General Cognition Research Articles

Type II diabetes and cognitive function among older adults in India and China—results from Harmonized Cognitive Assessment Protocol studies

ObjectiveType II diabetes is a recognized risk factor of declining cognitive function in high-income countries. However, there is limited research on this association across low- and middle-income countries. We aimed to examine and compare the relationship between type II diabetes and cognition amongst adults aged 60 years and older for two of the largest LMICs: India and China.MethodsCross-sectional data was analyzed from population-based Harmonized Cognitive Assessment Protocols studies in India (n = 4,062) and China (n = 9,741). Multivariable-adjusted linear regression models examined the relationship between diabetes (self-reported or biomarker HbA1c ≥6.5%) and general cognition. Interaction testing assessed effect modification based on urban versus rural residence and educational attainment.ResultsType II diabetes was not associated with general cognitive scores in India or China in fully adjusted models. Interaction testing revealed a positive association in rural but not urban residences in India, however this was not seen in China. Both countries showed effect modification by education attainment. In India, diabetes was associated with higher average cognitive scores among those with none or early childhood education, while the relationship was null among those with at least an upper secondary education. In China, diabetes was inversely related to average cognitive scores among those with less than lower secondary education, while the relationship was null among the remainder of the study sample.ConclusionThe type II diabetes and cognitive function association in India and China differs from that observed in high-income countries. These findings suggest epidemiologic and nutrition transition variations. In India, health care access, urbanization and social differences between urban and rural areas may influence this relationship. In both countries, epidemiologic and nutrition patterns may adversely impact individuals from socially and financially vulnerable populations with less than lower secondary education. Longitudinal research using harmonized cognitive scores is encouraged to further investigate these findings.

Organizational and legal principles of forensic examination in the field of road infrastructure

The aim of the work is to analyze the offenses committed in the field of road infrastructure and to identify the main areas of criminal activity, for which investigation specific expertise in the form of forensic examination is applied. The methodological basis of the study of this problem was general, separate and special cognition methods. The results of performed research demonstrate possibility of distinguishing two main areas of criminal activity in the field of road infrastructure. These are official crimes related to the field of official and professional activity, as well as war crimes related to unforeseen destruction of road infrastructure. Thus, one of socially dangerous manifestations in this area are crimes related to road construction. While investigating issues of compliance of the developed project-technical and estimate documentation with the requirements of regulatory acts in the field of road construction, as well as questions of determining compliance of the completed construction works and built objects with the project-technical documentation, often arise. Such issues can be resolved if forensic expert (experts) have relevant professional knowledge in the design, construction and operation of roads, taking into account the characteristics of road infrastructure objects. At the current stage, when all Ukrainians feel consequences of Russian aggression, another problem is clearly visible. After all, for all the crimes of this shameful war, the enemy must suffer a just punishment, and the victims must receive compensation for the material and moral damage caused to them. In connection with the emergence of new tasks that arise during the investigation of war crimes committed by the aggressor country, the question of the appropriate level of expert provision of justice in conditions of war that is directly related both to increasing effectiveness of the inspection of the scene of the event and to further conducting forensic examinations. Taking into account the fact that a huge number of objects were damaged and destroyed, there was a need to use the latest methods and approaches to effectively counteract the specified manifestations of crime, in particular, development of effective system of expert justice provision at the stages of pre-trial investigation and subsequent judicial review of cases. Thereby it is important to provide expert investigation of crimes related to the establishment of damages to the state, individuals and legal entities from the destruction of immovable and movable property.

Systolic blood pressure variability in late-life predicts cognitive trajectory and risk of Alzheimer's disease.

