BACKGROUND: In phase 3 trials, ozanimod reduced brain atrophy and improved cognitive processing speed compared with interferon β-1a (IFN) in participants with relapsing multiple sclerosis (RMS). OBJECTIVES: To assess long-term brain volume changes and associations with clinical/cognitive outcomes during an open-label extension ([OLE] DAYBREAK [NCT02576717]). METHODS: Completers of phase 3 "parent" trials were eligible to receive ozanimod 0.92 mg in DAYBREAK. Whole brain, thalamic, and cortical gray matter volumes (WBV, TV, and CGMV, respectively) were analyzed annually. RESULTS: Participants receiving continuous ozanimod had sustained, low rates of WBV loss through OLE month (M)60 (annualized least-squares mean percent change from parent baseline: RADIANCE, -0.27; SUNBEAM, -0.35). Compared with participants switched from IFN, these participants had lower reductions in WBV (parent baseline through OLE M48 [RADIANCE] and OLE M60 [SUNBEAM]). Larger baseline brain volumes were associated with numerically better Symbol Digit Modalities Test scores and lower 3-month confirmed disability progression (CDP) incidence. Annualized TV atrophy ⩽1.0% was associated with lower 3-month CDP. CONCLUSION: This study confirms the sustained efficacy of ozanimod in reducing brain atrophy rates for up to 7 years. Brain volume preservation was associated with faster cognitive processing speed and slower physical disability progression.

• Klíčová slova
• MRI, Multiple sclerosis, Symbol Digit Modalities Test, confirmed disability progression, sphingosine 1-phosphate receptor modulators, thalamus,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Patients with oligodendroglioma have a relatively favourable prognosis. The long-term impacts of the tumour itself and its treatment on health-related quality of life (HRQOL) and cognition remain largely unclear. We investigated associations between treatment and functioning of survivors of oligodendroglioma. METHODS: In this cross-sectional observational study, patients with oligodendroglioma, isocitrate dehydrogenase-mutant and 1p/19q-codeleted, diagnosed ≥5 years ago, were recruited. Patients completed patient-reported outcome measures (EORTC QLQ-C30; BN20; MOS Cognitive Complaints Scale) and cognitive tests (HVLT-R, TMT, COWAT). Associations between HRQOL and cognition outcomes, and clinical variables (time since diagnosis; age at diagnosis; progression; tumour location; treatments delivered; time since treatment; current medication;) were explored with regression analyses. RESULTS: In total, 237 patients M=9.9 years post-diagnosis (sd=4.2, range 5.0-25.8) took part from 33 sites across 9 countries. Clinically relevant levels of impairment were noted in >40% of patients on EORTC QLQ-C30 scales for cognitive functioning (56.1%), emotional functioning (49.8%), fatigue (45.1%), and physical functioning (40.5%). In individuals, cognitive impairment ranged from 17.7% for processing speed to 46.0% for episodic verbal memory (delayed recall). Among other clinical factors such as current use of antiseizure medication or antidepressants, age, disease progression, time since diagnosis and time since treatment, and radiotherapy treatment (ever received) was linked to HRQOL and cognitive functioning outcomes (post-hoc analyses for cumulative radiotherapy dose: not significant). CONCLUSIONS: In oligodendroglioma survivors, HRQOL and cognitive impairment are prevalent even years into follow-up. Supportive care and rehabilitation should be prioritized to mitigate these challenges and improve daily functioning. TRIAL REGISTRATION: NCT04708548.

• Klíčová slova
• cognition, health-related quality of life, low-grade glioma, oligodendroglioma, survivorship,
• Publikační typ
• časopisecké články MeSH

