Cognitive Behavioural Assessment Research Articles

Introversion, Alexithymia, and Hostility: A Path Analysis From Personality to Suicidal Ideation Among University Students.

The aim of the current study was to investigate the relationship between state (i.e., hostility) and trait (i.e., social detachment, alexithymia) psychological constructs associated with suicidal ideation among university students. A group of 190 university students was consecutively recruited in the period between September 2022 and March 2023. After a clinical interview, a series of psychological tests were administered: the Cattell's 16-Personality Factors Questionnaire (16PF), the Toronto Alexithymia Scale (TAS-20), the Symptom Checklist-90-R (SCL-90-R), and the anamnestic form of the Cognitive Behavioral Assessment (CBA2.0), which contains a specific question regarding the suicidal ideation. The analyses demonstrated that alexithymia fully mediated the relationship between a particular aspect of introversion (social detachment or low warmth) and hostility which, in turn, seemed to be a significant predictor of suicidal ideation. The path analysis conducted seemed to highlight the importance of personality traits, such as social detachment and the ability to recognize and express one's internal states, on the mental health of university students in terms of hostility and suicidal ideation. Considering that the reduction of suicide mortality has been prioritized as a global target in the 15-19 age group, identifying the psychological factors associated with it is fundamental.

Determinants of self-perceived quality of life in mildly disabled multiple sclerosis patients: a cross-sectional study.

While the determinants influencing self-perceived health-related quality of life (spHRQoL) in persons with multiple sclerosis (pwMS) and severe physical impairment have been well investigated, their impact on pwMS with mild disability is poorly addressed. We aimed to investigate possible drivers of spHRQoL among Sardinian pwMS with an EDSS lower than 2.5. A sample of 87 fully ambulatory (EDSS < 2.5) pwMS were included after screening for major cognitive impairment. spHRQoL was measured with the Italian version of 36-Item Short Form Health Survey (SF-36). The Physical Component Summary (PCS) and Mental Component Summary (MCS) were used as dependent variables for univariate analysis with Cognitive Behavioral Assessment (CBA) and specific individual factors as independent variables. Subsequent multivariate general linear models (GLMs) for PCS and MCS respectively were run after stepwise regression. Normative data referring to Italian population were used for comparison. As compared to normative data, no statistically significant difference was found for PCS, while MCS was reduced. Multivariate GLMs showed a significant association between lower PCS scores and presence of psychosomatic symptoms, older age and fatigue (p < 0.05). Furthermore, a significant association was shown between lower MCS scores and presence of anxiety (p < 0.001). Mood, presence of psychosomatic symptoms, fatigue and age can have a relevant impact on spHRQoL in people with mildly disabling MS and should be considered in the management of such individuals.

Intranasal Administration of Mesenchymal Stem Cell-Derived Exosome Alleviates Hypoxic-Ischemic Brain Injury.

Hypoxic-ischemic brain injury arises from inadequate oxygen delivery to the brain, commonly occurring following cardiac arrest, which lacks effective treatments. Recent studies have demonstrated the therapeutic potential of exosomes released from mesenchymal stem cells. Given the challenge of systemic dilution associated with intravenous administration, intranasal delivery has emerged as a promising approach. In this study, we investigate the effects of intranasally administered exosomes in an animal model. Exosomes were isolated from the cell supernatants using the ultracentrifugation method. Brain injury was induced in Sprague-Dawley rats through a transient four-vessel occlusion model. Intranasal administration was conducted with 3 × 108 exosome particles in 20 µL of PBS or PBS alone, administered daily for 7 days post-injury. Long-term cognitive behavioral assessments, biodistribution of exosomes, and histological evaluations of apoptosis and neuroinflammation were conducted. Exosomes were primarily detected in the olfactory bulb one hour after intranasal administration, subsequently distributing to the striatum and midbrain. Rats treated with exosomes exhibited substantial improvement in cognitive function up to 28 days after the insult, and demonstrated significantly fewer apoptotic cells along with higher neuronal cell survival in the hippocampus. Exosomes were found to be taken up by microglia, leading to a decrease in the expression of cytotoxic inflammatory markers.

