Allostatic load, adverse childhood experiences, executive functions, and BMI status in adolescents and young adults.

OBJECTIVES: Chronic stress induces preclinical changes in the metabolic, cardiovascular, and immune systems. This phenomenon, known as allostatic load (AL), can impair executive functions (EF), which may be even more affected in individuals with excess weight due to their characteristic inflammatory state and cardiometabolic changes. Adverse childhood experiences (ACEs) contribute to AL and may influence executive functioning presumably via alterations within the hypothalamic-pituitary axis, including epigenetic modifications. We assess the relationship between AL and EF in youth with and without excess weight, and the effect ACEs on executive functioning. METHODS: One hundred eighty-two adolescents and young adults (85 with normal weight and 97 with overweight/obesity; 10-21 years) were recruited. The estimated AL index included the following: systolic and diastolic blood pressure, glycated hemoglobin, high- and low-density lipoprotein cholesterol, triglycerides, high-sensitivity C-reactive protein, fibrinogen, and cortisol. ACEs were measured using the Juvenile Victimization Questionnaire. The neuropsychological evaluation included the assessment of inhibition, working memory, and cognitive flexibility processes. RESULTS: AL was not significantly associated with executive functioning, and this relationship did not depend on body-weight status. ACEs, available for 57 of 182 participants, were significantly associated with poorer executive functioning. CONCLUSIONS: Our study shows that AL is not associated with executive functioning in adolescents and young adults. Since the current sample was young, we hypothesize that a longer exposure to AL might be required for its negative effects to surface. Nevertheless, exposure to early adversity seems to be associated with poorer executive functioning in youth.

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.

From the reward network to whole-brain metrics: structural connectivity in adolescents and young adults according to body mass index and genetic risk of obesity.

BACKGROUND: Obesity is a multifactorial condition. Genetic variants, such as the fat mass and obesity related gene (FTO) polymorphism, may increase the vulnerability of developing obesity by disrupting dopamine signaling within the reward network. Yet, the association of obesity, genetic risk of obesity, and structural connectivity of the reward network in adolescents and young adults remains unexplored. We investigate, in adolescents and young adults, the structural connectivity differences in the reward network and at the whole-brain level according to body mass index (BMI) and the FTO rs9939609 polymorphism. METHODS: One hundred thirty-two adolescents and young adults (age range: [10, 21] years, BMI z-score range: [-1.76, 2.69]) were included. Genetic risk of obesity was determined by the presence of the FTO A allele. Whole-brain and reward network structural connectivity were analyzed using graph metrics. Hierarchical linear regression was applied to test the association between BMI-z, genetic risk of obesity, and structural connectivity. RESULTS: Higher BMI-z was associated with higher (B = 0.76, 95% CI = [0.30, 1.21], P = 0.0015) and lower (B = -0.003, 95% CI = [-0.006, -0.00005], P = 0.048) connectivity strength for fractional anisotropy at the whole-brain level and of the reward network, respectively. The FTO polymorphism was not associated with structural connectivity nor with BMI-z. CONCLUSIONS: We provide evidence that, in healthy adolescents and young adults, higher BMI-z is associated with higher connectivity at the whole-brain level and lower connectivity of the reward network. We did not find the FTO polymorphism to correlate with structural connectivity. Future longitudinal studies with larger sample sizes are needed to assess how genetic determinants of obesity change brain structural connectivity and behavior.

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.

Body mass index, systemic inflammation and cognitive performance in adolescents: A cross-sectional study.

BACKGROUND: Excessive body weight has been related to lower cognitive performance. One of the mechanisms through which excess body weight may affect cognition is inflammation. HYPOTHESIS: Our hypothesis is that both body mass index (BMI) and circulating levels of inflammatory biomarkers will be negatively related to cognitive performance. DESIGN: Cross-sectional study. SETTING: Users of the public health centres of the Consorci Sanitari de Terrassa (Terrassa, Spain) between 2010 and 2017 aged 12-21 years. PARTICIPANTS: One hundred and five adolescents (46 normoweight, 18 overweight, 41 obese). MEASUREMENTS: Levels of high sensitivity C-reactive protein, interleukin 6, tumour necrosis factor α (TNFα) and fibrinogen were determined from blood samples. Cognitive performance was evaluated and six cognitive composites were obtained: working memory, cognitive flexibility, inhibitory control, decision-making, verbal memory, and fine motor speed. A single multivariate general lineal model was used to assess the influence of the four inflammatory biomarkers, as well as participants' BMI, sex, and age on the 6 cognitive indexes. RESULTS: An inverse relationship between BMI and inhibitory control (F = 5.688, p = .019; ß = -0.212, p = .031), verbal memory (F = 5.404, p = .022; ß = -0.255, p = .009) and fine motor speed (F = 9.038, p = .003; ß = -0.319, p = .001) was observed. Levels of TNFα and fibrinogen were inversely related to inhibitory control (F = 5.055, p = .027; ß = -0.226, p = .021) and verbal memory (F = 4.732, p = .032; ß = -0.274, p = .005), respectively. LIMITATIONS: The cross-sectional nature of the study, the use of cognitive tests designed for clinical purposes, and the use of BMI as a proxy for adiposity are limitations of our study that must be taken into account when interpreting results. CONCLUSIONS: Our data indicate that some components of executive functions, together with verbal memory, are sensitive to specific obesity-related inflammatory agents at early ages.

