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PubMed2026

Cerebral Cortical Structural Variation and General Cognitive Ability: Evidence From Mendelian Randomization.

Understanding the cortical architecture underlying individual differences in general cognitive ability (GCA) remains a central question in cognitive neuroscience. Prior work has established associations between global brain size and GCA, yet the regional effects and directionality of these relationships remain debated. Using a genetically informed cortical parcellation in 11,289 UK Biobank participants, we examined associations between cortical surface area (SA), cortical thickness (CT), and GCA measured via verbal-numerical reasoning. Total SA showed a robust positive association with GCA. At the regional level, dorsolateral prefrontal and superior temporal SA exhibited the strongest positive associations, which persisted after adjustment for global SA. In contrast, CT showed comparatively modest associations. Using Mendelian randomization (MR) with genome-wide significant genetic instruments, we observed evidence consistent with a bidirectional relationship between total SA and GCA. At the regional level, dorsolateral prefrontal and temporal SA demonstrated evidence of MR-inferred directional effects on GCA, while GCA showed evidence of MR-inferred directional effects on total SA and perisylvian thickness. These findings support a polyregional SA architecture underlying GCA, with prominent contributions from prefrontal and temporal association cortices. Our results refine global brain-GCA models and highlight the value of genetically informed parcellation for identifying regional cortical contributions.

Humans↗

PubMed2026

Shared genetic architecture between ADHD and intelligence varies across ADHD subtypes.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental condition frequently accompanied by cognitive difficulties. Although previous genetic studies have demonstrated substantial overlap between ADHD and intelligence, most have treated ADHD as a single phenotype. However, whether this shared genetic architecture differs across ADHD subtypes remains unclear. METHODS: We conducted a genome-wide cross-trait analysis integrating large-scale genome-wide association study (GWAS) datasets of overall ADHD, its subtypes-childhood ADHD, persistent ADHD, and late-diagnosed ADHD-and intelligence (total N > 300,000). Genome-wide genetic correlations, polygenic overlap, local genetic correlations, and variant-level associations between ADHD phenotypes and intelligence were evaluated to characterize their shared genetic architecture. Shared variants were identified through cross-trait enrichment analyses and subsequently mapped to genes for functional annotation and gene-set enrichment. Bidirectional associations were evaluated using two-sample Mendelian randomization with sensitivity analyses. Additional GWAS datasets were used to validate the robustness of shared loci by assessing the consistency of effect directions. RESULTS: All ADHD phenotypes showed significant negative genetic correlations with intelligence (rg ranging from -0.3442 to -0.4205). Despite these modest genome-wide correlations, cross-trait analyses revealed substantial genetic overlap, including polygenic overlap, local genetic correlations, and variant-level associations. We identified 184 loci jointly associated with ADHD traits and intelligence, including 64 novel loci, whereas no shared loci were detected for persistent ADHD under the current analysis. Functional annotation revealed biologically distinct enrichment patterns across subtypes: childhood ADHD loci were linked to early neurodevelopmental processes, while late-diagnosed ADHD loci were enriched in synapse-related and neuronal signaling pathways. Mendelian randomization analyses suggested bidirectional associations, with stronger evidence supporting a directional association from intelligence to ADHD risk. Furthermore, these shared loci showed largely consistent effect directions across additional GWAS datasets, providing support for the robustness of the findings. CONCLUSIONS: The shared genetic architecture between ADHD and intelligence varies across ADHD subtypes, highlighting distinct biological pathways underlying cognitive heterogeneity in ADHD. These findings suggest that the relationship between ADHD liability and general cognitive ability is not uniform across ADHD subtypes and may inform future research on risk stratification and early identification in child and adolescent psychiatry.

Humans↗

PubMed2025

Distinguishing specific from broad genetic associations between external correlates and common factors.

MOTIVATION: Within the genomic structural equation modelling (genomic SEM) framework, common factors are often used to index shared genetic etiology across constellations of genome-wide associations studies (GWASs) phenotypes. A standard common pathway model, in which a genetic association is estimated between an external GWAS phenotype and a common factor, assumes that all genetic associations between the external GWAS phenotype and the individual indicator phenotypes are mediated through the factor. This assumption can be tested using the QTrait statistic, which compares the common pathway model to an independent pathways model that allows for direct genetic associations between the external GWAS phenotype and the individual indicators of the factor. However, QTrait is not designed to identify either the magnitude or the source of this heterogeneity. RESULTS: We expand upon the QTrait approach by describing an effect size index that quantifies the degree to which the common pathways model is violated, and we provide a systematic approach for empirically identifying specific direct pathways between an external trait and indicator traits. Our method comprises a series of omnibus tests and outlying indicator detection algorithms indexing the heterogeneity of associations between the genetic component of external traits and the individual indicators of common factors. We provide a set of automated functions which we apply to investigate the patterns of genetic associations across a set of external correlates with respect to indicators of general cognitive ability and case-control and proxy GWAS indices of Alzheimer's disease. AVAILABILITY AND IMPLEMENTATION: The Genomic SEM R package and the QTrait function is available at https://github.com/GenomicSEM/GenomicSEM. The QTrait function tutorial is available at https://github.com/GenomicSEM/GenomicSEM/wiki/8.-Tutorials. To ensure reproducibility of the analyses presented in this manuscript, the exact version of the QTrait function used, along with input data and scripts, has been archived on Zenodo (DOI: https://doi.org/10.5281/zenodo.17186083).

Genome-Wide Association Study↗

PubMed2026

The asymmetry of working memory training transfer: A systematic review and meta-analysis.

Working memory (WM) training is widely used to enhance cognitive performance; however, its transfer to untrained tasks remains controversial. Traditional theories emphasize task similarity as the primary determinant of training transfer, but they cannot fully explain emerging evidence of asymmetric transfer across tasks. Two directional transfer hypotheses are proposed here to explain this asymmetry: the resource-based transfer advantage hypothesis predicts stronger transfer from more to less cognitively demanding tasks, whereas the ability-based transfer advantage hypothesis predicts stronger transfer from tasks engaging broader task-general abilities to tasks engaging task-specific narrower abilities. The contrast between span and updating paradigms provides an informative framework for distinguishing these accounts, because updating tasks are generally more cognitively demanding, whereas span tasks involve broader abilities. Accordingly, we conducted a three-level meta-analysis of 55 studies (208 effect sizes; N = 3,492). The results showed that updating training transferred reliably to span tasks (g = 0.176, p < .001), whereas span training did not reliably transfer to updating tasks (g = 0.048, p = .453), supporting the resource-based account. This advantage of updating training also extended to non-WM outcomes and was more pronounced at lower training doses, in non-adult samples, and with verbal stimuli. Together, these findings extend WM transfer theory beyond task similarity by highlighting the importance of cognitive demand and offer guidance for WM training design.

Humans↗

PubMed1979

[Experiences with research on pharmacopsychological effects on older people].

During the last years we tested a number of cerebral vasoactive and cerebral metabolic active substances on aged people with the help of the double blind method against with placebo in order to measure the change of the "nutritive insufficiency" with its neurophysiological and vascular-psychological syndromes under pharmacological influence. We used psychological test instruments (groups of 60-80 patients between 50 and 70 years). Duration of the treatment was 3-4 months. Analysis of the dates by way of variance and covariance analysis. Significant results of successive treatments were achieved: improvements of the mental ability as far as the functions of the memory are concerned, higher capacity of attention and concentration (vigilance), fluency and adaptability of cognitive functions, increasing openess of mind and the ability of experiencing, improvement of the general mood and good health. Longer lasting effects in comparison of the drugs were noticed only after treatment with metabolic agents. Publication is planned.

Aged↗

PubMed1978

Education in rheumatology for the primary care physician.

An international workshop considered rheumatological education of the primary care physician. All medical students need exposure to rheumatology. Emphasis should be on the musculoskeletal component and on the better defined diseases. During the postdoctoral years, principles of total health care need to be taught by well trained rheumatologists in tertiary care rheumatic disease units with comprehensive ambulatory care facilities. Continuing education of the generalist needs to be relevant to his professional competence. He needs to acquire and update the knowledge to manage common rheumatic diseases and to learn when to ask for help. General educational objectives are applicable to the field of rheumatology: cognitive skills bring knowledge of the scientific basis and clinical facts; motor skills--the ability to examine competently patients with rheumatic diseases; affective skills--the understanding of and capacity to deal with chronic illness.

Curriculum↗

PubMed1979

Factors affecting walking in a profoundly retarded population.

A total of 127 children with profound mental retardation were reviewed to determine the age at which walking began. 53 per cent of the children walked at a median age of 30 months. Further sub-classification revealed that both the number of ambulatory children and their age at walking varied with degree of neurological handicap, children with additional neurological problems having a higher median age for beginning to walk. The minimal cognitive level required for walking remains unknown, but is probably less than generally accepted. In this profoundly retarded population, the existence of neurological factors was associated with both increased age at walking and with decreased ability to walk.

Brain Damage, Chronic↗

PubMed1977

The influence of pyrithioxine on certain factors of intelligence1.

A double-blind trial with pyrithioxine was made with 22 pairs of visually handicapped children who were equal in IQ scores and in chronological age. Although an improvement of abstraction ability was noticed, the overall results were not in concurrence with the general tendency in relevant literature.

Achievement↗

PubMedDate not supplied

Cross-sectional analysis of cognitive functioning across the life-span.

Performance on Piagetian logical concept tasks, standardized intellectual measures, and measures of memory ability, was assessed cross-sectionally. One-hundred-sixty individuals participated. Differential item difficulty patterns were noted on the Piagetian tasks. Curvilinear trends were evident for class inclusion, combinatorial reasoning, and conservation of surface area. Factorial analyses of variance revealed significant chronological age main effects for all tasks except transitivity of weight. Covariance analyses indicated that educational level is generally more closely related to logical concept performance than is chronological age. Dimensional analyses revealed separate factors for general intelligence, classification, relations, and conservation. The youngest and oldest age groups has similar factor patterns; these differed from those of the mature participants.

Adolescent↗

PubMed1979

EEG patterns during 'cognitive' tasks. II. Analysis of controlled tasks.

This experiment was designed to distinguish possible EEG correlates of the cognitive components of tasks from EEG patterns associated with stimulus characteristics, limb and eye movements, and performance-related factors such as subjects' ability and effort. Thirty-two right-handed adults each performed 30 trials, lasting 6-15 sec each, of four simplified, controlled tasks: mental rotation of geometric forms, serial addition of a column of signed digits, substitution of letters with subsequent word recognition and visual fixation. The first three tasks could not be differentiated from each other. Each of these tasks could be differentiated from visual fixation by approximately 10% generalized reductions in alpha and beta band intensities, and slight increases in theta band intensities frontally and occipitally. We conclude that the EEG patterns which differentiated the complex tasks described in Part I were due to inter-task differences in stimulus characteristics, efferent activities and/or performance-related factors, rather than to cognitive differences. With these controls, no evidence for lateralization of different types of cognitive activity was found in the EEG.

Adult↗

PubMed1977

The relationship between impaired selective attention and severity of psychopathology in acute psychiatric patients.

Thirty acute psychiatric patients were administered a battery of selective attention and cognitive ability measures to determine whether there is a differential deficit in filtering capacity with increasing degrees of psychopathology. Susceptibility to intrusions in the early stages of auditory selective attention was positively related to degree of disturbance, but no more so than were other cognitive disabilities. Slowness of information processing, rather than impaired selective attention, bore the strongest relationship to severity of disturbance and appeared to be the best index of general cognitive inefficiency. It was concluded that the defective filter theories of schizophrenic deficit hold little promise for explaining how psychopathology affects cognitive functioning across a continuum of levels of disturbance.

Acute Disease↗

PubMed1978

Comparison of the neuropsychological deficits associated with early and advanced Huntington's disease.

Patients with "recently" diagnosed Huntington's Disease (RHD) were compared on a neuropsychological test battery to patients who have had the disease three to 15 years (AHD) and to intact controls. While the patients with HD showed general nonfocal deficits on the Wechsler Adult Intelligence Scale, the Wechsler Memory Scale, and tests of short-term memory and verbal fluency, the patients with RHD had focal deficits that stressed their memory deficits. The patients with RHD had IQs within the normal range, but their memory quotients, their performance on short-term memory tests, and their ability to search and retrieve from long-term memory were severely imparied. These results suggest that the cognitive deficits of patients with HD do not develop uniformally; memory disorders are early focal signs that precede the patients' more widespread intellectual deterioration.

Adult↗

PubMed2025

Genomic and Developmental Models to Predict Cognitive and Adaptive Outcomes in Autistic Children.

IMPORTANCE: Although early signs of autism are often observed between 18 and 36 months of age, there is considerable uncertainty regarding future development. Clinicians lack predictive tools to identify those who will later be diagnosed with co-occurring intellectual disability (ID). OBJECTIVE: To predict ID in children diagnosed with autism. DESIGN, SETTING, AND PARTICIPANTS: This prognostic study involved the development and validation of models integrating genetic variants and developmental milestones to predict ID. Models were trained, cross-validated, and tested for generalizability across 3 autism cohorts: Simons Foundation Powering Autism Research (SPARK), Simons Simplex Collection, and MSSNG. Autistic participants were assessed older than 6 years of age for ID. Study data were analyzed from January 2023 to July 2024. EXPOSURES: Ages at attaining early developmental milestones, occurrence of language regression, polygenic scores for cognitive ability and autism, rare copy number variants, de novo loss-of-function and missense variants impacting constrained genes. MAIN OUTCOMES AND MEASURES: The out-of-sample performance of predictive models was assessed using the area under the receiver operating characteristic curve (AUROC), positive predictive values (PPVs), and negative predictive values (NPVs). RESULTS: A total of 5633 autistic participants (4574 male [81.2%]) were included in this analysis. On average, participants were diagnosed with autism at 4 (IQR, 3-7) years of age and assessed for ID at 11 (8-14) years of age, with 1159 participants (20.6%) being diagnosed with ID. The model integrating all predictors yielded an AUROC of 0.653 (95% CI, 0.625-0.681), and this predictive performance was cross-validated and generalized across cohorts. This modest performance reflected that only a subset of individuals carried large-effect variants, high polygenic scores, or presented delayed milestones. However, combinations of genetic variants that are typically not considered clinically relevant by diagnostic laboratories achieved PPVs of 55% and correctly identified 10% of individuals developing ID. The addition of polygenic scores to developmental milestones specifically improved NPVs rather than PPVs. Notably, the ability to stratify ID probabilities using genetic variants was up to 2-fold higher in individuals with delayed milestones compared with those with typical development. CONCLUSIONS AND RELEVANCE: Results of this prognostic study suggest that the growing number of neurodevelopmental condition-associated variants cannot, in most cases, be used alone for predicting ID. However, models combining different classes of variants with developmental milestones provide clinically relevant individual-level predictions that could be useful for targeting early interventions.

Humans↗

PubMed2025

Heterogeneity Analysis of Associations Involving the Large-Scale Online MindCrowd Survey Memory Test.