CSF levels of the synaptic marker Cyclase‐associated protein CAP2 in Alzheimer disease across clinical stages

AbstractBackgroundSynaptic dysfunction represent a key event in cognitive decline in Alzheimer disease. There is evidence that Cyclase‐associated protein 2 (CAP2) is involved in synaptic plasticity in AD models but its role in clinical setting has never extensively assessed. Aim of this study was to evaluate CAP2 levels in cerebrospinal fluids of AD and other neurodegenerative diseases and their relationship with amyloid and tau related biomarkers.Methodone‐hundred ten AD patients (prodromal AD n = 70; mild to moderate AD n = 40), 20 Lewy Body Dementia (LBD), 20 frontotemporal dementia (FTD) and 40 healthy controls (HC) were investigated and clinically assessed following a standardized neurological and cognitive behavioral assessment. All subjects underwent CSF analyses for h‐tau, p‐tau and Aß42 (Lumipulse) while CAP2 levels were assessed by using standard ELISA. Between‐groups differences and correlations between CSF biomarkers were evaluated using non‐parametric comparisons and partial correlation analyses adjusted for the effect of age, sex and disease duration.ResultAD patients across severity stages showed higher CAP2 levels compared to controls and non‐AD patients (p = 0.001). CAP2 levels did not correlate with disease severity and were independent of APOE genotype. In AD patients, CAP2 levels showed a positive correlation with t‐tau and p‐tau (p&lt;0.001).ConclusionCSF levels of CAP2 were significantly increased in AD patients and correlated with t‐tau and p‐tau independently of amyloid pathology. Altogether, these findings support the hypothesis that AD is specifically associated with synaptic dysfunction since early stages and that amyloid‐related synaptic changes parallels tau‐related axonal degeneration.

Sulfanegen, a 3‐mercaptopyruvate sulfurtransferase substrate, as a therapeutic option for Alzheimer’s disease

AbstractBackgroundThe oxidative stress evident in the Alzheimer’s disease (AD) brain leads to compromised 3‐mercaptopyruvate sulfurtransferase (3MST) function, one of the endogenous hydrogen sulfide (H2S) producing enzymes.1,2 Impaired 3MST function is expected to contribute toward potentiation of oxidative stress by depleting cellular glutathione (GSH) stores, and exacerbation of AD pathology by enhancing Aβ aggregation resulting in neurodegeneration. Preclinical studies with H2S donors such as NaSH have been promising,3,4 however further clinical translation efforts are thwarted due to their poor chemical stability, bioavailability, and dose‐limiting toxicities. We have developed a stable, bioavailable prodrug of 3MST substrate 3‐mercaptopyruvate, named sulfanegen, which can supplement the enzymatic reaction releasing H2S.2 Thus provision of sulfanegen could prove beneficial in mitigating AD‐related neurodegenerative consequences.MethodAged, symptomatic cohorts APP/PS1 mice (7 and 12 month old) were treated with saline (N = 8) or sulfanegen (75 mg/kg, i.p., N = 8) for 12 weeks. Cognitive behavioral assessments (T‐maze) were conducted 10‐11 weeks after treatment initiation. Equal numbers of both sexes of mice were used as much as possible. The harvested brain tissues were analyzed biochemically for cortical/hippocampal Aβ1‐42 burden, oxidative stress and inflammatory markers (protein carbonyls, lipid peroxidation, glutathione assay, TNF‐α and IL6. Quantitative stereological analysis of Aβ pathology, neuroinflammation and progressive neurodegeneration were also conducted.ResultTreatment of symptomatic Alzheimer’s mice with sulfanegen prevented cognitive impairment resulting from AD pathology (Figure 1).2 This was corroborated by reduced brain amyloid load as well as the reversal of oxidative stress and neuroinflammation. Neuropathological analysis also displayed modest, but significant effect of sulfanegen on Aβ levels, reactive astrogliosis and microglial reactivity. More importantly, sulfanegen caused attenuation of progressive degeneration of noradrenergic system in the LC. Additionally, administration of sulfanegen supplemented brain 3MP levels, resulting in restoration of brain 3MST function.ConclusionCollectively, our results show that the provision of a 3MST substrate, sulfanegen, exhibits neuroprotective effects, along with restoration of cognitive function in an AD mouse model. This study suggests an important role of 3MST in AD pathophysiology and potential therapeutic utility of sulfanegen as a disease‐modifying treatment.