This study evaluates effects of a mixture of 29 chemicals in pregnancy (organochlorine compounds, per - and polyfluoroalkyl substances, phenols, and phthalates) on cognitive abilities (working memory, attentional function, visuomotor attention, cognitive flexibility, verbal and non-verbal intelligence, information processing speed, risky decision making) and fine motor function in childhood. Data from over 2000 mothers and their children that take part in the INfancia y Medio Ambiente in Spain were analyzed. Quantile-based g-computation estimated joint effects of chemical mixtures on the outcomes, adjusting for confounders and using inverse probability weights to mitigate selection bias. The overall mixture of chemicals was linked to lower visuomotor attention (i.e., slower response time, +0.2 min, 95 % CI 0.0 to 0.4 for the second; +0.4 min, 95 % CI 0.0 to 0.8 for the third; and +0.7 min, 95 % CI 0.0 to 1.3 for the fourth quartile, relative to the first quartile). Counterintuitively, the overall mixture of chemicals was related to higher verbal intelligence (+1.5 points, 95 % CI 0.1 to 3.0 for the second; +3.0 points, 95 % CI 0.1 to 6.0 for the third; and +4.6 points, 95 % CI 0.2 to 9.0 for the fourth quartile, relative to the first quartile). However, neither of these associations survived multiple testing correction. Our study does not provide strong evidence that prenatal exposure to a mixture of organochlorine compounds, per - and polyfluoroalkyl substances, phenols, and phthalates affects cognitive abilities or fine motor function in childhood.

• Klíčová slova
• Chemical mixtures, Cognitive abilities, Fine motor function, Neurodevelopment, Prenatal exposures,
• Publikační typ
• časopisecké články MeSH

Over the past three turbulent decades, research has profoundly reshaped our understanding of chronic Toxoplasma gondii infection-traditionally regarded as harmless in immunocompetent individuals-unveiling its surprising impact on human health, performance, and behavior. This review emphasizes the effects of chronic Toxoplasma infection on physical and mental health, cognitive performance, and behavioral changes, highlighting key findings from studies investigating these domains, with a particular focus on both ultimate and proximate mechanisms underlying the observed effects. To this end, the primary focus will be on human studies; however, animal model studies will also be thoroughly considered when necessary and appropriate, to provide context and additional important information. Research demonstrates that chronic Toxoplasma infection may contribute to a broad spectrum of physical health issues. Ecological studies have revealed correlations between toxoplasmosis prevalence and increased morbidity and mortality from various conditions, including cardiovascular diseases, neurological disorders, and certain cancers. Large-scale cross-sectional studies have further shown that infected individuals report a higher incidence of numerous health complaints and diagnosed diseases, suggesting a significant impact on overall physical well-being. In addition to physical health, lifelong Toxoplasma infection (subclinical toxoplasmosis) has been implicated in cognitive impairments and behavioral changes. Studies have reported associations between infection and poorer performance in areas such as reaction time, processing speed, working memory, and executive function. Many of these behavioral changes likely relate to worsened health and a shift towards a "fast life history strategy." These cognitive deficits can have significant implications for daily functioning and performance. Furthermore, the role of Toxoplasma infection in the development or exacerbation of mental health disorders has been extensively investigated. Meta-analyses, ecological studies, and large-scale observational studies have demonstrated associations between Toxoplasma infection and an increased risk of disorders such as schizophrenia and obsessive-compulsive disorder. While the precise mechanisms underlying these associations remain under investigation, research suggests that neuroinflammation and alterations in neurotransmitter systems are likely to play a role. Far from being harmless, subclinical toxoplasmosis is increasingly recognized as a hidden factor influencing human health, behavior, and cognitive performance-with implications that extend well beyond the individual to public health at large. Further research is warranted to elucidate the complex interplay between Toxoplasma infection, host physiology, and the development of various physical, cognitive, behavioral, and mental health conditions.

• Klíčová slova
• OCD, RhD, Rhesus D antigen, autism, evolution, intelligence, manipulation hypothesis, mental health, parasite, schizophrenia, subclinical toxoplasmosis, testosterone,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The present functional magnetic resonance imaging (fMRI) study investigated neural correlates of switching between task-processing and periods of rest in a conventional ON-OFF block-design in patients with auditory verbal hallucinations (AVHs) and healthy controls. It has been proposed that auditory hallucinations are a failure of top-down control of bottom-up perceptual processes which could be due to aberrant up- and down regulation of brain networks. A version of the Eriksen Flanker task was used to assess cognitive flexibility and conflict control. BOLD fMRI with alternating blocks of task engagement and rest was collected using a 3T MR scanner. The objective of the study was to explore how patients would dynamically modulate relevant brain networks in response to shifting environmental demands, while transitioning from a resting state to active task-processing. Analysis of performance data found significant behavioral effects between the groups, where AVH patients performed the Flanker task significantly less accurately and with longer reaction times (RTs) than the healthy control group, indicating that AVH patients displayed reduced top-down guided conflict control. A network connectivity analysis of the fMRI data showed that both groups recruited similar networks related to task-present and task-absent conditions. However, the controls displayed increased network variability across task-present and task-absent conditions. This would indicate that the controls were better at switching between networks and conditions when demands changed from task-present to task-absent, with the consequence that they would perform the Flanker task better than the AVH patients.