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.

Beyond BMI: cardiometabolic measures as predictors of impulsivity and white matter changes in adolescents.

Obesity is characterized by cardiometabolic and neurocognitive changes. However, how these two factors relate to each other in this population is unknown. We tested the association that cardiometabolic measures may have with impulse behaviors and white matter microstructure in adolescents with and without an excess weight. One hundred and eight adolescents (43 normal-weight and 65 overweight/obesity; 11-19 years old) were medically and psychologically (Temperament Character Inventory Revised, Three-Factor Eating Questionnaire-R18, Conners' Continuous Performance Test-II, Stroop Color and Word Test, Wisconsin Card Sorting Test, Kirby Delay Discounting Task) evaluated. A subsample of participants (n = 56) underwent a brain magnetic resonance imaging acquisition. In adolescents, higher triglycerides and having a body mass index indicative of overweight/obesity predicted a more impulsive performance in Conners' Continuous Performance Test-II (higher commission errors). In addition, higher glucose and diastolic blood pressure values predicted increments in the Three-Factor Eating Questionnaire-R18 emotional eating scale. Neuroanatomically, cingulum fractional anisotropy showed a negative relationship with glycated hemoglobin. The evaluation of the neurocognitive differences associated with obesity, usually based on body mass index, should be complemented with cardiometabolic measures.

Influence of Executive Function Training on BMI, Food Choice, and Cognition in Children with Obesity: Results from the TOuCH Study.

BACKGROUND: Children with obesity have a higher risk of future health and psychological problems. Executive functions (EFs) play a key role in successful dietetic and exercise planning; therefore, new treatments aimed at improving EFs may optimize outcomes. OBJECTIVES: This study evaluates the impact of EF training on body mass index (BMI), food choice, and cognition in children with obesity. We also examine their real-life executive functioning, emotional state, and quality of life. METHODS: Randomized controlled double-blind trial. Forty-six children with obesity were randomly allocated into an executive functions training or a control task training group and attended 30-45 min of daily training (5/week over 6 weeks), with both groups receiving counseling on diet and wearing an activity/sleep tracker. Participants were evaluated at baseline and after treatment. RESULTS: BMI decreased over time in the whole sample, although there were no differences between groups at post-training in BMI, food choice, and cognition. Both groups showed significant improvements in attention, speed, cognitive flexibility, and inhibitory control. Additionally, there were some benefits in real-life executive functioning and self-esteem. Over the 6 weeks, participants showed worse food choices in both groups. CONCLUSIONS: EFs training showed a lack of significant effects. The executive function enhancement alone did not explain these changes, as there were no significant differences between the experimental groups. It might be that the control task training could also produce some benefits, and multi-component interventions might be useful for weight loss.

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.

The Impact of COVID-19 Confinement on Cognition and Mental Health and Technology Use Among Socially Vulnerable Older People: Retrospective Cohort Study.