Study protocol of a clinical randomized controlled trial on the efficacy of an innovative Digital thErapy to proMote wEighT loss in patients with obesity by incReasing their Adherence to treatment: the DEMETRA study

Despite the increasing importance of innovative medications and bariatric surgery for the treatment of obesity, lifestyle interventions (diet and physical activity) remain the first-line therapy for this disease. The use of digital devices in healthcare aims to respond to the patient's needs, in order to make obesity treatment more accessible, so our study aims to assess the safety and efficacy of a Digital Therapy for Obesity App (DTxO) for achieving weight loss and its maintenance in patients affected with obesity undergoing an experimental non-pharmacological treatment. Here we present the study protocol of a prospective, multicenter, pragmatic, randomized, double-arm, placebo-controlled, parallel, single-blind study on obese patients who will be treated with a new digital therapy to obtain an improvement in their disease condition through the application of different simultaneous strategies (a dietary regimen and personalized advice program, a tailored physical exercise program, a cognitive–behavioural assessment and program, alerts and reminders, dedicated section on prescribed drugs intake, and chat and online visits with clinical professionals). We believe that DTxO will offer a promising intervention channel and self-regulation tool holding the potentiality to decrease treatment burden and treat more patients thanks to the partial replacement of traditional medical consultation with digital or telephone management, improving self- engagement and reducing the high demands the “obesity pandemic” for both patients and national health services in terms of time, cost, and effort. Clinical trial registration: clinicaltrials.gov, identifier, NCT05394779.

Comfort Therapy with Companionship Improves Learning Memory and Reduces Hyperalgesia in Sickle Mice

Chronic and unpredictable acute pain coexist with cognitive dysfunction in sickle cell disease (SCD). Managing chronic pain is crucial, though efforts are complicated by both physiological and affective contributors to pain. The affective state, which is severely impacted by the environment including stigma and social isolation, plays a substantial role in pain perception and may further exacerbate psychological factors. Therefore, we examined if companionship and social isolation influence cognitive function and pain in SCD. In the present study, we examined the effects of social isolation on hyperalgesia, learning memory, and anxiety in humanized transgenic homozygous BERK mouse model of SCD. At ~3.5 months of age, BERK male mice were paired with age-matched female BERK companions (1 male + 1 female/cage; called companion group) and another group of BERK males were placed into isolation (one male/cage; called isolation group) for ~14 months. Isolation and companion groups were maintained in general housing conditions in the same room. Both groups were assessed for body weight, hyperalgesia and cognitive behaviors. Mechanical hyperalgesia was assessed by counting paw withdrawal frequency (PWF) following 10 applications of a 1.0 g von Frey monofilament (Semmes Weinstein, Stoelting, Wood Dale, IL, USA) to the plantar surface of the hind paw. Cold hyperalgesia was assessed following placement of mice onto a 4°C cold plate chamber (Stoelting) and by measuring PWF over a 2-minute period. Musculoskeletal hyperalgesia was measured by testing grip force of each mouse's peak forepaw grip to a computerized grip force meter (SA Maier, Milwaukee, WI, USA) and normalizing by body weight. The cognitive behavioral assessment consisted of an open field test to assess anxiety-related behaviors, which measured time spent and number of crosses through a central region. Working memory was assessed using novel object recognition and novel placement recognition tests to measure discrimination of novel objects and location. Data are shown as mean ± SEM and comparisons between companionship and isolation groups were performed using unpaired, two-tailed T-tests to determine statistical significance (P&amp;lt;0.05) We observed a significant increase in the body weights of males housed with females ( Companion group) compared to males in isolation (p&amp;lt;0.05). It is likely that males living with a companion were eating more compared to those under isolation. Isolated male sickle mice experience greater hyperalgesia than male mice housed with a female companion. Isolation induces greater PWF to mechanical (P&amp;lt;0.05) and cold (P&amp;lt;0.005) stimuli, indicating exacerbated hypersensitivity to mechanical and cold stimuli. Spontaneous, non-evoked musculoskeletal hyperalgesia was not significantly altered by isolation (P&amp;gt;0.05). Isolation also appeared to impact working and learning memory. Novel object recognition and novel object placement tests revealed reduced discrimination ratios in isolated mice (~25%, P&amp;lt;0.05 and ~25%, P&amp;lt;0.05), which are suggestive of impaired learning and memory function compared to mice with companionship. Open field test showed no significant difference (P&amp;gt;0.05) between isolation and companionship groups in time spent and number of crosses in the open field center area, indicating no detectable differences in anxiety-like behaviors. According to cognitive tests, mice in companionship showed greater novel object and place detection and greater cognitive ability compared to those in isolation. For the first time we show the causal role of social isolation on hyperalgesia and memory in a humanized mouse model of SCD. “ Comfort therapy” with companionship can ameliorate the perception of pain through the higher brain centres. It is also likely that mice in companionship eat more as evinced by a significant increase in their weight, which may provide additional comfort and meet the increased nutritional/calorie demands of SCD due to altered metabolism. Our observations suggest that “ comfort therapy” with improved living conditions and reducing isolation and loneliness may improve pain-related outcomes in SCD.

