-dependent associations of anemia or red-cell indices with neurocognitive function were evaluated by multivariable regression. The mean age at entry was 43.6 years (85% male, 23.9% Hispanic, 16.7% African ancestry by self-report, and 69.8% virally suppressed). Anemia occurred at entry in 297 (22.2%) and developed subsequently in another 129 (9.6%). Anemia (present in 26.8% of cognitively impaired PWH at entry) and lower hemoglobin were associated with higher (worse) GDS values; the association for anemia persisted after multivariable adjustment and in virally suppressed persons ( P < 0.0001). Anemia was also associated with reduced processing speed, motor function, learning, delayed recall, working memory (all P < 0.01), executive function ( P = 0.021), and verbal fluency ( P = 0.035), and these findings persisted in longitudinal analyses (adjusted P < 0.01 for all domains, except verbal fluency). Higher mean corpuscular volume and mean corpuscular hemoglobin were associated with less impairment in learning and recall (all P < 0.05). Anemia in diverse and virally suppressed PWH associates with reduced neurocognitive performance in multiple domains, cross-sectionally and over time. The impact of identifying and treating anemia to prevent or slow neurocognitive decline in PWH should be prospectively evaluated.

Using the Instrumented Sway System (ISway) to Identify and Compare Balance Domain Deficits in People With Multiple Sclerosis

ObjectiveTo develop a multiple sclerosis (MS)-specific model of balance and examine differences between (1) MS and neurotypical controls and (2) people with MS (PwMS) with (MS-F) and without a fall history (MS-NF). Design and SettingA cross-sectional study was conducted at the Gait and Balance Laboratory at the University of Kansas Medical Center. Balance was measured from the instrumented sway system (ISway) assessment. ParticipantsIn total, 118 people with relapsing-remitting MS (MS-F=39; MS-NF=79) and 46 age-matched neurotypical controls. InterventionNot applicable. Outcome MeasuresA total of 22 sway measures obtained from the ISway were entered into an exploratory factor analysis to identify underlying balance domains. The model-derived balance domains were compared between (1) PwMS and age-matched, neurotypical controls and (2) MS-F and MS-NF. ResultsThree distinct balance domains were identified: (1) sway amplitude and velocity, (2) sway frequency and jerk mediolateral, and (3) sway frequency and jerk anteroposterior, explaining 81.66% of balance variance. PwMS exhibited worse performance (ie, greater amplitude and velocity of sway) in the sway velocity and amplitude domain compared to age-matched neurotypical controls (P=.003). MS-F also exhibited worse performance in the sway velocity and amplitude domain compared to MS-NF (P=.046). The anteroposterior and mediolateral sway frequency and jerk domains were not different between PwMS and neurotypical controls nor between MS-F and MS-NF. ConclusionsThis study identified a 3-factor, MS-specific balance model, demonstrating that PwMS, particularly those with a fall history, exhibit disproportionate impairments in sway amplitude and velocity. Identifying postural stability outcomes and domains that are altered in PwMS and clinically relevant (eg, related to falls) would help isolate potential treatment targets.

Functional and structural brain abnormalities in substance use disorder: A multimodal meta-analysis of neuroimaging studies.

Numerous neuroimaging studies of resting-state functional imaging and voxel-based morphometry (VBM) have revealed that patients with substance use disorder (SUD) may present brain abnormalities, but their results were inconsistent. This multimodal neuroimaging meta-analysis aimed to estimate common and specific alterations in SUD patients by combining information from all available studies of spontaneous functional activity and gray matter volume (GMV). A whole-brain meta-analysis on resting-state functional imaging and VBM studies was conducted using the Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) software, followed by multimodal overlapping to comprehensively investigate function and structure of the brain in SUD. In this meta-analysis, 39 independent studies with 47 datasets related to resting-state functional brain activity (1444 SUD patients; 1446 healthy controls [HCs]) were included, as well as 77 studies with 89 datasets for GMV (3457 SUD patients; 3774 HCs). Patients with SUD showed the decreased resting-state functional brain activity in the bilateral anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC). For the VBM meta-analysis, patients with SUD showed the reduced GMV in the bilateral ACC/mPFC, insula, thalamus extending to striatum, and left sensorimotor cortex. This multimodal meta-analysis exhibited that SUD shows common impairment in both function and structure in the ACC/mPFC, suggesting that the deficits in functional and structural domains could be correlated together. In addition, a few regions exhibited only structural impairment in SUD, including the insula, thalamus, striatum, and sensorimotor areas.