BACKGROUND: COVID-19 forced the implementation of restrictive measures in Spain, such as lockdown, home confinement, social distancing, and isolation. It is necessary to study whether limited access to basic services and decreased family and social support could have deleterious effects on cognition, quality of life, and mental health in vulnerable older people. OBJECTIVE: This study aims to explore the impact of the COVID-19 outbreak on cognition in older adults with mild cognitive impairment or dementia as the main outcome and the quality of life, perceived health status, and depression as secondary outcomes and to analyze the association of living alone and a change in living arrangements with those outcomes and other variables related with the use of technology and health services. Likewise, this study aims to analyze the association of high and low technophilia with those variables, to explore the access and use of health care and social support services, and, finally, to explore the informative-, cognitive-, entertainment-, and socialization-related uses of information and communications technologies (ICTs) during the COVID-19 outbreak. METHODS: This cohort study was conducted in Málaga (Spain). In total, 151 participants with mild cognitive impairment or mild dementia, from the SMART4MD (n=75, 49.7%) and TV-AssistDem (n=76, 50.3%) randomized clinical trials, were interviewed by telephone between May 11 and June 26, 2020. All participants had undergone 1-3 assessments (in 6-month intervals) on cognition, quality of life, and mood prior to the COVID-19 breakout. RESULTS: The outbreak did not significantly impact the cognition, quality of life, and mood of our study population when making comparisons with baseline assessments prior to the outbreak. Perceived stress was reported as moderate during the outbreak. After correction for multiple comparisons, living alone, a change in living arrangements, and technophilia were not associated with negative mental health outcomes. However, being alone was nominally associated with self-perceived fear and depression, and higher technophilia with better quality of life, less boredom, perceived stress and depression, and also less calmness. Overall, health care and social support service access and utilization were high. The most used ICTs during the COVID-19 outbreak were the television for informative, cognitive, and entertainment-related uses and the smartphone for socialization. CONCLUSIONS: Our findings show that the first months of the outbreak did not significantly impact the cognition, quality of life, perceived health status, and depression of our study population when making comparisons with baseline assessments prior to the outbreak. Living alone and low technophilia require further research to establish whether they are risk factors of mental health problems during lockdowns in vulnerable populations. Moreover, although ICTs have proven to be useful for informative-, cognitive-, entertainment-, and socialization-related uses during the pandemic, more evidence is needed to support these interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT04385797; https://clinicaltrials.gov/ct2/show/NCT04385797. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/26431.

Assessment of Neurocognitive Functions, Olfaction, Taste, Mental, and Psychosocial Health in COVID-19 in Adults: Recommendations for Harmonization of Research and Implications for Clinical Practice.

OBJECTIVE: To propose a set of internationally harmonized procedures and methods for assessing neurocognitive functions, smell, taste, mental, and psychosocial health, and other factors in adults formally diagnosed with COVID-19 (confirmed as SARS-CoV-2 + WHO definition). METHODS: We formed an international and cross-disciplinary NeuroCOVID Neuropsychology Taskforce in April 2020. Seven criteria were used to guide the selection of the recommendations' methods and procedures: (i) Relevance to all COVID-19 illness stages and longitudinal study design; (ii) Standard, cross-culturally valid or widely available instruments; (iii) Coverage of both direct and indirect causes of COVID-19-associated neurological and psychiatric symptoms; (iv) Control of factors specifically pertinent to COVID-19 that may affect neuropsychological performance; (v) Flexibility of administration (telehealth, computerized, remote/online, face to face); (vi) Harmonization for facilitating international research; (vii) Ease of translation to clinical practice. RESULTS: The three proposed levels of harmonization include a screening strategy with telehealth option, a medium-size computerized assessment with an online/remote option, and a comprehensive evaluation with flexible administration. The context in which each harmonization level might be used is described. Issues of assessment timelines, guidance for home/remote assessment to support data fidelity and telehealth considerations, cross-cultural adequacy, norms, and impairment definitions are also described. CONCLUSIONS: The proposed recommendations provide rationale and methodological guidance for neuropsychological research studies and clinical assessment in adults with COVID-19. We expect that the use of the recommendations will facilitate data harmonization and global research. Research implementing the recommendations will be crucial to determine their acceptability, usability, and validity.

Preserved central nervous system functioning after use of romidepsin as a latency-reversing agent in an HIV cure strategy.

OBJECTIVE: To assess the central nervous system (CNS) impact of a kick&kill HIV cure strategy using therapeutic vaccine MVA.HIVconsv and the histone deacetylase inhibitor (HDACi) romidepsin (RMD) as latency-reversing agent. DESIGN: Neurological observational substudy of the BCN02 trial (NCT02616874), a proof-of-concept, open-label, single-arm, phase I clinical trial testing the safety and immunogenicity of the MVA.HIVconsv vaccine and RMD in early-treated HIV-1-infected individuals. A monitored antiretroviral pause (MAP) was performed, with cART resumption after 2 pVL more than 2000 copies/ml. Reinitiated participants were followed for 24 weeks. METHODS: Substudy participation was offered to all BCN02 participants (N = 15). Evaluations covered cognitive, functional, and brain imaging outcomes, performed before RMD administration (pre-RMD), after three RMD infusions (post-RMD), and at the end of the study (EoS). A group of early-treated HIV-1-infected individuals with matched clinical characteristics was additionally recruited (n = 10). Primary endpoint was change in a global cognitive score (NPZ-6). RESULTS: Eleven participants from BCN02 trial were enrolled. No significant changes were observed in cognitive, functional, or brain imaging outcomes from pre-RMD to post-RMD. No relevant alterations were detected from pre-RMD to EoS either. Scores at EoS were similar in participants off cART for 32 weeks (n = 3) and those who resumed therapy for 24 weeks (n = 7). Controls showed comparable punctuations in NPZ-6 across all timepoints. CONCLUSION: No detrimental effects on cognitive status, functional outcomes, or brain imaging parameters were observed after using the HDACi RMD as latency-reversing agent with the MVA.HIVconsv vaccine in early-treated HIV-1-infected individuals. CNS safety was also confirmed after completion of the MAP.