Psychopathological factors and personality dimensions on dysfunctional eating behaviors in a sample of individuals with obesity.

Obesity and eating disorders are considered to be part of a broad spectrum of disorders associated with weight issues and maladaptive eating styles. Several studies show that psychopathological and personality characteristics contribute to the development and maintenance of obesity and dysfunctional eating behaviors, showing a bidirectional relationship. The purpose of this study was to understand the role of psychopathological factors and personality dimensions on dysfunctional eating behaviors in a sample of individuals with obesity. The study was conducted with 96 individuals with obesity (31 males and 65 females) who underwent psychological assessment. The instruments administered included the Cognitive Behavioral Assessment 2.0 - Primary Scales, the Minnesota Multiphasic Personality Inventory-2, and the Eating Disorder Inventory. Relationships between dysfunctional eating behaviors and personality and psychopathological factors were explored through mediation analysis. Our results showed that difficulties related to impulse control and behavior, along with negative and dysphoric emotions, may be associated with difficulties in eating behavior. Mediation analysis showed that the combination of depressive and obsessive-compulsive symptomatology may exacerbate or contribute to the occurrence of eating disorders. These psychopathological aspects should be taken into account during the assessment of patients who decide to undergo bariatric surgery and should be targets of specific psychological interventions.

Milnacipran Ameliorates Executive Function Impairments following Frontal Lobe Traumatic Brain Injury in Male Rats: A Multimodal Behavioral Assessment.