Differential Impact of Brain Network Efficiency on Poststroke Motor and Attentional Deficits.

Most studies on stroke have been designed to examine one deficit in isolation; yet, survivors often have multiple deficits in different domains. While the mechanisms underlying multiple-domain deficits remain poorly understood, network-theoretical methods may open new avenues of understanding. Fifty subacute stroke patients (7±3days poststroke) underwent diffusion-weighted magnetic resonance imaging and a battery of clinical tests of motor and cognitive functions. We defined indices of impairment in strength, dexterity, and attention. We also computed imaging-based probabilistic tractography and whole-brain connectomes. To efficiently integrate inputs from different sources, brain networks rely on a rich-club of a few hub nodes. Lesions harm efficiency, particularly when they target the rich-club. Overlaying individual lesion masks onto the tractograms enabled us to split the connectomes into their affected and unaffected parts and associate them to impairment. We computed efficiency of the unaffected connectome and found it was more strongly correlated to impairment in strength, dexterity, and attention than efficiency of the total connectome. The magnitude of the correlation between efficiency and impairment followed the order attention>dexterity ≈ strength (strength: |r|=.03, P=0.02, dexterity: |r|=.30, P=0.05, attention: |r|=.55, P<0.001). Network weights associated with the rich-club were more strongly correlated to efficiency than non-rich-club weights. Attentional impairment is more sensitive to disruption of coordinated networks between brain regions than motor impairment, which is sensitive to disruption of localized networks. Providing more accurate reflections of actually functioning parts of the network enables the incorporation of information about the impact of brain lesions on connectomics contributing to a better understanding of underlying stroke mechanisms.

Differential expression of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) in Alzheimer's disease and HIV-1 associated neurocognitive disorders

The United Nations projects that one in every six people will be over the age of 65 by the year 2050. With a rapidly aging population, the risk of Alzheimer's disease (AD) becomes a major concern. AD is a multifactorial disease that involves neurodegeneration in the brain with mild dementia and deficits in memory and other cognitive domains. Additionally, it has been established that individuals with Human Immunodeficiency Virus-1 (HIV-1) experience a 5 to 10-year accelerated aging and an increased risk of developing HIV-associated neurocognitive disorders (HAND). Despite a significant amount of clinical evidence pointing towards a potential overlap between neuropathogenic processes in HAND and AD, the underlying epigenetic link between these two diseases is mostly unknown. This study is focused on identifying differentially expressed genes observed in both AD and HAND using linear regression models and a more robust significance analysis of microarray. The results established that the dysregulated type 1 and 2 interferon pathways observed in both AD and HAND contribute to the similar pathologies of these diseases within the brain. The current study identifies the important roles of interferon pathways in AD and HAND, a relationship that may be useful for earlier detection in the future.

Neurocognitive Deficits in First-Episode and Chronic Psychotic Disorders: A Systematic Review from 2009 to 2022.