INTRODUCTION: Alzheimer's disease and related disorders (ADRDs), as well as general age-related cognitive decline, are known to be multifactorial with heterogeneous etiologies. Identifying and accommodating heterogeneity in any one ADRD-related data set can be pursued using different analytical techniques, each with different assumptions or purposes. For example, whereas a great deal of research has explored clustering individuals or variables that exhibit greater similarity in some way, little research has explored evidence for heterogeneity in the relationships between relevant outcomes, such as performance on a memory test, and risk factors such as environmental exposures, behaviors, or genetic factors among individuals. METHODS: We explored evidence of heterogeneity in the relationships between ability on a memory test, specifically the paired associate learning (PAL) test, and multiple social and demographic risk factors using the large MindCrowd study database (n > 90,000 individuals). We focused on mixtures of regression models but compared models assuming many interaction effects among independent variables as well as random effects. RESULTS: We ultimately find substantial evidence for heterogeneity and offer an intuitive explanation for it involving individual motivation for participating in the MindCrowd study. Basically, we argue that our mixture of regression model analysis results suggest that a smaller group of individuals (∼16%) likely participated in the MindCrowd study out of a concern for their cognitive abilities as they exhibit stronger and statistically significant negative associations between age, number of medications they are on, some ancestries, and the number correct on the PAL test. They also exhibit stronger positive associations between education and PAL test results in a dose-dependent manner suggesting that a "cognitive reserve" associated with greater education could benefit them. Analysis models assuming interaction terms and random effects suggested that other forms of heterogeneity in the relationships between variables exist in the data set, but their results do not carry with them the same intuitive explanation that the results of the mixture model analyses do. CONCLUSION: We find evidence for heterogeneity in the relationships between social and demographic variables and PAL test results in the large MindCrowd study database. This heterogeneity is likely due to individuals with and without concerns for their cognitive abilities participating in the study. We also find other types of evidence in the data set. Our results should motivate caution in the use of large epidemiological study or survey-oriented data sets to build predictive models of clinical or subclinical pathologies without exploring or accommodating heterogeneity. Our results also suggest that one should include questions about motivation to participate in large epidemiological studies since different motivations may impact important relationships between independent and dependent variables.

Humans↗

PubMed2026

Effects of adjunctive memantine on executive function and global cognition in bipolar disorder (BD): A randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Cognitive impairment contributes substantially to disability in bipolar disorder (BD), but effective pharmacologic options remain limited. This trial evaluated whether adjunctive memantine improves global cognition and executive function in BD. METHODS: In this double-blind, placebo-controlled randomized trial, patients with bipolar I disorder (B1D) receiving lithium and olanzapine were assigned to memantine or placebo. Memantine was titrated to 20 mg/day over 6 weeks. Cognitive outcomes were assessed at baseline, week 6, and week 18. Global cognition was measured with the Neurocognitive Assessment Battery (NuCog), and executive function with the Frontal Assessment Battery (FAB). Data were analyzed using generalized estimating equations and Bonferroni-adjusted post-hoc tests. RESULTS: Sixty-three participants were randomized (memantine, n = 31; placebo, n = 32), and all completed follow-up. Groups were comparable at baseline for demographic and clinical variables and for most cognitive measures. Both groups improved over time (P < 0.001), but improvement was greater with memantine for global cognition at week 6 (MD = 9.32; 95% CI, 4.84-13.81; P < 0.001) and week 18 (MD = 12.69; 95% CI, 8.67-16.71; P < 0.001). FAB total scores favored memantine at week 18 (MD = 2.68; 95% CI, 1.76-3.61; P < 0.001), but not at week 6. Domain analyses showed significant benefits for NuCog attention, visuoconstructional ability, memory, and executive function, and for several FAB subscales by week 18. CONCLUSIONS: Adjunctive memantine improved global cognition and, over longer follow-up, executive function in BD. These findings support NMDA receptor modulation as a potential strategy for cognitive dysfunction in BD.

Humans↗

PubMed2025

Impact of Chewing Behavior Change on Cognition and Cerebral Hemodynamics.