Traumatic brain injuries (TBIs) affect more than 10 million patients annually worldwide, causing long-term cognitive and psychosocial impairments. Frontal lobe TBIs commonly impair executive function, but laboratory models typically focus primarily on spatial learning and declarative memory. We implemented a multi-modal approach for clinically relevant cognitive-behavioral assessments of frontal lobe function in rats with TBI and assessed treatment benefits of the serotonin-norepinephrine reuptake inhibitor, milnacipran (MLN). Two attentional set-shifting tasks (AST) evaluated cognitive flexibility via the rats' ability to locate food-based rewards by learning, unlearning, and relearning sequential rule sets with shifting salient cues. Adult male rats reached stable pre-injury operant AST (oAST) performance in 3-4 weeks, then were isoflurane-anesthetized, subjected to a unilateral frontal lobe controlled cortical impact (2.4 mm depth, 4 m/sec velocity) or Sham injury, and randomized to treatment conditions. Milnacipran (30 mg/kg/day) or vehicle (VEH; 10% ethanol in saline) was administered intraperitoneally via implanted osmotic minipumps (continuous infusions post-surgery, 60 μL/h). Rats had a 10-day recovery post-TBI/Sham before performing light/location-based oAST for 10 days and, subsequently, odor/media-based digging AST (dAST) on the last test day (26-27 days post-injury) before sacrifice. Both AST tests revealed significant deficits in TBI+VEH rats, seen as elevated total trials and errors (p < 0.05), which generally normalized in MLN-treated rats (p < 0.05). This first simultaneous dual AST assessment demonstrates oAST and dAST are sufficiently sensitive and robust to detect subtle attentional and cognitive flexibility executive impairments after frontal lobe TBI in rats. Chronic MLN administration shows promise for attenuation of post-TBI executive function deficits, thus meriting further investigation.

Diagnosis of frontotemporal dementia: recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology.

"Frontotemporal dementia" (FTD) is a clinical syndrome characterized by the focal involvement of the frontal and/or temporal lobes. FTD has three clinical phenotypes: the behavioral variant and two linguistic subtypes, namely, non-fluent/agrammatic primary progressive aphasia (PPA-NF/A) and semantic PPA (PPA-S). FTD is the second most common cause of dementia in individuals under the age of 65 years. This article presents recommendations for the diagnosis of FTD in the Brazilian scenario, considering the three levels of complexity of the health system: primary health care, secondary and tertiary levels. Diagnostic guidelines are proposed, including cognitive testing, behavioral and language assessments, laboratory tests, and neuroimaging.

Diagnóstico da demência frontotemporal: recomendações do Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia

ABSTRACT “Frontotemporal dementia” (FTD) is a clinical syndrome characterized by the focal involvement of the frontal and/or temporal lobes. FTD has three clinical phenotypes: the behavioral variant and two linguistic subtypes, namely, non-fluent/agrammatic primary progressive aphasia (PPA-NF/A) and semantic PPA (PPA-S). FTD is the second most common cause of dementia in individuals under the age of 65 years. This article presents recommendations for the diagnosis of FTD in the Brazilian scenario, considering the three levels of complexity of the health system: primary health care, secondary and tertiary levels. Diagnostic guidelines are proposed, including cognitive testing, behavioral and language assessments, laboratory tests, and neuroimaging.

Insomnia in times of COVID-19: guidelines for Cognitive-Behavioral Assessment and Intervention

The confinement derived from the health contingency due to COVID 19 has brought with it an increase in psychological disorders such as stress, anxiety and insomnia. Despite the existence of action guidelines for each of the conditions, the presence of constant environmental factors does not allow a convenient evaluation and intervention. That is why this article aims to provide guidelines for evaluation and action from an ideographic perspective. The cognitive-behavioral techniques with more evidence are analyzed and a guide to evaluation instruments adapted to the Mexican context is provided. Finally, the emphasis is placed on the importance of individual analysis in the context of confinement for the adequate choice of intervention techniques.

Advances in digital CBT: where are we now, and where next?

Digital CBT refers to the use of digital tools, platforms or devices to deliver or enhance cognitive behavioural therapy assessment, formulation, treatment, training and supervision. The 'Advances in Digital CBT' special issue aimed to document examples of innovative digital CBT practice in this rapidly developing field. In this paper, we have briefly summarised and synthesised the advances demonstrated in this group of articles. These include developments in our understanding of mental health apps, the use of digital tools as an adjunct to therapy, the effectiveness of remotely delivered CBT in routine clinical practice, our understanding of user experiences and involvement, and in digital CBT research methods. We consider the extent of current knowledge in these areas and identify where gaps in evidence lie and how the field could be taken forward to address these. Lastly, we reflect on the broader digital CBT picture and offer our suggestions of six key directions for future research: using robust study designs to evaluate and optimise digital tools; translating and culturally adapting digital tools and practices; understanding and addressing digital exclusion; exploring, reporting and addressing possible negative effects; improving user involvement in design and evaluation; and addressing the implementation gap for digital tools. We suggest that further advances in these areas would be of particular benefit to the digital CBT field.