Cognitive impairment in patients suffering from schizophrenia spectrum disorders has been discussed as a strong predictor for multiple disease outcome variables, such as response to psychotherapy, stable relationships, employment, and longevity. However, the consistency and severity of cognitive deficits across multiple domains in individuals with first-episode and chronic psychotic disorders is still undetermined. We provide a comprehensive overview of primary research from the years 2009 to 2022. Based on a Cochrane risk assessment, a systematic synthesis of 51 out of 3669 original studies was performed. Impairment of cognitive functioning in patients diagnosed with first-episode psychotic disorders compared with healthy controls was predicted to occur in all assessed cognitive domains. Few overall changes were predicted for chronically affected patients relative to those in the first-episode stage, in line with previous longitudinal studies. Our research outcomes support the hypothesis of a global decrease in cognitive functioning in patients diagnosed with psychotic disorders, i.e., the occurrence of cognitive deficits in multiple cognitive domains including executive functioning, memory, working memory, psychomotor speed, and attention. Only mild increases in the frequency of cognitive impairment across studies were observed at the chronically affected stage relative to the first-episode stage. Our results confirm and extend the outcomes from prior reviews and meta-analyses. Recommendations for psychotherapeutic interventions are provided, considering the broad cognitive impairment already observed at the stage of the first episode. Based on the risk of bias assessment, we also make specific suggestions concerning the quality of future original studies.

Gestational age at birth and cognitive outcomes in adolescence: population based full sibling cohort study

ObjectiveTo investigate the association between gestational age at birth and cognitive outcomes in adolescence.DesignNationwide population based full sibling cohort study.SettingDenmark.Participants1.2 million children born between 1 January 1986 and 31 December...

Response to Preoperative Dexamethasone Predicts Postoperative Neurological Improvement of Focal Neurological Deficits in Patients With Brain Metastases.

Steroids are used ubiquitously in the preoperative management of patients with brain tumor. The rate of improvement in focal deficits with steroids and the prognostic value of such a response are not known. To determine the rate at which focal neurological deficits respond to preoperative corticosteroids in patients with brain metastases and whether such an improvement could predict long-term recovery of neurological function after surgery. Patients with brain metastases and related deficits in language, visual field, or motor domains who received corticosteroids before surgery were identified. Characteristics between steroid responders and nonresponders were compared. Ninety six patients demonstrated a visual field (13 patients), language (19), or motor (64) deficit and received dexamethasone in the week before surgery (average cumulative dose 43 mg; average duration 2.7 days). 38.5% of patients' deficits improved with steroids before surgery, while 82.3% of patients improved by follow-up. Motor deficits were more likely to improve both preoperatively ( P = .014) and postoperatively ( P = .010). All 37 responders remained improved at follow-up whereas 42 of 59 (71%) of nonresponders ultimately improved ( P < .001). All other clinical characteristics, including dose and duration, were similar between groups. A response to steroids before surgery is highly predictive of long-term improvement postoperatively in brain metastasis patients with focal neurological deficits. Lack of a response portends a somewhat less favorable prognosis. Duration and intensity of therapy do not seem to affect the likelihood of response.

Initial Severity of Injury Has Little Effect on the Temporal Profile of Long-Term Deficits in Locomotion, Anxiety, and Cognitive Function After Diffuse Traumatic Brain Injury.

Traumatic brain injury (TBI) is associated with persistent impairments in multiple domains, including cognitive and neuropsychiatric function. Previous literature has suggested that the risk of such impairments may differ as a function of the initial severity of injury, with moderate-severe TBI (msTBI) associated with more severe cognitive dysfunction and mild TBI (mTBI) associated with a higher risk of developing an anxiety disorder. Despite this, relatively few pre-clinical studies have investigated the time course of behavioral change after different severities of injury. The current study compared the temporal profile of functional deficits incorporating locomotion, cognition, and anxiety up to 12 months post-injury after an mTBI, repeated mild TBI (rmTBI), and single msTBI in an experimental model of diffuse TBI. Injury appeared to alter the effect of aging on locomotor activity, with both msTBI and rmTBI rats showing a decrease in locomotion at 12 months relative to their earlier performance on the task, an effect not observed in shams or after a single mTBI. Further, mTBI seemed to be associated with decreased anxiety over time, as measured by increased time spent in the open arm of the elevated plus maze from 3 to 12 months post-injury. No significant findings were observed on spatial memory or volumetric magnetic resonance imaging. Future studies will need to use a more comprehensive behavioral battery, capable of capturing subtle alterations in function, and longer time points, following rats into old age, in order to more fully assess the evolution of persistent behavioral deficits in key domains after different severities of TBI, as well as their accompanying neuroimaging changes. Given the prevalence and significance of such deficits post-TBI for a person's quality of life, as well as the elevated risk of neurodegenerative disease post-injury, such investigations may play a critical role in identifying optimal windows of therapeutic intervention post-injury.