The relationship of systolic blood pressure variability (SBPV) with Alzheimer's disease (AD) remains controversial. We aimed to explore the roles of SBPV in predicting AD incidence and to test the pathways that mediated the relationship of SBPV with cognitive functions. Longitudinal data across 96 months (T0 to T4) were derived from the Alzheimer's disease Neuroimaging Initiative cohort. SBPV for each participant was calculated based on the four measurements of SBP across 24 months (T0 to T3). At T3, logistic regression models were used to test the SBPV difference between 86 new-onset AD and 743 controls. Linear regression models were used to test the associations of SBPV with cognition and AD imaging endophenotypes for 743 non-demented participants (median age = 77.0, female = 42%). Causal mediation analyses were conducted to explore the effects of imaging endophenotypes in mediating the relationships of SBPV with cognitive function. Finally, Cox proportional hazard model was utilized to explore the association of SBPV with incident risk of AD (T3 to T4, mean follow-up = 3.5 years). Participants with new-onset AD at T3 had significantly higher SBPV compared to their controls (p = 0.018). Higher SBPV was associated with lower scores of cognitive function (p = 0.005 for general cognition, p = 0.029 for memory, and p = 0.016 for executive function), higher cerebral burden of amyloid deposition by AV45 PET (p = 0.044), lower brain metabolism by FDG PET (p = 0.052), and higher burden of white matter hyperintensities (WMH) (p = 0.012). Amyloid pathology, brain metabolism, and WMH partially (ranging from 17.44% to 36.10%) mediated the associations of SBPV with cognition. Higher SBPV was significantly associated with elevated risk of developing AD (hazard ratio = 1.29, 95% confidence interval = 1.07 to 1.57, p = 0.008). These findings supported that maintaining stable SBP in late life helped lower the risk of AD, partially by modulating amyloid pathology, cerebral metabolism, and cerebrovascular health.

Cognitive impairment mediates the white matter injury load and gait disorders in subcortical ischemic vascular disease.

Gait disorders are common in patients with subcortical ischemic vascular disease (SIVD). We aim to explore the impact of white matter (WM) damage on gait disorders in SIVD. 21 SIVD patients and 20 normal controls (NC) were included in the study. Montreal Cognitive Assessment (MoCA) was used to evaluate general cognition, while Speed-Accuracy Trade-Off (SAT) was used to assess executive function. Gait velocity, cadence, and stride length were measured. Diffusion Tensor Imaging (DTI) data were analyzed using Tract-Based Spatial Statistics (TBSS) and Peak Width of Skeletonized Mean Diffusivity (PSMD). The relationships among WM damage, gait disorders, and cognitive function were examined through mediation analysis. SIVD scored lower than NC in MoCA and SAT tests (P < 0.001). Gait velocity and stride length were decreased in SIVD. SIVD had lower PSMD (P < 0.001). PSMD correlated with gait parameters, which were totally mediated by MoCA and partially mediated by SAT. The fractional anisotropy (FA) and mean diffusivity (MD) of the genu of the corpus callosum (GCC) and body of CC (BCC) were correlated with gait parameters. The FA of the bilateral anterior corona radiata (ACR) was positively correlated with gait parameters, while the MD of the bilateral superior corona radiata (SCR), bilateral superior longitudinal fasciculus (SLF), and left external capsule (EC) were negatively correlated with them (P < 0.05). Gait impairments in SIVD were associated with cognitive deficits. Cognitive impairment mediated the WM damage and gait disorders. The microstructural alterations of CC, SLF, EC, and CR may be related to changes in gait.

Identification of novel genetic loci related to dromedary camel (Camelus dromedarius) morphometrics, biomechanics, and behavior by genome-wide association studies

In the realm of animal breeding for sustainability, domestic camels have traditionally been valued for their milk and meat production. However, key aspects such as zoometrics, biomechanics, and behavior have often been overlooked in terms of their genetic foundations. Recognizing this gap, the present study perfomed genome-wide association analyses to identify genetic markers associated with zoometrics-, biomechanics-, and behavior-related traits in dromedary camels (Camelus dromedarius). 16 and 108 genetic markers were significantly associated (q < 0.05) at genome and chromosome-wide levels of significance, respectively, with zoometrics- (width, length, and perimeter/girth), biomechanics- (acceleration, displacement, spatial position, and velocity), and behavior-related traits (general cognition, intelligence, and Intelligence Quotient (IQ)) in dromedaries. In most association loci, the nearest protein-coding genes are linkedto neurodevelopmental and sensory disorders. This suggests that genetic variations related to neural development and sensory perception play crucial roles in shaping a dromedary camel’s physical characteristics and behavior. In summary, this research advances our understanding of the genomic basis of essential traits in dromedary camels. Identifying specific genetic markers associated with zoometrics, biomechanics, and behavior provides valuable insights into camel domestication. Moreover, the links between these traits and genes related to neurodevelopmental and sensory disorders highlight the broader implications of domestication and modern selection on the health and welfare of dromedary camels. This knowledge could guide future breeding strategies, fostering a more holistic approach to camel husbandry and ensuring the sustainability of these animals in diverse agricultural contexts.