Analysis of cognitive ability and adaptive behavior assessment tools used in an observational study of patients with mucopolysaccharidosis II

BackgroundMucopolysaccharidosis II (MPS II) is a rare lysosomal storage disease characterized by cognitive impairment in most patients. This post hoc analysis evaluated changes in cognitive function, adaptive behavior and functional outcomes in patients with neuronopathic MPS II over time. Fifty-five children with MPS II were enrolled in a 24-month observational study (NCT01822184). The Differential Ability Scales, second edition (DAS-II; early years battery for ages 2 years 6 months to 6 years 11 months, school age battery for ages 7 years to 17 years 11 months), Vineland Adaptive Behavior Scales, second edition (VABS-II) and the Hunter Syndrome-Functional Outcomes for Clinical Understanding Scale (HS-FOCUS) were performed at baseline and 3-month intervals over 2 years. A subgroup of 38 children with a DAS-II General Conceptual Ability (GCA) score of 55–85 (below average–very low abilities) at any time during the study were included in this analysis.ResultsMean (standard deviation [SD]) early years DAS-II GCA score decreased from 73.4 (15.7, n = 22) at baseline to 62.7 (34.9, n = 6) at month 24. For the six patients with early years GCA assessments at baseline and month 24, mean (SD) GCA scores decreased from 72.3 (21.3) at baseline to 62.7 (34.9) at month 24. School age GCA scores were stable over 2 years: mean (SD) 72.4 (11.8, n = 10) at baseline; 74.3 (12.3, n = 8) at month 24. Mean (SD) VABS-II Adaptive Behavior Composite (ABC) scores were stable throughout the study (baseline, 81.8 [11.8, n = 36]; month 24, 81.0 [10.2, n = 13]). Some associations between items and domains of HS-FOCUS (p < 0.05) and DAS-II GCA and VABS-II ABC scores were shown, but there was no clear pattern of changes in HS-FOCUS over 2 years.ConclusionsThe DAS-II measured changes in cognitive function over 2 years in younger patients with MPS II, whereas cognitive function in older patients remained stable. Further research is required to confirm the content validity of the DAS-II in different patient populations with MPS II. The VABS-II and HS-FOCUS were not sensitive tools for measuring behavioral and functional changes over 2 years. These findings may inform selection of appropriate cognitive and behavioral assessment tools for future studies.

Mobile Phone Addiction and Mobile Phone Use in Dangerous Circumstances: Prevalence and Correlates in a Sample of Italian University Students

Background: Beyond unambiguous advantages of mobile phones (MP), growing evidences document its problematic use and association with mental health issues. Unintentional injuries, such as road traffic or pedestrian accidents, result from dangerous use of the MP (DUMP). The aim of our study was to estimate the prevalence of DUMP and the addiction to MP in young while driving, cycling or walking (defined as DUMP) relating to some demographic and psychological factors. Methods: A cross-sectional prevalence study was carried out on a sample of 1130 Italian university students. The use and addiction to MP were studied with Italian version of the Mobile Phone Use Questionnaire (MPUQ) and Dependence test of MP (DTMP). The Cognitive Behavioral Assessment 2.0 (CBA 2.0) was used to investigate anxiety and obsessive-compulsive disorder. Results: Result statistics showed a continuous use of MP. One third of subjects showed MP addiction, associated to female and younger students. Two thirds showed risk of DUMP, associated to male and older. The obsessive-compulsive disorder was estimated only in a small fraction and significantly correlated with DTMP. Conclusions: Our study points out the importance that information and prevention campaigns targeting specific demographic subpopulations should be sought to raise young awareness for a safe use of MP.

The role of impulsivity in neurorehabilitation: A prospective cohort study of a potential cognitive biomarker for fall risk?