Restrained Eating Is Associated with Lower Cortical Thickness in the Inferior Frontal Gyrus in Adolescents.

Some eating patterns, such as restrained eating and uncontrolled eating, are risk factors for eating disorders. However, it is not yet clear whether they are associated with neurocognitive differences. In the current study, we analyzed whether eating patterns can be used to classify participants into meaningful clusters, and we examined whether there are neurocognitive differences between the clusters. Adolescents (n = 108; 12 to 17 years old) and adults (n = 175, 18 to 40 years old) completed the Three Factor Eating Questionnaire, which was used to classify participants according to their eating profile using k means clustering. Participants also completed personality questionnaires and a neuropsychological examination. A subsample of participants underwent a brain MRI acquisition. In both samples, we obtained a cluster characterized by high uncontrolled eating patterns, a cluster with high scores in restrictive eating, and a cluster with low scores in problematic eating behaviors. The clusters were equivalent with regards to personality and performance in executive functions. In adolescents, the cluster with high restrictive eating showed lower cortical thickness in the inferior frontal gyrus compared to the other two clusters. We hypothesize that this difference in cortical thickness represents an adaptive neural mechanism that facilitates inhibition processes.

Associations Between Mobile Health Technology use and Self-rated Quality of Life: A Cross-sectional Study on Older Adults with Cognitive Impairment.

Background: Quality of life (QoL) is affected even at early stages in older adults with cognitive impairment. The use of mobile health (mHealth) technology can offer support in daily life and improve the physical and mental health of older adults. However, a clarification of how mHealth technology can be used to support the QoL of older adults with cognitive impairment is needed. Objective: To investigate factors affecting mHealth technology use in relation to self-rated QoL among older adults with cognitive impairment. Methods: A cross-sectional research design was used to analyse mHealth technology use and QoL in 1,082 older participants. Baseline data were used from a multi-centered randomized controlled trial including QoL, measured by the Quality of Life in Alzheimer's Disease (QoL-AD) Scale, as the outcome variable. Data were analyzed using logistic regression models. Results: Having moderately or high technical skills in using mHealth technology and using the internet via mHealth technology on a daily or weekly basis was associated with good to excellent QoL in older adults with cognitive impairment. Conclusions: The variation in technical skills and internet use among the participants can be interpreted as an obstacle for mHealth technology to support QoL.

Effects of integrase inhibitor-based antiretroviral therapy on brain outcomes according to time since acquisition of HIV-1 infection.

Integrase strand transfer inhibitors (INSTI) are a main component of the current antiretroviral regimens recommended for treatment of HIV infection. However, little is known about the impact of INSTI on neurocognition and neuroimaging. We developed a prospective observational trial to evaluate the effects of INSTI-based antiretroviral therapy on comprehensive brain outcomes (cognitive, functional, and imaging) according to the time since HIV-1 acquisition. We recruited men living with HIV who initiated antiretroviral therapy with INSTI < 3 months since the estimated date of HIV-1 acquisition (n = 12) and > 6 months since estimated date of HIV-1 acquisition (n = 15). We also recruited a group of matched seronegative individuals (n = 15). Assessments were performed at baseline (before initiation of therapy in HIV arms) and at weeks 4 and 48. Baseline cognitive functioning was comparable between the arms. At week 48, we did not find cognitive differences between starting therapy with INSTI earlier than 3 months or later than 6 months after acquisition of HIV-1 infection. Functional status was poorer in individuals diagnosed earlier. This effect recovered 48 weeks after initiation of therapy. Regarding brain imaging, we found that men living with HIV initiating antiretroviral therapy later experienced a greater decrease in medial orbitofrontal cortex over time, with expected negative repercussions for decision-making tasks.

Alterations in Brain Network Organization in Adults With Obesity as Compared With Healthy-Weight Individuals and Seniors.