A common low dimensional structure of cognitive impairment in stroke and brain tumors

IntroductionNeuropsychological studies infer brain-behavior relationships from focal lesions like stroke and tumors. However, these pathologies impair brain function through different mechanisms even when they occur at the same brain’s location. The aim of this study was to compare the profile of cognitive impairment in patients with brain tumors vs. stroke and examine the correlation with lesion location in each pathology. MethodsPatients with first time stroke (n = 77) or newly diagnosed brain tumors (n = 76) were assessed with a neuropsychological battery. Their lesions were mapped with MRI scans. Test scores were analyzed using principal component analysis (PCA) to measure their correlation, and logistic regression to examine differences between pathologies. Next, with ridge regression we examined whether lesion features (location, volume) were associated with behavioral performance. ResultsThe PCA showed a similar cognitive impairment profile in tumors and strokes with three principal components (PCs) accounting for about half of the individual variance. PC1 loaded on language, verbal memory, and executive/working memory; PC2 loaded on general performance, visuo-spatial attention and memory, and executive functions; and, PC3 loaded on calculation, reading and visuo-spatial attention. The average lesion distribution was different, and lesion location was correlated with cognitive deficits only in stroke. Logistic regression found language and calculation more affected in stroke, and verbal memory and verbal fluency more affected in tumors. ConclusionsA similar low dimensional set of behavioral impairments was found both in stroke and brain tumors, even though each pathology caused some specific deficits in different domains. The lesion distribution was different for stroke and tumors and correlated with behavioral impairment only in stroke.

Poruchy fetálneho alkoholového spektra u detí v období raného veku

Fetal alcohol spectrum disorders is an umbrella term for a group of congenital neurodevelopmental defects and brain damage, the main cause of which is prenatal alcohol exposure. Alcohol consumption during the mother’s pregnancy has serious effects on the development of children at an early age, which can be manifested at the physical and neurobehavioral areas. Children at different stages of early childhood development show specific behaviors and deficits in individual domains of development. Deficits are highly variable in individual children. Screening and subsequent availability of early diagnosis and intervention is important, including various early intervention strategies specific to FASD.

Multimodal intervention in 8- to 13-year-old French dyslexic readers: Study protocol for a randomized multicenter controlled crossover trial

BackgroundDevelopmental dyslexia, a specific and long-lasting learning disorder that prevents children from becoming efficient and fluent readers, has a severe impact on academic learning and behavior and may compromise professional and social development. Most remediation studies are based on the explicit or implicit assumption that dyslexia results from a single cause related to either impaired phonological or visual-attentional processing or impaired cross-modal integration. Yet, recent studies show that dyslexia is multifactorial and that many dyslexics have underlying deficits in several domains. The originality of the current study is to test a remediation approach that trains skills in all three domains using different training methods that are tailored to an individual’s cognitive profile as part of a longitudinal intervention study.MethodsThis multicenter randomized crossover study will be conducted in three phases and will involve 120 dyslexic children between the ages of 8 and 13 years. The first phase serves as within-subject baseline period that lasts for 2 months. In this phase, all children undergo weekly speech-language therapy sessions without additional training at home (business-as-usual). During the second phase, all dyslexics receive three types of intensive interventions that last 2 month each: Phonological, visual-attentional, and cross-modal. The order of the first two interventions (phonological and visual-attentional) is swapped in two randomly assigned groups of 60 dyslexics each. This allows one to test the efficacy and additivity of each intervention (against baseline) and find out whether the order of delivery matters. During the third phase, the follow-up period, the intensive interventions are stopped, and all dyslexics will be tested after 2 months. Implementation fidelity will be assessed from the user data of the computerized intervention program and an “intention-to-treat” analysis will be performed on the children who quit the trial before the end.DiscussionThe main objective of this study is to assess whether the three types of intensive intervention (phase 2) improve reading skills compared to baseline (i.e., non-intensive intervention, phase 1). The secondary objectives are to evaluate the effectiveness of each intervention and to test the effects of order of delivery on reading intervention outcomes. Reading comprehension, spelling performance and reading disorder impact of dyslexic readers are assessed immediately before and after the multimodal intervention and 2 months post-intervention.Trial registrationClinicalTrials.gov, NCT04028310. Registered on July 18, 2019.