Cognitive reserve as residual variance in cognitive performance: Latent dimensionality, correlates, and dementia prediction.

Cognitive reserve (CR) is typically operationalized as episodic memory residualized on brain health indices. The dimensionality of more generalized models of CR has rarely been examined. In a sample of N = 113 dementia-free older adults (ages 62-86 years at MRI scan; 58.4% women), the domain-specific representation of general cognition (COG) before vs. after residualization on brain indices (brain volume loss, cerebral blood flow, white matter hyperintensities) was compared (i.e., COG vs. CR). COG and CR were assessed by 15 tasks spanning five domains: processing speed, verbal memory, visuospatial memory, fluid reasoning, and vocabulary. Measurement invariance and item-construct representation were tested in a series of structural factor analyses. COG and CR were then examined in relation to 22 risk and protective factors and dementia status at time of death. Item-factor loadings differed such that CR more strongly emphasized fluid reasoning. More years of education, higher occupational class, more hobbies/interests, and fewer difficulties with personal mobility similarly predicted better COG and CR. Only the sub-domain of visuospatial memory (both before and after residualization) was associated with conversion to dementia by end-of-life (r = -.30; p = .01). Results provide tentative support for the role of fluid reasoning (intelligence) as a potential compensatory factor for age- and/or neuropathology-related reductions in processing speed and memory. Intellectually stimulating work, efforts to preserve personal mobility, and a diversity of hobbies and interests may attenuate age- and/or pathology-related reductions in cognitive functioning prior to dementia onset.

Social and general cognition are uniquely associated with social connectedness in later life.

The mechanisms by which older adults maintain large, complex social networks are not well understood. Prior work has primarily focused on general cognitive ability (e.g., executive function, episodic memory), largely overlooking social cognition-the ability to process, store, and remember social information. Because social cognition plays a key role in navigating social interactions and is distinct from general cognition, we examined whether general and social cognition uniquely predicted the nature of older adults' personal social networks. Our study leveraged comprehensive measures of general cognition (executive function, episodic memory), social cognition (face memory and dynamic measures of cognitive and affective theory of mind), and a rigorous measure of personal social networks from 143 community-dwelling older adults. We found that, when modeled together and controlling for sociodemographic variables, only executive function and dynamic cognitive theory of mind positively predicted having social networks with relatively unfamiliar, loosely connected others, accounting for 17% of the unique variance in older adults' social connectedness. Interestingly, having a social network comprised primarily of close, tightly knit relationships was negatively associated with affective theory of mind performance. Findings are discussed in the context of the social-cognitive resource framework-which suggests that social cognition may be more engaged in relatively unfamiliar, versus close, interactions. Specifically, our results show that social-cognitive processes may be relatively automatic for individuals whose primary social relationships are very close but may be more strongly engaged for individuals whose interactions include at least some relatively less close relationships. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Dynamic functional network connectivity and its association with lipid metabolism in Alzheimer's disease.

The study aims to examine the changing trajectory characteristics of dynamic functional network connectivity (dFNC) and its correlation with lipid metabolism-related factors across the Alzheimer's disease (AD) spectrum populations. Data from 242 AD spectrum subjects, including biological, neuroimaging, and general cognition, were obtained from the Alzheimer's Disease Neuroimaging Initiative for this cross-sectional study. The study utilized a sliding-window approach to assess whole-brain dFNC, investigating group differences and associations with biological and cognitive factors. Abnormal dFNC was used in the classification of AD spectrum populations by support vector machine. Mediation analysis was performed to explore the relationships between lipid-related indicators, dFNC, cerebrospinal fluid (CSF) biomarkers, and cognitive performance. Significant group difference concerning were observed in relation to APOE-ε4 status, CSF biomarkers, and cognitive scores. Two reoccurring connectivity states were identified: state-1 characterized by frequent but weak connections, and state-II characterized by less frequent but strong connections. Pre-AD subjects exhibited a preference for spending more time in state-I, whereas AD patients tended remain in state-II for longer periods. Group difference in dFNC was primarily found between AD and non-AD participants within each state. The dFNC of state-I yielded strong power to distinguish AD from other groups compared with state-II. APOE-ε4+, high polygenic score, and high serum lipid group were strongly associated with network disruption between association cortex system and sensory cortex system that characterized elevation of cognitive function, which may suggest a compensatory mechanism of dFNC in state-I, whereas differential connections of state-II mediated the relationships between APOE-ε4 genotype and CSF biomarkers, and cognitive indicators. The dysfunction of dFNC temporal-spatial patterns and increased cognition in individuals with APOE-ε4, high polygenic score, and higher serum lipid levels shed light on the lipid-related mechanisms of dynamic network reorganization in AD.