• MeSH
• dospělí MeSH
• halucinace * patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mapování mozku MeSH
• mladý dospělý MeSH
• mozek * patofyziologie   MeSH
• nervová síť * patofyziologie   MeSH
• plnění a analýza úkolů MeSH
• reakční čas MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Cognitive impairment is a well-recognized symptom of multiple sclerosis (MS) that can manifest early in the disease course. Deficits in cognitive function can have a major impact on daily life. However, cognitive decline is often under-examined in clinical trials and clinical practice due to lack of adequate data. The objective of this study was to examine the longitudinal effect of ocrelizumab vs interferon beta (IFNβ)-1a on cognitive impairment in 2 phase 3 studies in relapsing MS (RMS). METHODS: The pooled population of participants with RMS (n = 1656) from the OPERA I/II clinical trials received subcutaneous IFNβ-1a (44 μg; n = 829) 3 times weekly or intravenous ocrelizumab (600 mg; n = 827) every 24 weeks. Cognition was assessed with a Symbol Digit Modalities Test (SDMT), administered in written or oral form according to each site investigator's choice, that primarily measured cognitive processing speed at baseline and every 12 weeks until the end of the double-blind treatment (96 weeks). Treatment effects were investigated based on longitudinal linear models for the change from baseline in SDMT and Cox regression for the time to 12- or 24-week confirmed decline of ≥4 points. RESULTS: Among the participants with an SDMT assessment at baseline and ≥1 postbaseline time point (IFNβ-1a, n = 749; ocrelizumab, n = 766), ocrelizumab treatment was associated with a greater mean SDMT improvement over 96 weeks than IFNβ-1a treatment (5.4 [95 % CI, 4.4-6.5] vs 4.0 [95 % CI, 3.0-5.1]; adjusted mean difference, 1.4 [95 % CI, 0.05-2.72]; P = 0.042). The risk of a clinically meaningful SDMT decline (≥4 points) was lower for those treated with ocrelizumab for both ≥12 weeks (IFNβ-1a, 18.4 %; ocrelizumab, 12.7 %; hazard ratio, 0.63 [95 % CI, 0.47-0.85]; P = 0.003) and ≥24 weeks (IFNβ-1a, 12.9 %; ocrelizumab, 7.9 %; HR, 0.57 [95 % CI, 0.39-0.82]; P = 0.003). CONCLUSION: Ocrelizumab treatment resulted in better cognitive outcomes as measured by SDMT in participants with RMS compared with IFNβ-1a treatment. However, methodological limitations need to be considered when interpreting these data. CLINICALTRIALS: gov: NCT01247324, NCT01412333.

• Klíčová slova
• Cognitive impairment, DMT, Multiple sclerosis, Ocrelizumab, SDMT,
• MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• humanizované monoklonální protilátky * farmakologie   aplikace a dávkování   terapeutické užití   MeSH
• imunologické faktory * farmakologie   aplikace a dávkování   terapeutické užití   MeSH
• interferon beta 1a * farmakologie   terapeutické užití   aplikace a dávkování   MeSH
• kognitivní dysfunkce * etiologie   farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• relabující-remitující roztroušená skleróza * farmakoterapie   komplikace   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• humanizované monoklonální protilátky * MeSH
• imunologické faktory * MeSH
• interferon beta 1a * MeSH
• ocrelizumab MeSH Prohlížeč