Executive dysregulation and impulsivity can both predispose individuals to risk-prone actions. Although the risk of falls is well established in people with poor executive function, its association to impulsivity is less clear. To describe and assess the prognostic capabilities of the relationship between impulsivity, executive function, functional capability, and falls in the in-patient neurorehabilitation population. A prospective cohort study in a 26-bed neurorehabilitation unit in London, recruiting 121 patients, of whom 94 were deemed eligible for inclusion. Cognitive-behavioural assessment was undertaken using the short (16-item) version of the Urgency-Premeditation-Perseverance-Sensation Seeking-Positive Urgency (UPPS) impulsive behaviour scale, and the Trail Making Test (TMT). Patients also underwent a functional assessment at admission and discharge using the UK Functional Independence and Assessment Measure tool (FIM+FAM). The main outcome of interest was falling during an in-patient episode, which are routinely recorded in a computerized registry of adverse incidents. Measurements of impulsivity (based on the UPPS-Short form) and executive function (based on the Trail Making Test) were not found to be significantly associated with functional improvement, or risk of falling. Predictive modelling experiments demonstrated that neither of the aforementioned results were capable of identifying individuals at risk of falling more accurately than an informed guess. Where impulsivity is present, measurement using structured tools such as the UPPS may be informative to guide individualized rehabilitation programmes; however, its usefulness as the basis of risk prediction models for falls is less likely given the results of this study.

Digital Biomarkers for the Early Detection of Mild Cognitive Impairment: Artificial Intelligence Meets Virtual Reality.

Elderly people affected by Mild Cognitive Impairment (MCI) usually report a perceived decline in cognitive functions that deeply impacts their quality of life. This subtle waning, although it cannot be diagnosable as dementia, is noted by caregivers on the basis of their relative’s behaviors. Crucially, if this condition is also not detected in time by clinicians, it can easily turn into dementia. Thus, early detection of MCI is strongly needed. Classical neuropsychological measures – underlying a categorical model of diagnosis - could be integrated with a dimensional assessment approach involving Virtual Reality (VR) and Artificial Intelligence (AI). VR can be used to create highly ecologically controlled simulations resembling the daily life contexts in which patients’ daily instrumental activities (IADL) usually take place. Clinicians can record patients’ kinematics, particularly gait, while performing IADL (Digital Biomarkers). Then, Artificial Intelligence employs Machine Learning (ML) to analyze them in combination with clinical and neuropsychological data. This integrated computational approach would enable the creation of a predictive model to identify specific patterns of cognitive and motor impairment in MCI. Therefore, this new dimensional cognitive-behavioral assessment would reveal elderly people’s neural alterations and impaired cognitive functions, typical of MCI and dementia, even in early stages for more time-sensitive interventions.

Which are the factors influencing NIV adaptation and tolerance in ALS patients?

Amyotrophic lateral sclerosis (ALS) is a multisystemic disease compromising both the neuromuscular system and the cognitive status. Non-invasive ventilation (NIV) has been shown to improve survival and quality of life in ALS patients with respiratory failure, but scanty literature investigated which are the predictors of NIV tolerance. The aim of this study was to evaluate the impact of functional, cognitive, neurobehavioral, and respiratory status on NIV compliance and tolerance in patients with ALS. We retrospectively evaluated clinical data of ALS patients who consecutively underwent a NIV trial during hospitalization. Cognitive and neurobehavioral assessments have been performed using the Edinburgh Cognitive and Behavioral ALS Screen (ECAS), the Hospital Anxiety and Depression Scale (HADS), the Frontal Assessment Battery (FAB), the Raven's 47 Colored Progressive Matrices (PM47), and the Neurobehavioral Rating Scale Revised (NRSR). Seventy-two patients (mean age ± SD; 63.9 ± 10.6 years) were included. Patients adapted were 63/72 (87.5%). The average time of adaptation was 7.82 ± 5.27 days. The time required to reach a satisfying NIV adaptation was significantly related to the presence of sialorrhea (p = 0.02), respiratory status (Borg Dyspnoea Scale, p = 0.006, and ALS-FRS-R respiratory subscore, p = 0.03) and behavioral and cognitive impairment (NRSR-F1, p = 0.04, NRSR- F5, p = 0.04). Presence of sialorrhea and neurobehavioral impairment, and absence of respiratory symptoms are negative predictors of NIV adaptation. This study highlights the need of a multidisciplinary patient-tailored approach including cognitive-behavioral assessment and a psychological support program to optimize patient's training and compliance to NIV.