Postsurgical motor function and processing speed as predictors of quality of life in patients with chronic-phase glioblastoma

PurposePatients with glioblastomas (GBMs) have poor prognosis despite various treatments; therefore, attention should be paid to maintaining the quality of survival. Neurocognitive deficits can affect the quality of life (QOL) in patients with GBM. Most studies concerning QOL and neurocognitive functions have demonstrated a relationship between QOL and self-reported neurocognitive decline, although this method does not accurately reflect damaged functional domains. Therefore, this study aimed to clarify the neurocognitive functions that influence the QOL in patients with GBMs using an objective assessment of neurocognitive functions.MethodsData from 40 patients newly diagnosed with GBMs were analyzed. All patients completed the assessment of QOL and various neurological and neurocognitive functions including general cognitive function, processing speed, attention, memory, emotion recognition, social cognition, visuospatial cognition, verbal fluency, language, motor function, sensation, and visual field at 6 months postoperatively. QOL was assessed using the 36-Item Short Form Survey (SF-36). In the SF-36, the physical, mental, and role and social component summary (PCS, MCS, and RCS, respectively) scores were calculated. Multiple logistic regression analyses and chi-square tests were used to evaluate the association between SF-36 scores and neurocognitive functions.ResultsThe MCS was maintained, while the PCS and RCS scores were significantly lower in patients with GBMs than in healthy controls (p = 0.0040 and p < 0.0001, respectively). Among several neurocognitive functions, motor function and processing speed were significantly correlated with PCS and RCS scores, respectively (p = 0.0048 and p = 0.030, respectively). Patients who maintained their RCS or PCS scores had a higher probability of preserving motor function or processing speed than those with low RCS or PCS scores (p = 0.0026).ConclusionsMotor function and processing speed may be predictors of QOL in patients with GBMs.

Psychiatric Symptoms, Cognition, and Symptom Severity in Children

Mental illnesses are a leading cause of disability globally, and functional disability is often in part caused by cognitive impairments across psychiatric disorders. However, studies have consistently reported seemingly opposite findings regarding the association between cognition and psychiatric symptoms. To determine if the association between general cognition and mental health symptoms diverges at different symptom severities in children. A total of 5175 children with complete data at 2 time points assessed 2 years apart (aged 9 to 11 years at the first assessment) from the ongoing Adolescent Brain and Cognitive Development (ABCD) study were evaluated for a general cognition factor and mental health symptoms from September 2016 to August 2020 at 21 sites across the US. Polynomial and generalized additive models afforded derivation of continuous associations between cognition and psychiatric symptoms across different ranges of symptom severity. Data were analyzed from December 2022 to April 2024. Aggregate cognitive test scores (general cognition) were primarily evaluated in relation to total and subscale-specific symptoms reported from the Child Behavioral Checklist. The sample included 5175 children (2713 male [52.4%] and 2462 female [47.6%]; mean [SD] age, 10.9 [1.18] years). Previously reported mixed findings regarding the association between general cognition and symptoms may consist of several underlying, opposed associations that depend on the class and severity of symptoms. Linear models recovered differing associations between general cognition and mental health symptoms, depending on the range of symptom severities queried. Nonlinear models confirm that internalizing symptoms were significantly positively associated with cognition at low symptom burdens higher cognition = more symptoms) and significantly negatively associated with cognition at high symptom burdens. The association between mental health symptoms and general cognition in this study was nonlinear. Internalizing symptoms were both positively and negatively associated with general cognition at a significant level, depending on the range of symptom severities queried in the analysis sample. These results appear to reconcile mixed findings in prior studies, which implicitly assume that symptom severity tracks linearly with cognitive ability across the entire spectrum of mental health. As the association between cognition and symptoms may be opposite in low vs high symptom severity samples, these results reveal the necessity of clinical enrichment in studies of cognitive impairment.