BACKGROUND AND PURPOSE: Cognitive impairment (CI) in multiple sclerosis (MS) is associated with bidirectional changes in resting-state centrality measures. However, practicable functional magnetic resonance imaging (fMRI) biomarkers of CI are still lacking. The aim of this study was to assess the graph-theory-based degree rank order disruption index (kD) and its association with cognitive processing speed as a marker of CI in patients with MS (PwMS) in a secondary cross-sectional fMRI analysis. METHODS: Differentiation between PwMS and healthy controls (HCs) using kD and its correlation with CI (Symbol Digit Modalities Test) was compared to established imaging biomarkers (regional degree, volumetry, diffusion-weighted imaging, lesion mapping). Additional associations were assessed for fatigue (Fatigue Scale for Motor and Cognitive Functions), gait and global disability. RESULTS: Analysis in 56 PwMS and 58 HCs (35/27 women, median age 45.1/40.5 years) showed lower kD in PwMS than in HCs (median -0.30/-0.06, interquartile range 0.55/0.54; p = 0.009, Mann-Whitney U test), yielding acceptable yet non-superior differentiation (area under curve 0.64). kD and degree in medial prefrontal cortex (MPFC) correlated with CI (kD/MPFC Spearman's ρ = 0.32/-0.45, p = 0.019/0.001, n = 55). kD also explained fatigue (ρ = -0.34, p = 0.010, n = 56) but neither gait nor disability. CONCLUSIONS: kD is a potential biomarker of CI and fatigue warranting further validation.

• Klíčová slova
• biomarkers, cognitive processing speed, fMRI, fatigue, multiple sclerosis,
• MeSH
• dospělí MeSH
• kognitivní dysfunkce etiologie   patofyziologie   diagnostické zobrazování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• průřezové studie MeSH
• roztroušená skleróza * komplikace   diagnostické zobrazování   patofyziologie   MeSH
• rychlost zpracování MeSH
• únava * patofyziologie   etiologie   diagnostické zobrazování   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Aging populations face significant cognitive challenges, particularly in working memory (WM). Transcranial alternating current stimulation (tACS) offer promising avenues for cognitive enhancement, especially when inspired by brain physiology. This study (NCT04986787) explores the effect of multifocal tACS on WM performance in healthy older adults, focusing on fronto-parietal network modulation. Individualized physiology-inspired tACS applied to the fronto-parietal network was investigated in two blinded cross-over experiments. The first experiment involved monofocal/bifocal theta-tACS to the fronto-parietal network, while in the second experiment cross-frequency theta-gamma interactions between these regions were explored. Participants have done online WM tasks under the stimulation conditions. Network connectivity was assessed via rs-fMRI and multichannel electroencephalography. Prefrontal monofocal theta tACS modestly improved WM accuracy over sham (d = 0.30). Fronto-parietal stimulation enhanced WM task processing speed, with the strongest effects for bifocal in-phase theta tACS (d = 0.41). Cross-frequency stimulations modestly boosted processing speed with or without impairing task accuracy depending on the stimulation protocol. This research adds to the understanding of physiology-inspired brain stimulation for cognitive enhancement in older subjects.

• Klíčová slova
• Cognition, Electric field modelling, Healthy aging, Multifocal, Neuroimaging, Orchestrated brain stimulation, Systems neuroscience, Working memory, tACS,
• Publikační typ
• časopisecké články MeSH

Acute and transient psychotic disorder (ATPD) is characterized by acute onset of psychotic symptoms and early recovery. Contrastingly, schizophrenia (SZ) is a chronic mental disorder characterized by impaired functioning including a deficit in cognition. In SZ, the cognitive deficit is among the core symptoms, but in ATPDs, the existing evidence brings mixed results. Our primary aim was to compare three core cognitive domains (executive functioning/abstraction, speed of processing and working memory) of patients diagnosed with ATPD and SZ over a 12-month period. Moreover, we explored how these diagnostic subgroups differed in their clinical characteristics. We recruited 39 patients with a diagnosis of SZ and 31 with ATPD with schizophrenic symptoms. All patients completed clinical and neuropsychological assessments. At baseline, we used a one-way ANCOVA model with a group as the between-subjects factor. Mixed-model repeated-measures ANOVAs with time as the within-subjects factor and group as the between-subjects factor were run to test the overtime differences. At baseline, we did not find any differences in cognition - with sex, education and age as covariates - between ATPDs and SZ. After one year, all patients showed an improvement in all three domains, however, there were no significant overtime changes between ATPDs and SZ. Regarding clinical profiles, ATPDs demonstrated less severe psychopathology and better functioning compared to SZ both at baseline and after 12 months. The medication dosage differed at retest, but not at baseline between the groups. Our findings suggest clinical differences and a similar trajectory of cognitive performance between these diagnostic subgroups.