Neurocognitive considerations in the treatment of meningioma with radiation therapy: applications for quantitative neuroimaging and precision radiation medicine.

This article focuses on the role of radiotherapy in the management of meningioma, in the definitive and adjuvant setting and across the spectrum of meningioma grade. Treatment paradigms, informed by clinical evidence, are discussed. Notably, we focus on the impact of radiotherapy on normal brain tissues and neurocognitive function, particularly the dose-dependent changes in white matter and cerebral cortex thickness. Novel imaging techniques have allowed the identification of microstructural changes to eloquent white matter, cortex, and subcortical regions as biomarkers for understanding RT-induced changes in cognitive functioning. Deficits in multiple domains including attention, memory, language and executive function can become more pronounced following radiation. Longitudinal assessment with imaging and neurocognitive testing pre- and post-radiation have allowed correlation between dose to specific regions of the brain and decline in associated domains of neurocognitive function. These findings suggest incorporation of areas at higher risk for neurocognitive sequelae into precision radiation planning. Volumetric arc therapy, advanced planning with cortical sparing, proton therapy and stereotactic radiosurgery are reviewed as options for delivering therapeutic dose to target volumes while minimizing risk to adjacent sensitive regions. The treatment of meningioma is an evolving area, with improving outcomes for higher grade disease in modern trials, where care must be taken to maximize both disease control as well as quality of life for patients.

Findings of a Multidisciplinary Assessment of Children Referred for Possible Neurodevelopmental Disorders: Insights from a Retrospective Chart Review Study.

Children with ASD have a wide spectrum of functional deficits in multiple neurodevelopmental domains. A multidisciplinary team assessment (MDT) is required to assess those deficits to help construct a multimodal intervention plan. This is a retrospective chart review of the assessment for children who were referred for an assessment of potential neurodevelopmental disorders. We reviewed 221 participants' charts from January 2019 to January 2020. The mean age of the children was 7.95 ± 3.69, while the mean age of the fathers and mothers was 37.31 ± 8.57 and 31.95 ± 6.93, respectively. Consanguinity was as high as 37.9% for the referred children with developmental delay who were first-degree related, and 13.2% of the parents were second-degree relatives. Approximately 26.6% of children had a family history of mental illness in first-degree relatives. ASD was the most commonly reported diagnosis post-assessment, and ADHD was the most common reported comorbidity at 64.3% and 88.5%, respectively. The MDT findings showed that 58% of children required moderate or higher assistance with toileting, 79.2% were unable to answer yes/no questions, and 86.8% were unable to understand "wh" questions. Only 26% of the nonverbal children had average IQ testing results, and 31% of verbal children did. In conclusion, the mean age of the children when assessed was above that recommended for early screening and intervention. An increased paternal and maternal age was noticeable. Consanguinity and a family history of mental disorders in first-degree relatives were high, attesting to a possible genetic risk.