Dietary patterns, inflammatory biomarkers and cognition in older adults: An analysis of three population-based cohorts

BackgroundTargeting effective strategies to prevent cognitive decline is key in the aging population. Some diets have been linked to a slower cognitive decline, potentially through reducing inflammation. We aimed at determining the effect of inflammatory dietary patterns (IDPs) on cognitive function in three population-based cohorts. MethodsIn this longitudinal study, we analyzed data from the Canadian Longitudinal Study of Aging, CoLaus|PsyCoLaus and Rotterdam Study. Our analytical sample included participants over 55 years old with baseline data on cognition, dietary intake, and inflammatory markers. IDPs were derived for each cohort using reduced rank regression to reflect maximal variation in three inflammatory markers. We calculated scores of consumption of the IDPs, higher scores indicating more IDP consumption. We used inverse probability of treatment and censoring weights in the marginal structural models to estimate associations of higher versus lower quarters of consumption of an IDP on general cognition (Mini-Mental State Evaluation) and four cognitive domains (memory, verbal fluency, verbal learning and processing speed and executive function) during at least 3 years of follow-up. ResultsWe included 10,366 participants (mean age 68) followed-up for a mean of 5 years. Diet explained between 1 and 2% of the variation of the inflammatory markers. There were no mean differences in general cognition when comparing the highest to the lowest quarter of consumption of IDPs among the three cohorts. Mean differences for the four cognitive domains were of small magnitude across cohorts and not clinically relevant. ConclusionDiet explained low variation in inflammatory markers. Consuming IDPs was not associated with mean differences in general or domain-specific cognitive function.

Longitudinal Associations Between Cognition and Grip Strength, Differentiated by Sex and Physical Activity: A Population-Based Study in Older Adults From 17 European Countries.

Objectives (1) To investigate longitudinal associations between grip strength (GS) and cognition over 4 years in European older adults, (2) to examine differences in temporal associations between men and women and between levels of physical activity, (3) to explore in each year 2015 and 2019 associations between GS quartiles and cognitive performance, and (4) to explore longitudinal associations between GS quartiles (year 2015) and cognitive performance (year 2019). Methods: 25,281 individuals (14,200 women) from 17 European countries aged ≥50 years responded to waves 6th and 8th of the SHARE project. We analyzed GS, a general cognition index, and physical activity level. Results: Panel analyses revealed a bidirectional relationship over 4 years between GS and cognition, with differences between sex, as well as between participants with moderate-to-vigorous and low physical activity levels. Conclusion: Women and participants with low physical activity were more likely to experience cognitive performance deficits 4 years later.

The Influence of Vision Impairment on the Measurement of Cognition in Older Adults in India: Findings From LASI-DAD.

Prior investigations have not considered whether poor vision biases cognitive testing. However, such research is vital given increasing evidence that vision impairment (VI) may be an important modifiable risk factor for dementia, particularly in low- and middle-income settings where the prevalence of VI is high. This study employed data from 3784 participants in Wave 1 of the Longitudinal Aging Study in India-Diagnostic Assessment of Dementia (LASI-DAD) who underwent both visual acuity and cognitive function testing. We used multiple indicators and multiple causes models to assess differential item functioning (DIF; eg, bias) in cognitive testing by objectively measured distance and near VI. Multivariable linear regression was used to model the association between VI and cognitive factor scores before and after DIF adjustment. Analyses were performed for general cognition and separate cognitive domains, corresponding to memory, language/fluency, executive functioning, and visuospatial performance. Models were adjusted for demographic, health, and socioeconomic covariates. Participants in our sample were 60 and older. Most participants with VI were 60-69 years old (59.6%) and 50.8% were female. Individuals experiencing both distance and near VI tended to be older, have lower educational attainment, be married, reside in rural settings, and belong to lower consumption and BMI categories. Both distance and near VI were associated with poorer cognition before and after DIF-adjustment. Differences between DIF-unadjusted and -adjusted scores were small compared to the standard error of measurement, indicating no evidence of meaningful measurement differences by VI. In well-conducted large-scale surveys, bias in cognitive testing due to VI is likely minimal. Findings strengthen previous evidence on the association between VI and dementia by showing that such associations are unlikely to be attributable to vision-related measurement error in the assessment of cognitive functioning.