BACKGROUND: Impaired chewing ability is a recognized risk factor for cognitive decline in older adults, potentially due to reduced neural stimulation in cognition-related brain regions. While short-term studies have demonstrated transient increases in neural activity from chewing, the sustained cognitive and neurophysiological effects of encouraging thorough chewing habits in daily life remain unclear. OBJECTIVE: This randomized controlled trial investigated whether promoting thorough chewing during meals could improve cognitive function and cerebral hemodynamics in older adults. METHODS: Fifty participants aged 65 y or older were randomly assigned to either a 1-mo intervention group, which used a wearable device to monitor and increase chewing strokes during meals, or a control group that maintained usual chewing habits. Chewing behavior, cognitive performance (including memory and executive function via the color Stroop test), and cerebral hemodynamics in the dorsolateral prefrontal cortex (DLPFC) were measured at baseline and after 1 mo. Statistical analyses included t tests, chi-square tests, 2-way analysis of variance with post hoc tests, Pearson correlations, and generalized linear models to evaluate group differences and associations between chewing and cognitive outcomes. RESULTS: Significant time-by-group interactions were observed for memory, F(1, 48) = 6.24, P = 0.043, and hemodynamic responses in the left DLPFC, F(1, 48) = 6.19, P = 0.013. The intervention group showed increased chewing frequency (P = 0.017), improved memory performance, and reduced left DLPFC responses compared with controls. Chewing frequency was positively correlated with Stroop test scores (r = 0.53, P = 0.010) and negatively with hemodynamic changes in the left DLPFC (r = -0.30, P = 0.040). Although improvements in other cognitive outcomes and hemodynamic measures favored the intervention group, these differences did not reach statistical significance. CONCLUSIONS: Promoting intentional chewing habits for 1 mo may enhance memory-related cognitive performance and neural efficiency in the DLPFC during working memory tasks in older adults. This nonpharmacologic, low-burden strategy warrants further research with longer interventions to support cognitive health and dementia prevention. TRIAL REGISTRATION ID: UMIN000044280Knowledge Transfer Statement:This study demonstrates that promoting thorough chewing habits in older adults can improve memory and enhance neural efficiency in the brain. Encouraging intentional mastication is a simple, nonpharmacologic approach that may help maintain cognitive health and prevent dementia, providing a practical strategy for clinicians and policymakers to support healthy aging.

Humans↗

PubMed1978

Locus of control research on alcoholic populations: a review. II. Relationship to other measures.

Research literature dealing with the relationships of locus of control to age, ability to function, and personality traits is reviewed. Results are contradictory on the relationship of locus of control in alcoholics to age, social desirability, and intellectual functioning. There is some tendency for internality to be related to better social functioning and the defenses of denial, intellectualization, and repression. There is some possible support for a relationship of externality and anxiety, and externality does appear related to helplessness, depression, isolation, general clinical pathology, and the defense of turning against another. No relationship has been found between locus of control and field dependence for alcoholics. Methodological difficulties have included problems with sampling, unsystematic research, assuming homogeneity of alcoholic samples, and assuming linearity and unidimensionality of the scales. Possible research which could clarify some of the areas are suggested.

Age Factors↗

PubMed1978

External validity in the assessment of intellectual development in adulthood.

The relation of intelligence and competence is discussed and external validity issues are examined for the dimensions of settings, measurement variables, treatment variables and experimental units. It is argued that external validity across situations and life stages cannot be obtained for any single measure of intellectual ability. External validity problems are exacerbated beyond young adulthood since single criterion goals comparable to that of educational aptitude in work with the young are not available, and tasks do not retain ecological validity when the situational context of the individual under study changes due to developmental progression and idiosyncratic modification of individual life situation and roles. External validity in adulthood must therefore be addressed by examining task-by-person-by-situation interfaces separately for different life stages and across cohort groupings. A major test construction and validation program is outlined, and examples are given showing how some of the aspects of such a program can be operationalized.

Cognition↗