Deficits in Different Cognitive Domains Predict the Progression of Amnestic Mild Cognitive Impairment: A Literature Review

Introduction: Mild cognitive impairment (MCI) is a heterogeneous syndrome in which older adults show cognitive deficits that do not interfere with daily living. Amnestic mild cognitive impairment (aMCI) is a subtype of MCI where episodic memory is significantly impaired and considered the transition stage between normal aging and Alzheimer’s disease (AD). The cognitive profiles of individuals with aMCI may predict various trajectories and inform the risk of AD conversion. Given that cognitive domains beyond memory including language and executive functioning (EF) may contribute to the progression of aMCI, this paper will examine how deficits in these three domains can be used to predict trajectories of the syndrome. Methods: PUBMED, EMBASE, and CINAHL databases were used to screen for studies to construct this systematic review. A total of 20 studies were reviewed. Results: Functional changes in memory were observed including the diminished performance in the encoding and recognition phases of episodic memory, associative recall, rapid forgetting, and pattern separation in individuals with aMCI relative to age-matched peers. Overall EF and all three core EF components studied were impaired to similar extents. Dynamic working memory and verbal memory performance was impaired to a greater extent in individuals with multiple- domain aMCI (a more severe subtype of aMCI) relative to single-domain aMCI. Language impairments were associated with AD pathology, including verbal fluency deficits and semantic verbal fluency patterns, all of which were further impaired in individuals with multiple-domain aMCI relative to single-domain aMCI. Discussion: Structural and functional changes in the medial temporal lobe (MTL) underlie various deficits in memory, EF, and language domains. Research suggests that individuals with single-domain aMCI perform more similarly with healthy controls, while those with multiple-domain aMCI perform more similarly with individuals with AD. This is likely attributed to cognitive domains beyond memory having a drastic impact on aMCI pathogenesis. Conclusion: Preliminary evidence offers support for a more nuanced use of cognitive profiles to determine future outcomes and take appropriate clinical action earlier for improved prognosis and therapeutic plan development. Earlier formulation of treatment methods could drastically increase the likelihood of slowing or even reversing aMCI pathogenesis.

Assessment of balance in people with mild traumatic brain injury using a balance systems model approach

PurposeMeasuring persistent imbalance after mTBI is challenging and may include subjective symptom-reporting as well as clinical scales. Clinical assessments for quantifying balance following mTBI have focused on sensory orientation. It is theorized that balance control goes beyond sensory orientation and also includes subdomains of anticipatory postural adjustments, reactive postural control, and dynamic gait. The Mini Balance Evaluation Systems Test (Mini-BESTest) is a validated balance test that measures balance according to these subdomains for a more comprehensive assessment. The purpose of this study was to compare Mini-BESTest total and subdomain scores after subacute mTBI with healthy controls. MethodsSymptomatic mTBI (n = 90, 20 % male, age=36.0 ± 12.0, 46.3.4 ± 22.1 days since injury) and healthy control (n = 45, 20 % male, age=35.4 ± 12.5) participants completed the Mini-BESTest for balance. Mini-BESTest between-group differences were evaluated using Wilcoxon rank-sum tests. ResultsThe mTBI group (Median[minimum,maximum]) had a significantly worse Mini-BESTest total score than the healthy controls (24[18,28] vs 27[23–28], p < 0.001). The mTBI group performed significantly worse in 3 of the 4 subdomains compared to the healthy controls: reactive postural control: 5[2–6] vs 6[3–6], p = 0.003; sensory orientation: 6[5,6] vs 6[6], p = 0.005; dynamic gait: 8[5–10] vs 9[8–10], p < 0.001. There was no significance difference between groups in the anticipatory postural adjustments domain (5[3–6] vs 5[3–6], p = 0.12). ConclusionsThe Mini-BESTest identified deficits in people with subacute mTBI in the total score and 3 out of 4 subdomains, suggesting it may be helpful to use in the clinic to identify balance subdomain deficits in the subacute mTBI population. In combination with self-reported assessments, the mini-BESTest may identify balance domain deficits in the subacute mTBI population and help guide treatment for this population.