Grid Cells in Cognition: Mechanisms and Function.

The activity patterns of grid cells form distinctively regular triangular lattices over the explored spatial environment and are largely invariant to visual stimuli, animal movement, and environment geometry. These neurons present numerous fascinating challenges to the curious (neuro)scientist: What are the circuit mechanisms responsible for creating spatially periodic activity patterns from the monotonic input-output responses of single neurons? How and why does the brain encode a local, nonperiodic variable-the allocentric position of the animal-with a periodic, nonlocal code? And, are grid cells truly specialized for spatial computations? Otherwise, what is their role in general cognition more broadly? We review efforts in uncovering the mechanisms and functional properties of grid cells, highlighting recent progress in the experimental validation of mechanistic grid cell models, and discuss the coding properties and functional advantages of the grid code as suggested by continuous attractor network models of grid cells.

Understanding the Psychosis Spectrum Using a Hierarchical Model of Social Cognition.

Social cognitive impairments are central to psychosis, including lower severity psychosis-like experiences (PLEs). Nonetheless, progress has been hindered by social cognition's poorly defined factor structure, as well as limited work examining the specificity of social cognitive impairment to psychosis. The present study examined how PLEs relate to social cognition in the context of other psychopathology dimensions, using a hierarchical factors approach to social cognition. Online community participants (N = 1026) completed psychosis, autism, and personality disorder questionnaires, as well as 3 social cognitive tasks that varied in methodology (vignette vs video) and construct (higher- vs lower-level social cognition). Exploratory (EFA) and confirmatory factor analyses (CFA) were used to model social cognition, with the best models being examined in association with PLEs and psychopathology dimensions. EFA and CFA supported a hierarchical model of social cognition, with 2 higher-order factors emerging: verbal/vignette task methodology and a multimethod general social cognition factor. These higher-order factors accounted for task-level associations to psychopathology, with relations to positive symptoms (r = .23) and antagonism (r = .28). After controlling for other psychopathology, positive symptoms were most clearly related to tasks with verbal methodology (β = -0.34). These results suggest that broad social cognitive processes and method effects may account for many previous findings in psychosis and psychopathology research. Additionally, accounting for broad social cognitive impairment may yield insights into more specific social cognitive processes as well.

Brain activations elicited during task-switching generalize beyond the task: A partial least squares correlation approach to combine fMRI signals and cognition.

An underlying hypothesis for broad transfer from cognitive training is that the regional brain signals engaged during the training task are related to the transfer tasks. However, it is unclear whether the brain activations elicited from a specific cognitive task can generalize to performance of other tasks, esp. in normal aging where cognitive training holds much promise. In this large dual-site functional magnetic resonance imaging (fMRI) study, we aimed to characterize the neurobehavioral correlates of task-switching in normal aging and examine whether the task-switching-related fMRI-blood-oxygen-level-dependent (BOLD) signals, engaged during varieties of cognitive control, generalize to other tasks of executive control and general cognition. We therefore used a hybrid blocked and event-related fMRI task-switching paradigm to investigate brain regions associated with multiple types of cognitive control on 129 non-demented older adults (65-85 years). This large dataset provided a unique opportunity for a data-driven partial least squares-correlation approach to investigate the generalizability of multiple fMRI-BOLD signals associated with task-switching costs to other tasks of executive control, general cognition, and demographic characteristics. While some fMRI signals generalized beyond the scanned task, others did not. Results indicate right middle frontal brain activation as detrimental to task-switching performance, whereas inferior frontal and caudate activations were related to faster processing speed during the fMRI task-switching, but activations of these regions did not predict performance on other tasks of executive control or general cognition. However, BOLD signals from the right lateral occipital cortex engaged during the fMRI task positively predicted performance on a working memory updating task, and BOLD signals from the left post-central gyrus that were disengaged during the fMRI task were related to slower processing speed in the task as well as to lower general cognition. Together, these results suggest generalizability of these BOLD signals beyond the scanned task. The findings also provided evidence for the general slowing hypothesis of aging as most variance in the data were explained by low processing speed and global low BOLD signal in older age. As processing speed shared variance with task-switching and other executive control tasks, it might be a possible basis of generalizability between these tasks. Additional results support the dedifferentiation hypothesis of brain aging, as right middle frontal activations predicted poorer task-switching performance. Overall, we observed that the BOLD signals related to the fMRI task not only generalize to the performance of other executive control tasks, but unique brain predictors of out-of-scanner performance can be identified.