Dyslexia in Pediatrics: Simple Practices to Tackle a Complex Issue.

* Abbreviation: SLD — : specific learning disorder It is not uncommon for children with specific learning disorders (SLDs) to go through several years of school without receiving necessary academic support, emphasizing the need for earlier detection. Precursor skills of learning often provide important, early indications about whether a child might be at risk for developing an SLD. In this issue of Pediatrics, Sanfilippo et al1 provide a timely overview of current evidence on precursors of reading and outline how pediatricians can contribute to early identification of children at risk for dyslexia. Sanfilippo et al1 highlight “red flags” that can assist pediatricians in identifying dyslexia, including screening for family history, language development, and early literacy skills. Screening may be composed of cognitive-behavioral assessments that typically focus on phonological awareness, basic letter knowledge, vocabulary size, and language comprehension. Given that SLDs are of neurobiological origin, neuroimaging techniques have been used to investigate neural signatures of these precursor skills.2 Increasing evidence suggests that neurobiological markers can predict individual reading outcomes, outperforming the prediction accuracy of cognitive-behavioral precursors of literacy.3,4 As the authors point out, neuroimaging screenings are not (yet) available, … Address correspondence to Iliana I. Karipidis, PhD, Department of Psychiatry and Behavioral Sciences, Stanford Medicine, Stanford University, 401 Quarry Rd, Stanford, CA 94305, E-mail: ilianak{at}stanford.edu

Novel neuroprotection using antioxidant nanoparticles in a mouse model of head trauma.

Free radicals and reactive oxygen species are related to deteriorating pathological conditions after head trauma because of their secondary effects. 2,2,6,6-Tetramethylpiperidine-1-oxyl (TEMPO) scavenges free radicals; however, this molecule is also toxic. Here, we have evaluated the neuroprotective effect of antioxidant nanoparticles, which consisted of a novel core-shell type nanoparticle containing 4-amino-TEMPO, that is, redox-active nitroxide radical-containing nanoparticles (RNPs). Institute of Cancer Research mice were subjected to a head-impact procedure, randomly divided into four groups and intravenously (3 mg/kg) administered phosphate-buffered saline, TEMPO, micelle (a self-assembling block copolymer micelle without a TEMPO moiety), or RNP through the tail vein immediately thereafter and intraperitoneally at days 1, 3, and 5 after traumatic brain injury (TBI). The RNP distribution was detected by rhodamine labeling. Cognitive behavior was assessed using the neurological severity score and a rotarod test at days 1, 3, and 7 following TBI, and contusion volume was measured at day 7 after TBI. Free radical-scavenging capacity was analyzed by electron paramagnetic resonance on day 1 after TBI, and immunostaining was used to observe mobilization of microglia (Iba-1) and rescued neuronal cells (NeuN). Redox-active nitroxide radical-containing nanoparticle was detected in the microvessels around the injured area in the brain. Cognitive behavior assessment was significantly better, and contusion volume was significantly smaller in the RNP group compared with the other groups. Superoxide anion scavenging capacity was significantly higher in the RNP group, and neuronal loss was significantly suppressed around the injured area at day 7 after TBI. Furthermore, in the RNP group, neurodegenerative microglia production was suppressed at days 3 and 7 after TBI, whereas neuroprotective microglia production was higher at day 7 after TBI. The RNP administration after TBI improved cognitive behavior and reduced contusion volume by improving reactive oxygen species scavenging capacity. Therefore, RNP may have a neuroprotective effect after TBI. Therapeutic test.