OBJECTIVE: Life expectancy and obesity rates have drastically increased in recent years. An unhealthy weight is related to long-lasting medical disorders that might compromise the normal course of aging. The aim of the current study of brain connectivity patterns was to examine whether adults with obesity would show signs of premature aging, such as lower segregation, in large-scale networks. METHODS: Participants with obesity (n = 30, mean age = 32.8 ± 5.68 years) were compared with healthy-weight controls (n = 33, mean age = 30.9 ± 6.24 years) and senior participants who were stroke-free and without dementia (n = 30, mean age = 67.1 ± 6.65 years) using resting-state magnetic resonance imaging and graph theory metrics (i.e., small-world index, clustering coefficient, characteristic path length, and degree). RESULTS: Contrary to our hypothesis, participants with obesity exhibited a higher clustering coefficient compared with senior participants (t = 5.06, p < .001, d = 1.23, 95% CIbca = 0.64 to 1.88). Participants with obesity also showed lower global degree relative to seniors (t = -2.98, p = .014, d = -0.77, 95% CIbca = -1.26 to -0.26) and healthy-weight controls (t = -2.92, p = .019, d = -0.72, 95% CIbca = -1.19 to -0.25). Regional degree alterations in this group were present in several functional networks. CONCLUSIONS: Participants with obesity displayed greater network clustering than did seniors and also had lower degree compared with seniors and individuals with normal weight, which is not consistent with the notion that obesity is associated with premature aging of the brain. Although the cross-sectional nature of the study precludes causal inference, the overly clustered network patterns in obese participants could be relevant to age-related changes in brain function because regular networks might be less resilient and metabolically inefficient.

Executive Function Training in Childhood Obesity: Food Choice, Quality of Life, and Brain Connectivity (TOuCH): A Randomized Control Trial Protocol.

Background: Individuals with obesity are known to present cognitive deficits, especially in executive functions. Executive functions play an important role in health and success throughout the whole life and have been related to food decision-making and to the ability to maintain energy balance. It is possible to improve executive functions through targeted training. This would involve brain plasticity changes that could be studied through connectivity MRI. The general hypothesis of this study is that executive functions training in children with obesity can improve food choices and produce cognitive and neuroimaging changes (structural and functional connectivity), as well as improve emotional state and quality of life. Methods: Randomized controlled double-blind trial with 12-month follow-up. Thirty children with obesity will be randomly allocated into "executive training" (Cognifit with adaptive difficulty + Cogmed) or "control task" group (Cognifit without adaptive difficulty). Both groups will attend 30-45 min of individual gamified training (Cogmed and/or Cognifit systems) by iPad, five times per week during 6 weeks. Cogmed and Cognifit software are commercially available from Pearson and Cognifit, respectively. Participants will receive an iPad with both apps installed for a 6-week use. Participants will also receive counseling diet information via presentations sent to the iPad and will wear a Fitbit Flex 2 tracker to monitor daily activity and sleep patterns. Main outcomes will be cognitive, emotional, food decision, and quality-of-life measures, as well as neuroimaging measures. Participants are evaluated at baseline (T0), after treatment (T1), and 12 months since baseline (T2). Discussion: Longitudinal study with active control group and 3 time points: baseline, immediately after treatment, and 1 year after baseline. Threefold treatment: executive function training, psychoeducation, and feedback on activity/sleep tracking. We will evaluate the transfer effects of the intervention, including emotional and functional outcomes, as well as the effects on neural plasticity by connectivity MRI. Trial registration: This project has been registered in ClinicalTrials.gov (trial registration number NCT03615274), August 3, 2018.

Feasibility-Usability Study of a Tablet App Adapted Specifically for Persons with Cognitive Impairment-SMART4MD (Support Monitoring and Reminder Technology for Mild Dementia).

Population ageing within Europe has major social and economic consequences. One of the most devastating conditions that predominantly affects older people is dementia. The SMART4MD (Support Monitoring and Reminder Technology for Mild Dementia) project aims to develop and test a health application specifically designed for people with mild dementia. The aim of this feasibility study was to evaluate the design of the SMART4MD protocol, including recruitment, screening, baseline examination and data management, and to test the SMART4MD application for functionality and usability before utilization in a full-scale study. The feasibility study tested the protocol and the app in Spain and Sweden. A total of nineteen persons with cognitive impairment, and their informal caregivers, individually performed a task-based usability test of the SMART4MD app model in a clinical environment, followed by four-week testing of the app in the home environment. By employing a user-centered design approach, the SMART4MD application proved to be an adequate and feasible interface for an eHealth intervention. In the final usability test, a score of 81% satisfied users was obtained. The possibility to test the application in all the procedures included in the study generated important information on how to present the technology to the users and how to improve these procedures.