Developmental, Cognitive, Ocular Motor, and Neuroimaging Findings Related to SUFU Haploinsufficiency: Unraveling Subtle and Highly Variable Phenotypes

BackgroundBiallelic SUFU variants have originally been linked to Joubert syndrome, comprising cerebellar abnormalities, dysmorphism, and polydactyly. In contrast, heterozygous truncating variants have recently been associated with developmental delay and ocular motor apraxia, but only a limited number of patients have been reported. Here, we aim to delineate further the mild end of the phenotypic spectrum related to SUFU haploinsufficiency. MethodsNine individuals (from three unrelated families) harboring truncating SUFU variants were investigated, including two previously reported individuals (from one family). We provide results from a comprehensive assessment comprising neuroimaging, neuropsychology, video-oculography, and genetic testing. ResultsWe identified three inherited or de novo truncating variants in SUFU (NM_016169.4): c.895C>T p.(Arg299∗), c.71dup p.(Ala25Glyfs∗23), and c.71del p.(Pro24Argfs∗72). The phenotypic expression showed high variability both between and within families. Clinical features include motor developmental delay (seven of nine), axial hypotonia (five of nine), ocular motor apraxia (three of nine), and cerebellar signs (three of nine). Four of the six reported children had macrocephaly. Neuropsychological and developmental assessments revealed mildly delayed language development in the youngest children, whereas general cognition was normal in all variant carriers. Subtle but characteristic SUFU-related neuroimaging abnormalities (including superior cerebellar dysplasia, abnormalities of the superior cerebellar peduncles, rostrally displaced fastigium, and vermis hypoplasia) were observed in seven of nine individuals. ConclusionsOur data shed further light on the mild but recognizable features of SUFU haploinsufficiency and underline its marked phenotypic variability, even within families. Notably, neurodevelopmental and behavioral abnormalities are mild compared with Joubert syndrome and seem to be well compensated over time.

Opium tincture has anti-propulsive effects in patients with chronic diarrhea: a randomized, placebo-controlled, and cross-over trial

Objective Chronic diarrhea affects approximately 5% of the population. Opioids inhibit gastrointestinal motility, and opium tincture has shown anti-propulsive effects in healthy, but no controlled studies of its clinical efficacy exist. We aimed to investigate the anti-propulsive and central nervous system (CNS) effects of opium tincture in patients with chronic diarrhea. Materials and methods The study was a randomized, double-blinded, placebo-controlled, cross-over trial in subjects with chronic diarrhea refractory to standard treatment. Participants received opium tincture or placebo during two intervention periods, each lasting seven days. Bowel movements were recorded daily, and gastrointestinal transit time was investigated with the wireless motility capsule system. Gastrointestinal symptoms, health-related quality of life, and CNS effects (pupil size, reaction time, memory, and general cognition) were also investigated, along with signs of addiction. Results Eleven subjects (mean age: 45 ± 17 years, 46% males) with a median of 4.7 daily bowel movements were included. The number of daily bowel movements was reduced during opium tincture treatment to 2.3 (p = 0.045), but not placebo (3.0, p = 0.09). Opium tincture prolonged the colonic transit time compared to placebo (17 h vs. 12 h, p < 0.001). In both treatment arms, there were no changes in self-reported gastrointestinal symptoms, health-related quality of life, or CNS effects, and no indication of addiction was present. Conclusion Opium tincture induced anti-propulsive effects in patients with chronic diarrhea refractory to standard treatment. This indicates that opium tincture is a relevant treatment strategy for selected patients with chronic diarrhea. Moreover, no evidence of opioid-induced sedation or addiction was found. Trial Registration Number: NCT05690321 (registered 2023-01-10)

Effect of Summer Holiday Programs on Children's Mental Health and Well-Being: Systematic Review and Meta-Analysis.

Poor youth mental health is an area of global concern. Summer holiday programs may provide environments that support mental health when the structures and supports of school are not available. The aim of this review was to determine the effectiveness of summer holiday programs in improving the mental health, social-emotional well-being, and cognitive (non-academic) outcomes of children and adolescents. Studies of summer holiday programs for school-aged children (5-18 years) were included if they measured any mental, socio-emotional or cognitive (non-academic) outcome. Studies were excluded if they were published prior to 2000, targeted clinical populations or lasted less than five days. Six databases were searched (April 2023). Risk of bias was assessed using the PEDro tool. Study outcomes were grouped according to three main constructs: mental health (psychological well-being, anxiety, depression, distress, and self-perception including self-esteem, self-worth, self-concept, confidence, and competence); social-emotional well-being (behavior and social skills, e.g., communication, bullying, conflict resolution, empathy, and social skills); and cognitive function (memory, selective attention, and executive function). A fourth "other" group captured substance use, personality traits, character skills, and values. Effect sizes were calculated as the standardized mean difference between pre- and post-intervention scores. The synthesis involved a random-effects meta-analysis (presented in forest plots), where possible, with the remaining outcomes narratively synthesized. Twenty-six studies (n = 6812 participants) were included. The results of the meta-analysis suggested that summer programs showed a statistically non-significant trend toward reducing symptoms of anxiety and depression (k = 2 studies, SMD = -0.17, 95% CI -2.94, 2.60), psychological distress (k = 2 studies, SMD -0.46, 95% CI -1.71, 0.79), and no effect on self-esteem (k = 6 studies, SMD = 0.02, 95% CI -0.02, 0.06) or self-worth (k = 3 studies, SMD = 0.05, 95% CI 0.00, 0.11). Narrative syntheses indicated a pattern toward improvements in general mental health, self-perception, social-emotional outcomes, and cognition. Studies were generally small, with a high risk of bias. Summer holiday programs for children and adolescents show trends toward improving mental, social, emotional, and cognitive outcomes. Programs targeting disadvantaged children showed stronger patterns of improvement related to mental health and self-perception than programs targeting the general population. While effect sizes are small to negligible, they consistently indicate improvements. Summer programs present a promising avenue to promote mental health in children; however, further rigorously designed, clearly reported control-group studies are required to more fully understand their effects.

Dysglycemia, gender, and cognitive performance in older persons living with mild cognitive impairment: findings from a cross-sectional, population-based study

ObjectiveThis study aims to examine the relationship between dysglycemia - also known as pre-diabetes or impaired glucose tolerance- and cognitive abilities in an older population living Mild Cognitive Impairment (MCI) and stratified by gender.Study designThis is a retrospective study with data gathered from a large Italian clinical-based database.Main outcome measuresThe evaluation of cognitive performances by the Mini-Mental State Examination and the Addenbrooke’s Cognitive Examination Revised rating scale as tests of screening and a comprehensive neuropsychological evaluation of several cognitive areas.ResultsThe study comprised 682 subjects (445 F/237 M) with a mean age of 76.08 ± 9.03 (range: 66–93) years. In all population, subjects with dysglycemia 193 (28.3%) had significantly poorer performance in memory (p = 0.006) and logic reasoning (p = 0.007) when compared with subjects without dysglycemia. The linear regression analyses revealed significant differences in the correlates of cognitive domains between gender groups. Independent of multiple covariates, women with dysglycemia showed worse performances in attention and short-term memory domains as compared with men. Even in the absence of dysglycemia women were more likely to show lower score in screening test of general cognition and attention.ConclusionsOur findings suggest that dysglycemia in older individuals with MCI is associated with declines in specific cognitive domains, potentially influenced by gender. Implementing a comprehensive approach involving risk stratification and preventive strategies may be more effective in averting further cognitive decline in this high-risk population.