• Klíčová slova
• Acute and transient psychotic disorder, Brief psychotic disorder, Cognition, First-episode, Schizophrenia,
• Publikační typ
• časopisecké články MeSH

Given the key roles of the cerebellum in motor, cognitive, and affective operations and given the decline of brain functions with aging, cerebellar circuitry is attracting the attention of the scientific community. The cerebellum plays a key role in timing aspects of both motor and cognitive operations, including for complex tasks such as spatial navigation. Anatomically, the cerebellum is connected with the basal ganglia via disynaptic loops, and it receives inputs from nearly every region in the cerebral cortex. The current leading hypothesis is that the cerebellum builds internal models and facilitates automatic behaviors through multiple interactions with the cerebral cortex, basal ganglia and spinal cord. The cerebellum undergoes structural and functional changes with aging, being involved in mobility frailty and related cognitive impairment as observed in the physio-cognitive decline syndrome (PCDS) affecting older, functionally-preserved adults who show slowness and/or weakness. Reductions in cerebellar volume accompany aging and are at least correlated with cognitive decline. There is a strongly negative correlation between cerebellar volume and age in cross-sectional studies, often mirrored by a reduced performance in motor tasks. Still, predictive motor timing scores remain stable over various age groups despite marked cerebellar atrophy. The cerebello-frontal network could play a significant role in processing speed and impaired cerebellar function due to aging might be compensated by increasing frontal activity to optimize processing speed in the elderly. For cognitive operations, decreased functional connectivity of the default mode network (DMN) is correlated with lower performances. Neuroimaging studies highlight that the cerebellum might be involved in the cognitive decline occurring in Alzheimer's disease (AD), independently of contributions of the cerebral cortex. Grey matter volume loss in AD is distinct from that seen in normal aging, occurring initially in cerebellar posterior lobe regions, and is associated with neuronal, synaptic and beta-amyloid neuropathology. Regarding depression, structural imaging studies have identified a relationship between depressive symptoms and cerebellar gray matter volume. In particular, major depressive disorder (MDD) and higher depressive symptom burden are associated with smaller gray matter volumes in the total cerebellum as well as the posterior cerebellum, vermis, and posterior Crus I. From the genetic/epigenetic standpoint, prominent DNA methylation changes in the cerebellum with aging are both in the form of hypo- and hyper-methylation, and the presumably increased/decreased expression of certain genes might impact on motor coordination. Training influences motor skills and lifelong practice might contribute to structural maintenance of the cerebellum in old age, reducing loss of grey matter volume and therefore contributing to the maintenance of cerebellar reserve. Non-invasive cerebellar stimulation techniques are increasingly being applied to enhance cerebellar functions related to motor, cognitive, and affective operations. They might enhance cerebellar reserve in the elderly. In conclusion, macroscopic and microscopic changes occur in the cerebellum during the lifespan, with changes in structural and functional connectivity with both the cerebral cortex and basal ganglia. With the aging of the population and the impact of aging on quality of life, the panel of experts considers that there is a huge need to clarify how the effects of aging on the cerebellar circuitry modify specific motor, cognitive, and affective operations both in normal subjects and in brain disorders such as AD or MDD, with the goal of preventing symptoms or improving the motor, cognitive, and affective symptoms.

• Klíčová slova
• Affective, Aging, Alzheimer’s Disease, Cerebellum, Cognitive, Motor,
• MeSH
• depresivní porucha unipolární * MeSH
• dospělí MeSH
• konsensus MeSH
• kvalita života MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• mozeček patologie   MeSH
• průřezové studie MeSH
• senioři MeSH
• stárnutí MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH