Search

Impaired kidney function is associated with structural brain changes and cognitive dysfunction. In the aging kidney, hemodynamic and structural alterations reduce the glomerular filtration rate (eGFR). Little is known about differences between men and women regarding decline of kidney function and brain damage. In this community-based study, we assessed associations between the eGFR, focal and diffuse brain abnormalities and cognitive functions. Sex-specific effects were analyzed by interaction terms eGFR x sex on brain structure and cognition. Interactive effects were assessed using mixed-models -stratified by sex. Overall, 196 women and 129 men (median age 68 years and mean eGFR 73.8±14.9 ml/min/1.73m 2 ) were included. Significant associations existed between eGFR and cortical volume (β: 1.53E-04; SE: 6.72E-05; p=0.023 for neocortex). Sex exerted a significant interactive effect. Only in men, eGFR related to cortical volumes of all lobes and of deep gray matter structures (p= 0.001 for total gray matter, p=0.0004 for neocortex). In the whole group eGFR was not associated with cognition, but men with lower eGFR performed worse on tests for executive function, which, after FDR correction, was not significant. We conclude, that in community-dwelling middle-aged and elderly individuals, reduced eGFR relates to brain volume loss in men but not in women.

Objective: To investigate the effects of EEG-based neurofeedback training, in which one can learn to self-regulate one's own brain activity, on cognitive function in patients with multiple sclerosis (pwMS)., Methods: Fourteen pwMS performed ten neurofeedback training sessions within 3-4 weeks at home using a tele-rehabilitation system. The aim of the neurofeedback training was to increase voluntarily the sensorimotor rhythm (SMR, 12-15 Hz) in the EEG over central brain areas by receiving visual real-time feedback thereof. Cognitive function was assessed before and after all neurofeedback training sessions using a comprehensive standardized neuropsychological test battery., Results: Half of the pwMS (N = 7) showed cognitive improvements in long-term memory and executive functions after neurofeedback training. These patients successfully learned to self-regulate their own brain activity by means of neurofeedback training. The other half of pwMS (N = 7) did neither show any cognitive changes when comparing the pre- and post-assessment nor were they able to modulate their own brain activity in the desired direction during neurofeedback training., Conclusions: Data from this interventional study provide first preliminary evidence that successful self-regulation of one's own brain activity may be associated with cognitive improvements in pwMS., Significance: These promising results should stimulate further studies. Neurofeedback might be a promising and alternative tool for future cognitive rehabilitation., (Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: Cognitive dysfunction is frequent in multiple sclerosis (MS), and its relationship with cognitive reserve (CR) has been investigated in several studies with conflicting results. In this meta-analysis, we here sought to determine the relationship between CR and cognition in MS patients and to ascertain whether demographic or clinical variables could moderate the above-mentioned relationship., Method: We searched three electronic databases for studies assessing the relationship between CR and performance in 6 cognitive domains or processes (verbal and spatial memory, attention, processing speed, verbal fluency, inhibitory control). The initial literature search yielded 1,452 articles; 245 full-texts were evaluated, and 18 studies were entered into the meta-analysis. Mean weighted effect sizes (ES) were calculated using Hedges' g. Sensitivity analyses and examinations of funnel plots served to reduce heterogeneity., Results: A total number of 1,903 MS patients were included, analyzing each aspect of cognition separately. ES for the relationship between CR and cognition were significant (except for verbal fluency) and moderate. After applying specific techniques to reduce heterogeneity, the verbal fluency ES became significant. Metaregression analysis revealed that older age and female sex increased the ES for attention and verbal memory outcomes., Conclusions: High levels of CR were associated with better cognitive task performance in verbal and spatial memory, attention, processing speed, verbal fluency, and inhibitory control. The results indirectly emphasize the value of early cognitive assessments of cognitive status and CR levels to enable timely initiation of cognitive interventions to increase CR in MS in patients with low levels of CR. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Despite its functional importance and well known clinical impact in Multiple Sclerosis (MS), the cerebellum has only received significant attention over the past few years. It is now established that the cerebellum plays a key role not only in various sensory-motor networks, but also in cognitive-behavioural processes, domains primarily affected in patients with MS. Evidence from histopathological and magnetic resonance imaging (MRI) studies on cerebellar involvement in MS is increasingly available, however linking these pathological findings with clinical dysfunction remains challenging. There are promising advances in technology that are likely to improve the detection of pathological changes within the cerebellum, which may elucidate how pathology relates to disability., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To quantify the magnitude of deficits in theory of mind (ToM) and facial emotion recognition among patients with multiple sclerosis (MS) relative to healthy controls., Methods: An electronic database search of Ovid MEDLINE, PsycINFO, and Embase was conducted from inception to April 1, 2016. Eligible studies were original research articles published in peer-reviewed journals that examined ToM or facial emotion recognition among patients with a diagnosis of MS and a healthy control comparison group. Data were independently extracted by 2 authors. Effect sizes were calculated using Hedges g., Results: Twenty-one eligible studies were identified assessing ToM (12 studies) and/or facial emotion recognition (13 studies) among 722 patients with MS and 635 controls. Deficits in both ToM (g = -0.71, 95% confidence interval [CI] -0.88 to -0.55, p < 0.001) and facial emotion recognition (g = -0.64, 95% CI -0.81 to -0.47, p < 0.001) were identified among patients with MS relative to healthy controls. The largest deficits were observed for visual ToM tasks and for the recognition of negative facial emotional expressions. Older age predicted larger emotion recognition deficits. Other cognitive domains were inconsistently associated with social cognitive performance., Conclusions: Social cognitive deficits are an overlooked but potentially important aspect of cognitive impairment in MS with potential prognostic significance for social functioning and quality of life. Further research is required to clarify the longitudinal course of social cognitive dysfunction, its association with MS disease characteristics and neurocognitive impairment, and the MS-specific neurologic damage underlying these deficits., (© 2016 American Academy of Neurology.)

Objectives: The objectives of this paper are to compare in a multicenter setting patterns of regional cortical thickness in patients with relapsing-remitting multiple sclerosis (RRMS) and cognitive impairment (CI) and those cognitively preserved (CP), and explore the relationship between cortical thinning and cognitive performance., Methods: T1-weighted isotropic brain scans were collected at 3T from seven European centers in 60 RRMS patients and 65 healthy controls (HCs). Patients underwent clinical and neuropsychological examinations. Cortical thickness (CTh) measures were calculated using FreeSurfer (failing in four) and both lobar and vertex-based general linear model (GLM) analyses were compared between study groups., Results: Twenty (36%) MS patients were classified as CI. Mean global CTh was smaller in RRMS patients compared to HCs (left 2.43 vs. 2.53 mm, right 2.44 vs. 2.54 mm, p < 0.001). Multivariate GLM regional analysis showed significantly more temporal thinning in CI compared to CP patients. Verbal memory scores correlated to regional cortical thinning in the insula whereas visual memory scores correlated to parietal thinning., Conclusions: This multicenter study showed mild global cortical thinning in RRMS. The extent of thinning is less pronounced than previously reported. Only subtle regional differences between CI and CP patients were observed, some of which related to specific cognitive domains., (© The Author(s), 2015.)

Background: Extrapolations from previous cross-sectional fMRI studies suggest cerebral functional changes with progression of Multiple Sclerosis (MS), but longitudinal studies are scarce. We assessed brain activation changes over time in MS patients using a cognitive fMRI paradigm and examined correlations with clinical and cognitive status and brain morphology., Methods: 13 MS patients and 15 healthy controls (HC) underwent MRI including fMRI (go/no-go task), neurological and neuropsychological exams at baseline (BL) and follow-up (FU; minimum 12, median 20 months). We assessed estimates of and changes in fMRI activation, total brain and subcortical grey matter volumes, cortical thickness, and T2-lesion load. Bland-Altman (BA) plots served to assess fMRI signal variability., Results: Cognitive and disability levels remained largely stable in the patients. With the fMRI task, both at BL and FU, patients compared to HC showed increased activation in the insular cortex, precuneus, cerebellum, posterior cingulate cortex, and occipital cortex. At BL, patients vs. HC also had lower caudate nucleus, thalamus and putamen volumes. Over time, patients (but not HC) demonstrated fMRI activity increments in the left inferior parietal lobule. These correlated with worse single-digit-modality test (SDMT) performance. BA-plots attested to reproducibility of the fMRI task. In the patients, the right caudate nucleus decreased in volume which again correlated with worsening SDMT performance., Conclusions: Given preserved cognitive performance, the increased activation at BL in the patients may be viewed as largely adaptive. In contrast, the negative correlation with SDMT performance suggests increasing parietal activation over time to be maladaptive. Several areas with purported relevance for cognition showed decreased volumes at BL and right caudate nucleus volume decline correlated with decreasing SDMT performance. This highlights the dynamics of functional changes and the strategic importance of specific brain areas for cognitive processes in MS.

Background: Lesion dissemination in time and space represents a key feature and diagnostic marker of multiple sclerosis (MS). The correlation between magnetic resonance imaging (MRI) lesion load and disability is only modest, however. Strategic lesion location might at least partially account for this 'clinico-radiologic paradox'., Objectives: Here we used a non-parametric permutation-based approach to map lesion location probability based on MS lesions identified on T2-weighted MRI. We studied 121 patients with clinically isolated syndrome, relapsing-remitting or secondary progressive MS and correlated these maps to assessments of neurologic and cognitive functions., Results: The Expanded Disability Status Scale correlated with bilateral periventricular lesion location (LL), and sensory and coordination functional system deficits correlated with lesion accumulation in distinct anatomically plausible regions, i.e. thalamus and middle cerebellar peduncule. Regarding cognitive performance, decreased verbal fluency correlated with left parietal LL comprising the putative superior longitudinal fascicle. Delayed spatial recall correlated with &#95;amygdalar, &#95;left frontal and parietal LL. Delayed selective reminding correlated with bilateral frontal and temporal LL. However, only part of the spectrum of cognitive and neurological problems encountered in our cohort could be explained by specific lesion location., Conclusions: Lesion probability mapping supports the association of specific lesion locations with symptom development in MS, but only to limited extent.

Background: Cognitive deficits are frequent in multiple sclerosis (MS) and have been associated with morphologic brain changes. Less information exists on their extent and relation to MRI findings in clinically isolated syndrome (CIS). It is also unclear if structural changes as detected by magnetization transfer (MT) imaging may provide an additional explanation for cognitive dysfunction., Objective: To analyse the extent of cognitive deficits and their relation to MRI metrics including MT imaging in CIS compared to relapsing-remitting MS (RRMS)., Methods: Forty-four CIS and 80 RRMS patients underwent the Brief Repeatable Battery of Neuropsychological Tests (BRB-N) and a 3 T MRI scan., Results: BRB-N subtests revealed similar results in CIS and RRMS. Impaired mental processing speed was most prevalent in both groups (CIS 13.6%; RRMS 16.3%) and thus served for correlation with MRI metrics. Using stepwise linear regression analyses, the strongest predictor for decreased mental processing speed was normalized cortex volume (p < 0.001) followed by T₂-lesion load (p < 0.05) in RRMS, whereas cortical MT ratio was the only MRI parameter associated with decreased mental processing speed in CIS (p < 0.005)., Conclusion: Cognitive dysfunction occurs in CIS in a pattern similar to RRMS, with impaired mental processing speed being most prevalent. Cortical MT-ratio changes may be an early sign for tissue changes related to impaired mental processing speed in CIS while this association shifts to increased signs of cortical atrophy and lesion load in RRMS.

Objective: We explored cognitive impairment in metabolic syndrome in relation to brain magnetic resonance imaging (MRI) findings., Research Design and Methods: We studied 819 participants free of clinical stroke and dementia of the population-based Austrian Stroke Prevention Study who had undergone brain MRI, neuropsychological testing, and a risk factor assessment relevant to National Cholesterol Education Program Adult Treatment Panel III criteria-defined metabolic syndrome. High-sensitivity C-reactive protein (hs-CRP) was also determined., Results: Of 819 subjects, 232 (28.3%) had metabolic syndrome. They performed worse than those without metabolic syndrome on cognitive tests assessing memory and executive functioning after adjustment for possible confounders. Stratification by sex demonstrated that metabolic syndrome was related to cognitive dysfunction in men but not in women. Only in men was an increasing number of metabolic syndrome components associated with worse cognitive performance. MRI showed no significant differences in focal ischemic lesions and brain volume between subjects with and without metabolic syndrome, and MRI abnormalities failed to explain impaired cognition. Cognitive performance was most affected in male subjects with metabolic syndrome who also had high hs-CRP levels., Conclusions: Metabolic syndrome exerts detrimental effects on memory and executive functioning in community-dwelling subjects who have not had a clinical stroke or do not have dementia. Men are more affected than women, particularly if they have high inflammatory markers. MRI-detected brain abnormalities do not play a crucial role in these relationships.

We performed a prospective multi-centre study using functional magnetic resonance imaging (fMRI) to better characterize the relationships between clinical expression and brain function in patients with multiple sclerosis (MS) at eight European sites (56 MS patients and 60 age-matched, healthy controls). Patients showed greater task-related activation bilaterally in brain regions including the pre- and post-central, inferior and superior frontal, cingulate and superior temporal gyri and insula (P < 0.05, all statistics corrected for multiple comparisons). Both patients and healthy controls showed greater brain activation with increasing age in the ipsilateral pre-central and inferior frontal gyri (P < 0.05). Patients, but not controls, showed greater brain activation in the anterior cingulate gyrus and the bilateral ventral striatum (P < 0.05) with less hand dexterity. An interaction between functional activation changes in MS and age was found. This large fMRI study over a broadly selected MS patient population confirms that movement for patients demands significantly greater cognitive 'resource allocation' and suggests age-related differences in brain responses to the disease. These observations add to evidence that brain functional responses (including potentially adaptive brain plasticity) contribute to modulation of clinical expression of MS pathology and demonstrate the feasibility of a multi-site functional MRI study of MS.

Background and Purpose: Leukoaraiosis is used interchangeably with the term white matter lesions on MRI and seen to some degree in more than half of the routine scans in older persons. Clinicians often struggle to explain the implications of these findings to their patients. Recent data on the progression rate of ischemic white matter damage and its cognitive consequences may help in patient counseling and have implications on treatment trials in vascular cognitive impairment. Summary of Review-Leukoaraiosis progresses over time. Its extent at baseline is an important predictor for the subsequent rate of lesion progression. Subjects with punctate abnormalities on MRI have a low tendency for progression, individuals with early confluent and confluent changes tend to progress rapidly. Differences in measurement methods and cohort composition make it difficult to compare progression rates reported by different studies. Nevertheless, in community-dwelling cohorts, white matter lesions volume increased by as much as one quarter per year in subjects with confluent abnormalities at baseline. Progression of leukoaraiosis relates to cognitive decline, but this association is complex and modulated by other morphological factors like brain atrophy., Conclusions: Evidence for rapid progression of widespread leukoaraiosis and the associated cognitive decline in domains particularly affected by cerebral small vessel disease has set the stage for exploratory clinical trials in vascular cognitive impairment using white matter lesions progression as a surrogate marker.

Subcortical vascular cognitive impairment is caused by lacunes and widespread ischemic white matter damage which closely resembles white matter abnormalities seen in multiple sclerosis. Recent evidence suggests that the progression rate of ischemic white matter lesions on MRI is very similar to that observed in multiple sclerosis. Consequently, it has been proposed to use MRI for monitoring disease activity not only in multiple sclerosis but also in vascular dementia trials. There is first evidence from magnetization transfer imaging studies that other than in MS normal appearing white matter is not affected in cerebral small vessel disease. This contrasts the hypothesis that ischemic white matter damage extends far beyond changes visible on conventional MR. The cognitive consequences of both diseases are strikingly similar which is at least partly caused by damage to frontal-subcortical circuits. Involvement of these common functional anatomical structures and their modulatory transmitter systems has now led to common interventional approaches such as the use of cholinesterase inhibitors.

Background and Purpose: Cognitive impairment is a core symptom in multiple sclerosis (MS). Damage to normal appearing white matter (NAWM) is likely involved. We sought to determine if greater myelin heterogeneity in NAWM is associated with decreased cognitive performance in MS., Methods: A total of 27 participants with MS and 13 controls matched for age, sex, and education underwent myelin water imaging (MWI) from which the myelin water fraction (MWF) was calculated. Corpus callosum, superior longitudinal fasciculus, and cingulum were chosen as regions of interest (ROIs) a priori based on their involvement in MS-related cognitive impairment. Cognitive performance was assessed using the Symbol Digit Modalities Test (SDMT). Pearson ́s product moment correlations were performed to assess relationships between cognitive performance and myelin heterogeneity (variance of MWF within an ROI)., Results: In MS, myelin heterogeneity in all three ROIs was significantly associated with performance on the SDMT. These correlations ranged from moderate (r = -.561) to moderately strong (r = -.654) and were highly significant (P values ranged from .001 to .0002). Conversely, myelin heterogeneity was not associated with SDMT performance in controls in any ROI (P > .108)., Conclusion: Increased myelin heterogeneity in NAWM is associated with decreased cognitive processing speed performance in MS., (© 2019 by the American Society of Neuroimaging.)

Barbara Landsmann,1,2 Daniela Pinter,2 Eva Pirker,1,2 Gerald Pichler,3 Walter Schippinger,3 Elisabeth M Weiss,1 Gabriel Mathie,2 Thomas Gattringer,2 Franz Fazekas,2 Christian Enzinger2,4 1Institute of Psychology, University of Graz, Graz, Austria; 2Department of Neurology, Medical University of Graz, Graz, Austria; 3Albert Schweitzer Clinic Graz, Graz, Austria; 4Division of Neuroradiology, Department of Radiology, Medical University of Graz, Graz, Austria Purpose: Previous studies demonstrated changes in sensorimotor network activation over time after stroke that have been interpreted as partly compensatory. Locomotor and balance trainings may improve both mobility and cognition even in chronic stroke and thereby impact on cerebral activation patterns. We here aimed at testing these assumptions in an exploratory study to inform subsequent larger intervention studies. Patients and methods: Eight patients (73.3±4.4 years) with a chronic lacunar stroke (mean interval 3.7 years after the acute event with a range from 2 to 4 years) and residual leg paresis leading to gait disturbance received a guided 5-week training focusing on mobility, endurance, and coordination. Before and afterward, they underwent clinical, neuropsychological, and gait assessments and brain MRI at 3 T including a functional ankle movement paradigm. Sixteen healthy controls (HCs; 68.8±5.4 years) followed the same protocol without intervention. Results: After training, patients had improved in mobility, memory, and delayed recall of memory. While cerebral activations in HC remained completely unaltered, patients showed increased activations in the right precentral gyrus, the right and left superior frontal gyri, and the right frontal lobe, with bipedal ankle movements after training. Conclusion: In this exploratory study of chronic stroke, we found not only significant effects of physical training on mobility but also distinct aspects of cognition already with a small number of highly selected patients. These improvements were paralleled by alterations in cerebral activity possibly reflecting neuronal plasticity. Larger studies including randomization are needed. Keywords: mobility, cognition, lacunar stroke, training, rehabilitation, neuronal plasticity

Background and purpose: Cognitive impairment is a common sequel of recent small subcortical infarction (RSSI) and might be negatively affected by preexisting cerebral small vessel disease (SVD). We investigated whether the course of cognitive function in patients with RSSI is influenced by the severity of white matter hyperintensities (WMH), an important imaging feature of SVD. Methods: Patients with magnetic resonance imaging (MRI)‐proven single RSSI were tested neuropsychologically concerning global cognition, processing speed, attention, and set‐shifting. Deep and periventricular WMH severity was assessed using the Fazekas scale, and total WMH lesion volume was calculated from T1‐weighted MRI images. We compared baseline function and course of cognition 15 months after the acute event in patients with absent, mild, and moderate‐to‐severe WMH. Results: The study cohort comprised 82 RSSI patients (mean age: 61 ± 10 years, 23% female). At baseline, 40% had cognitive impairment (1.5 standard deviations below standardized mean), and deficits persisted in one‐third of the sample after 15 months. After age correction, there were no significant differences in set‐shifting between WMH groups at baseline. However, although patients without WMH (deep: p < 0.001, periventricular: p = 0.067) or only mild WMH (deep: p = 0.098, periventricular: p = 0.001) improved in set‐shifting after 15 months, there was no improvement in patients with moderate‐to‐severe WMH (deep: p = 0.980, periventricular: p = 0.816). Baseline total WMH volume (p = 0.002) was the only significant predictor for attention 15 months poststroke. Conclusions: This longitudinal study demonstrates that preexisting moderate‐to‐severe WMH negatively affect the restoration of cognitive function after RSSI, suggesting limited functional reserve in patients with preexisting SVD. [ABSTRACT FROM AUTHOR]

Background and purpose: Information on the prevalence and course of post‐stroke cognitive impairment in young stroke patients is limited. The aim was to assess a consecutive sample of acute young ischaemic stroke patients (18–55 years) for the presence and development of neuropsychological deficits. Methods: Patients prospectively underwent a comprehensive clinical and cognitive assessment, examining general cognitive function, processing speed, attention, flexibility/executive function and word fluency within the first 3 weeks after hospital admission (median assessment at day 6) and at a 3 months' follow‐up (FU). Cognitive dysfunction was defined in comparison to age‐standardized published norms. Results: At baseline (N = 114), deficits were highly prevalent in processing speed (56.0%), flexibility/executive function (49.5%), attention (46.4%) and general cognitive function (42.1%). These frequencies were comparable for those with FU assessment (N = 87). In most domains, cognitive performance improved within 3 months, except for word fluency. However, in about one‐third of patients, cognitive deficits (as defined by 1.5 standard deviations below the standardized mean) were still present 3 months after stroke. At FU, 44.0% were impaired in the domain flexibility/executive function, 35.0% in processing speed and 30.0% in attention. Conclusions: The high prevalence of cognitive deficits in acute young patients with ischaemic stroke highlights the importance of early post‐stroke cognitive assessment to capture a patient's dysfunction in a comprehensive manner and to offer adequate rehabilitation. The role of factors which promote neuropsychological deficits needs further exploration. [ABSTRACT FROM AUTHOR]

Background: Lesion dissemination in time and space represents a key feature and diagnostic marker of multiple sclerosis (MS). The correlation between magnetic resonance imaging (MRI) lesion load and disability is only modest, however. Strategic lesion location might at least partially account for this ‘clinico-radiologic paradox’.Objectives: Here we used a non-parametric permutation-based approach to map lesion location probability based on MS lesions identified on T2-weighted MRI. We studied 121 patients with clinically isolated syndrome, relapsing–remitting or secondary progressive MS and correlated these maps to assessments of neurologic and cognitive functions.Results: The Expanded Disability Status Scale correlated with bilateral periventricular lesion location (LL), and sensory and coordination functional system deficits correlated with lesion accumulation in distinct anatomically plausible regions, i.e. thalamus and middle cerebellar peduncule. Regarding cognitive performance, decreased verbal fluency correlated with left parietal LL comprising the putative superior longitudinal fascicle. Delayed spatial recall correlated with _amygdalar, _left frontal and parietal LL. Delayed selective reminding correlated with bilateral frontal and temporal LL. However, only part of the spectrum of cognitive and neurological problems encountered in our cohort could be explained by specific lesion location.Conclusions: Lesion probability mapping supports the association of specific lesion locations with symptom development in MS, but only to limited extent. [ABSTRACT FROM AUTHOR]

The Faces Symbol Test (FST) has recently been proposed as a brief and patient-friendly screening instrument for the assessment of cognitive dysfunction in patients with multiple sclerosis (MS). However, in contrast to well-established MS screening tests such as the Paced Auditory Serial Addition Test, the neural correlates of the FST have not been investigated so far. In the present study, we developed a functional MRI (fMRI) version of the FST to provide first data on brain regions and networks involved in this test. A sample of 19 healthy participants completed a version of the FST adapted for fMRI, requiring matching of faces and symbols in a multiple choice test and two further experimental conditions drawing on cognitive subcomponents (face matching and symbol matching). Imaging data showed a differential involvement of a fronto-parieto-occipital network in the three conditions. The most demanding FST condition elicited brain activation patterns related with sustained attention and executive control. These results suggest that the FST recruits brain networks critical for higherorder cognitive functions often impaired in MS patients. [ABSTRACT FROM AUTHOR]

Objectives: The objectives of this paper are to compare in a multicenter setting patterns of regional cortical thickness in patients with relapsing–remitting multiple sclerosis (RRMS) and cognitive impairment (CI) and those cognitively preserved (CP), and explore the relationship between cortical thinning and cognitive performance. Methods: T1-weighted isotropic brain scans were collected at 3T from seven European centers in 60 RRMS patients and 65 healthy controls (HCs). Patients underwent clinical and neuropsychological examinations. Cortical thickness (CTh) measures were calculated using FreeSurfer (failing in four) and both lobar and vertex-based general linear model (GLM) analyses were compared between study groups. Results: Twenty (36%) MS patients were classified as CI. Mean global CTh was smaller in RRMS patients compared to HCs (left 2.43 vs. 2.53 mm, right 2.44 vs. 2.54 mm, p < 0.001). Multivariate GLM regional analysis showed significantly more temporal thinning in CI compared to CP patients. Verbal memory scores correlated to regional cortical thinning in the insula whereas visual memory scores correlated to parietal thinning. Conclusions: This multicenter study showed mild global cortical thinning in RRMS. The extent of thinning is less pronounced than previously reported. Only subtle regional differences between CI and CP patients were observed, some of which related to specific cognitive domains. [ABSTRACT FROM AUTHOR]

Background: Cognitive deficits are frequent in multiple sclerosis (MS) and have been associated with morphologic brain changes. Less information exists on their extent and relation to MRI findings in clinically isolated syndrome (CIS). It is also unclear if structural changes as detected by magnetization transfer (MT) imaging may provide an additional explanation for cognitive dysfunction.Objective: To analyse the extent of cognitive deficits and their relation to MRI metrics including MT imaging in CIS compared to relapsing-remitting MS (RRMS).Methods: Forty-four CIS and 80 RRMS patients underwent the Brief Repeatable Battery of Neuropsychological Tests (BRB-N) and a 3 T MRI scan.Results: BRB-N subtests revealed similar results in CIS and RRMS. Impaired mental processing speed was most prevalent in both groups (CIS 13.6%; RRMS 16.3%) and thus served for correlation with MRI metrics. Using stepwise linear regression analyses, the strongest predictor for decreased mental processing speed was normalized cortex volume (p < 0.001) followed by T2-lesion load (p < 0.05) in RRMS, whereas cortical MT ratio was the only MRI parameter associated with decreased mental processing speed in CIS (p < 0.005).Conclusion: Cognitive dysfunction occurs in CIS in a pattern similar to RRMS, with impaired mental processing speed being most prevalent. Cortical MT-ratio changes may be an early sign for tissue changes related to impaired mental processing speed in CIS while this association shifts to increased signs of cortical atrophy and lesion load in RRMS. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is a disabling disease of the central nervous system. People living with MS often have co-existing sleep disorders and cognitive dysfunction. The objective of this study was to scrutinize the relationship between cognitive outcomes and sleep conditions in MS. Methods: This study followed the Joanna Briggs Institute's (JBI) and PRISMA guidelines. PubMed, Scopus, Embase, and Web of Science databases were searched and original studies delineating the relationship between sleep status and cognitive findings in MS patients‌ were included. The risk of bias was assessed using the JBI critical appraisal tools. Results: In the final review, out of 1635 screened records, 35 studies with 5321 participants were included. Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and polysomnography were the most common assessment tools for evaluation of sleep condition, and cognitive evaluations were conducted using the tests including Paced Auditory Serial Addition Test (PASAT), California Verbal Learning Test (CVLT), Symbol Digit Modalities Test (SDMT) and Brief Visuospatial Memory Test (BVMT). Assessing the quality of studies showed no significant bias in most of the included articles. A link between sleep condition and cognitive abilities was suggested in the literature, especially with objective measurement of sleep condition; however, current evidence did not support a substantial association between self-reported sleep quality and processing speed and working memory in patients with MS. Discussion: Evidence proposes sleep is an independent factor associated with cognitive outcomes in MS. Given the limitations of the evidence such as the lack of well-designed prospective studies, these findings need to be interpreted with caution. [ABSTRACT FROM AUTHOR]

Myasthenia gravis (MG) is a neuromuscular disease of autoimmune etiology and chronic evolution. In addition to the muscle weakness and fatigue that characterize MG, in some studies patients show an inferior performance in cognitive tasks and difficulties in recognizing basic emotions from facial expressions. However, it remains unclear if these difficulties are due to anxious–depressive symptoms that these patients present or related to cognitive abilities, such as facial recognition. This study had a descriptive cross-sectional design with a sample of 92 participants, 52 patients with MG and 40 healthy controls. The data collection protocol included measures to assess recognition of facial expressions (BRFT), facial emotional expression (FEEL), and levels of anxiety and depression (HADS). The MG group had worse performance than the control group in recognizing "fear" (p = 0.001; r = 0.344), "happiness" (p = 0.000; r = 0.580), "disgust" (p = 0.000; r = 0.399), "surprise" (p = 0.000; r = 0.602), and "anger" (p = 0.007; r = 0.284). Likewise, the MG group also underperformed in facial recognition (p = 0.001; r = 0.338). These difficulties were not related to their levels of anxiety and depression. Alterations were observed both in the recognition of facial emotions and in facial recognition, without being mediated by emotional variables. These difficulties can influence the interpersonal interaction of patients with MG. [ABSTRACT FROM AUTHOR]

Background: Brain derived neurotrophic factor (BDNF) played a role in neuroplasticity and was involved in several autoimmune diseases including multiple sclerosis (MS). Val66Met polymorphism affects BDNF secretion and needs more research to determine its impact. This study aimed to evaluate the role of this polymorphism on motor disability and cognition in MS patients. Methods: This is a case control study involving 100 subjects (50 MS patients, 50 controls). A genetic testing for BDNF Val66Met and a thorough neuropsychological evaluation using the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) in the approved Arabic version were performed for all subjects. Progressive clinical disability measurements by the Expanded Disability Status Scale (EDSS) along with the Multiple Sclerosis Severity Scale (MSSS) were done for MS patients. Results: MS patients with the Met allele variant had longer course duration (P=0.009). Val/Val genotype patients had significantly more frequent relapses (P=0.017). Met carrier patients showed lower scores on all subtests of BICAMS but only reached a statistically significant difference in the Symbol digit modality test (SDMT) (P=0.04). In the logistic regression analysis for factors predicting disability, BDNF Val66Met polymorphism was not associated with disease disability. More frequent relapses, presence of high lesion load and cervical lesions on MRI brain could predict increasing disability on multivariate analysis. Conclusions: MS patients having met allele of the BDNF gene had significant cognitive dysfunction on the SDMT. However, our results could not suggest a significant effect of this polymorphism on other subtests of BICAMS or on clinical disability. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system characterized by a broad and unpredictable range of symptoms, including cognitive and sociocognitive dysfunction. Among these social-cognitive functions, moral judgment has been explored in persons with MS (PwMS) using moral dilemmas, where participants must decide whether to sacrifice one person to save a greater number. Opting for such a sacrifice reflects utilitarian reasoning (sacrificing one for the benefit of many is deemed acceptable), while refusing reflects deontological reasoning (such sacrifice is considered morally wrong). Compared to controls, PwMS have been shown to make greater deontological moral choices in such dilemmas. Objectives: While PwMS have demonstrated a higher tendency for deontological moral choices in moral dilemmas compared to controls, the underlying determinants of this reasoning pattern remain unclear. In this project, we aim to investigate cognitive, emotional, and motivational factors that may explain deontological decision-making in MS. Methods and analysis: We will recruit a sample of 45 PwMS and 45 controls aged 18-55 years. The type of response, deontological or utilitarian, to a series of 20 vignettes of moral dilemmas will constitute the primary outcomes. Global cognitive performance, positivity bias, alexithymia and empathy levels as well as emotional reactivity measured by electrodermal activity (EDA) during moral dilemmas will be secondary outcomes. Ethics and dissemination: Ethics approval was granted by a national ethical committee (CPP Ouest III, national number 2023-A00447-38). The project is sponsored by the ARSEP Foundation. Findings will be presented at national and international conferences, as well as published in peer-reviewed scientific journals. [ABSTRACT FROM AUTHOR]

Objective: White matter hyperintensity (WMH) in patients with cerebral small vessel disease (CSVD) is strongly associated with cognitive impairment. However, the severity of WMH does not coincide fully with cognitive impairment. This study aims to explore the differences in the dynamic functional network connectivity (dFNC) of WMH with cognitively matched and mismatched patients, to better understand the underlying mechanisms from a quantitative perspective. Methods: The resting-state functional magnetic resonance imaging (rsfMRI) and cognitive function scale assessment of the patients were acquired. Preprocessing of the rs-fMRI data was performed, and this was followed by dFNC analysis to obtain the dFNC metrics. Compared the dFNC and dFNC metrics within different states between mismatch and match group, we analyzed the correlation between dFNC metrics and cognitive function. Finally, to analyze the reasons for the differences between the mismatch and match groups, the CSVD imaging features of each patient were quantified with the assistance of the uAI Discover system. Results: The 149 CSVD patients included 20 cases of "Type I mismatch," 51 cases of Type I match, 38 cases of "Type II mismatch," and 40 cases of "Type II match." Using dFNC analysis, we found that the fraction time (FT) and mean dwell time (MDT) of State 2 differed significantly between "Type I match" and "Type I mismatch"; the FT of States 1 and 4 differed significantly between "Type II match" and "Type II mismatch." Correlation analysis revealed that dFNC metrics in CSVD patients correlated with executive function and information processing speed among the various cognitive functions. Through quantitative analysis, we found that the number of perivascular spaces and bilateral medial temporal lobe atrophy (MTA) scores differed significantly between "Type I match" and "Type I mismatch," while the left MTA score differed between "Type II match" and "Type II mismatch." Conclusion: Different mechanisms were implicated in these two types of mismatch: Type I affected higher-order networks, and may be related to the number of perivascular spaces and brain atrophy, whereas Type II affected the primary networks, and may be related to brain atrophy and the years of education. [ABSTRACT FROM AUTHOR]

Cognitive Reserve (CR) reflects acquired knowledge, skills, and abilities throughout life, and it is known for modulating cognitive efficiency in healthy and clinical populations. CR, which was initially proposed to explain individual differences in the clinical presentation of dementia, has subsequently been extended to healthy ageing, showing its role in cognitive efficiency also during middle age. Recently, CR has been linked to affective processes in psychiatric conditions such as schizophrenia, major depressive and anxiety symptoms, and psychological distress, suggesting its potential role in emotional expression and regulation. Whether the role of CR in mental health extends to non-pathological adults, and whether this is only relevant in older age is not yet clear. The aim of this work was therefore to explore the relationship between CR and mental health in healthy adults, with a focus on middle adulthood (40–60). In a sample of 96 participants, we found a positive association between CR and mental health outcomes, such that a higher cognitive reserve index corresponded to fewer mental health reported symptoms. Specifically, a higher CR reflecting professional activities was associated with lower stress levels, especially in middle agers. Taken together, these data therefore suggest that engaging occupations may help maintain a robust mental health, especially by reducing stress symptoms during middle age. These results broaden previous findings suggesting that CR relates to affective components of mental health in middle aged and older adults. [ABSTRACT FROM AUTHOR]

The Hispanic/Latino population is one of the largest and most diverse ethnoracial groups in the United States at high risk for dementia. We examined cognitive constructs and associations with subsequent hippocampal volume (HV) and white matter hyperintensity volume (WMHV). Participants were from the Hispanic Community Health Study/Study of Latinos–Magnetic Resonance Imaging Study (n = 2029). We examined confirmatory factor analysis and longitudinal invariance using neurocognitive scores at Visits 1 (2008–2011) and 2 (2014–2018) and path analyses. We obtained a longitudinally invariant two‐factor episodic memory (EM) and working memory (WM) construct. Lower EM profile at both visits was associated with greater WMHV and smaller HV at Visit 2. Lower WM profile at both visits was associated with larger WMHV and smaller HV at Visit 2. Neurocognitive profiles were associated with subsequent neurodegeneration in a sample of Hispanics/Latinos. Identifying neurocognitive risk profiles may lead to early detection and intervention, and significantly impact the course of neurodegeneration. Highlights: Cognitive profiles predict brain integrity up to 10 years later.We observed two‐factor latent memory constructs and longitudinal invariance.These findings were observed in a Hispanic/Latino cohort. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is an age-related neurodegenerative disease characterized by memory loss and cognitive decline. Despite significant efforts over several decades, our understanding of the pathophysiology of this disease is still incomplete. Myelin is a multi-layered membrane structure ensheathing neuronal axons, which is essential for the fast and effective propagation of action potentials along the axons. Recent studies highlight the critical involvement of myelin in memory consolidation and reveal its vulnerability in various pathological conditions. Notably, apart from the classic amyloid hypothesis, myelin degeneration has been proposed as another critical pathophysiological feature of AD, which could occur prior to the development of amyloid pathology. Here, we review recent works supporting the critical role of myelin in cognition and myelin pathology during AD progression, with a focus on the mechanisms underlying myelin degeneration in AD. We also discuss the complex intersections between myelin pathology and typical AD pathophysiology, as well as the therapeutic potential of pro-myelinating approaches for this disease. Overall, these findings implicate myelin degeneration as a critical contributor to AD-related cognitive deficits and support targeting myelin repair as a promising therapeutic strategy for AD. [ABSTRACT FROM AUTHOR]

Cerebral small vessel disease (SVD) can disrupt the global brain network and lead to cognitive impairment. Conversely, cognitive reserve (CR) can improve one's cognitive ability to handle damaging effects like SVD, partly by optimizing the brain network's organization. Understanding how SVD and CR collectively influence brain networks could be instrumental in preventing cognitive impairment. Recently, brain redundancy has emerged as a critical network protective metric, providing a nuanced perspective of changes in network organization. However, it remains unclear how SVD and CR affect global redundancy and subsequently cognitive function. Here, we included 121 community‐dwelling participants who underwent neuropsychological assessments and a multimodal MRI examination. We visually examined common SVD imaging markers and assessed lifespan CR using the Cognitive Reserve Index Questionnaire. We quantified the global redundancy index (RI) based on the dynamic functional connectome. We then conducted multiple linear regressions to explore the specific cognitive domains related to RI and the associations of RI with SVD and CR. We also conducted mediation analyses to explore whether RI mediated the relationships between SVD, CR, and cognition. We found negative correlations of RI with the presence of microbleeds (MBs) and the SVD total score, and a positive correlation of RI with leisure activity‐related CR (CRI‐leisure). RI was positively correlated with memory and fully mediated the relationships between the MBs, CRI‐leisure, and memory. Our study highlights the potential benefits of promoting leisure activities and keeping brain redundancy for memory preservation in older adults, especially those with SVD. [ABSTRACT FROM AUTHOR]

Background: Up to 65% of people with multiple sclerosis (PwMS) develop cognitive deficits, which hampers their ability to work, participating in day-to-day life and ultimately reducing quality of life (QoL). Early cognitive symptoms are often less tangible to PwMS and their direct environment and are noticed only when symptoms and work functioning problems become more advanced, i.e., when (brain) damage is already advanced. Treatment of symptoms at a late stage can lead to cognitive impairment and unemployment, highlighting the need for preventative interventions in PwMS. Aims: This study aims to evaluate the (cost-) effectiveness of two innovative preventative interventions, aimed at postponing cognitive decline and work functioning problems, compared to enhanced usual care in improving health-related QoL (HRQoL). Methods: Randomised controlled trial including 270 PwMS with mild cognitive impairment, who have paid employment ≥ 12 h per week and are able to participate in physical exercise (Expanded Disability Status Scale < 6.0). Participants are randomised across three study arms: 1) 'strengthening the brain' – a lifestyle intervention combining personal fitness, mental coaching, dietary advice, and cognitive training; 2) 'strengthening the mind' – a work-focused intervention combining the capability approach and the participatory approach in one-on-one coaching by trained work coaches who have MS themselves; 3) Control group—receiving general information about cognitive impairment in MS and receiving care as usual. Intervention duration is four months, with short-term and long-term follow-up measurements at 10 and 16 months, respectively. The primary outcome measure of the Don't be late! intervention study will be HRQoL as measured with the 36-item Short Form. Secondary outcomes include cognition, work related outcomes, physical functioning, structural and functional brain changes, psychological functioning, and societal costs. Semi-structured interviews and focus groups with stakeholders will be organised to qualitatively reflect on the process and outcome of the interventions. Discussion: This study seeks to prevent (further) cognitive decline and job loss due to MS by introducing tailor-made interventions at an early stage of cognitive symptoms, thereby maintaining or improving HRQoL. Qualitative analyses will be performed to allow successful implementation into clinical practice. Trial registration: Retrospectively registered at ClinicalTrials.gov with reference number NCT06068582 on 10 October 2023. [ABSTRACT FROM AUTHOR]

Aim: To describe current scientific knowledge on cognitive impairment and emotional disturbances (anxiety and depression) in younger adult patients after ischemic stroke. Design: A scoping review. Methods: For the search, the following scientific databases were utilized: Web of Science, MEDLINE (Ovid), ScienceDirect (Elsevier), PsycInfo (EBSCO), Scopus (Elsevier), and ProQuest. Relevant studies were identified by searching publications from 2000 to July 2023. Results: A total of eight studies were ultimately included in the review. Cognitive impairment occurred in a range between 39.4% and 40%. This encompassed various aspects of cognitive function, such as working memory, processing speed, global cognitive function, immediate and delayed memory, attention, and executive functioning. Depression had an incidence rate ranging from 10.8% to 16.8%. Several risk factors were associated with a higher likelihood of developing generalized anxiety. These included younger age, more depressive symptoms, lower education, unemployment, a history of depression, and alcohol use. In the context of depressive symptoms, a higher risk was linked to lower education and unemployment. Conclusion: The included studies highlighted the need to assess these issues not only at the time of patient discharge but, more importantly, during the stage of further recovery. This can contribute to the creation of tailored interventions for these individuals. [ABSTRACT FROM AUTHOR]

Recent advances in blood-based biomarkers of Alzheimer's Disease (AD) show great promise for clinical applications, offering a less invasive alternative to current cerebrospinal fluid (CSF) measures. However, the relationships between these biomarkers and specific cognitive functions, as well as their utility in predicting longitudinal cognitive decline, are not yet fully understood. This descriptive review surveys the literature from 2018 to 2023, focusing on the associations of amyloid-β (Aβ), Total Tau (t-Tau), Phosphorylated Tau (p-Tau), Neurofilament Light (NfL), and Glial Fibrillary Acidic Protein (GFAP) with cognitive measures. The reviewed studies are heterogeneous, varying in design and population (cognitively unimpaired, cognitively impaired, or mixed populations), and show results that are sometimes conflicting. Generally, cognition positively correlates with Aβ levels, especially when evaluated through the Aβ42/Aβ40 ratio. In contrast, t-Tau, p-Tau, Nfl, and GFAP levels typically show a negative correlation with cognitive performance. While p-Tau measures generally exhibit stronger associations with cognitive functions compared to other biomarkers, no single blood marker has emerged as being predominantly linked to a specific cognitive domain. These findings contribute to our understanding of the complex relationship between blood biomarkers and cognitive performance and underscore their potential utility in clinical assessments of cognition. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment (CI) is a common and disabling symptom during the disease even in the earliest "preclinical" phase of patients with MS (pwMS). This study aims to assess cognitive function by measuring P300 event-related potential (ERP) and to look into the relationship between P300 abnormalities with the severity of the physical disability, education level, and disease duration. Methods: Fifty pwMS (28 females and 22 males) aged 20–54 years and fifty healthy subjects comprised of 21 females and 29 males aged 18–50 years serves as the control group was studied. All participants underwent medical history, neurological examination, cognitive functions using the Montreal Cognitive Assessment scale (MoCA) and the P300 ERP. Results: In this study, 48% of pwMS had CI. They had a longer P300 latency and a lower amplitude. Those with impaired cognition had a longer duration of illness and higher Expanded Disability Status Scale (EDSS), whereas those with intact cognition had a higher education level. P300 latency was correlated positively with EDSS and disease duration, but negatively with education level. P300 amplitude was found to be negatively correlated with EDSS, and disease duration but positively to the education level. Conclusions: P300, as a non-invasive test, would support the presence of CI in pwMS patients and could be used for screening in daily practice. P300 has a strong relationship with illness duration, disease subtypes, EDSS, and education level. [ABSTRACT FROM AUTHOR]

Background: The Symbol Digit Modalities Test (SDMT) is a gold-standard measure of cognitive efficiency and processing speed for people with multiple sclerosis (PwMS) but relies on vision and oculomotor function. Objectives: To develop and validate a new processing speed test with minimal memory involvement and no eye function requirements. Methods: We created an Auditory Test of Processing Speed (ATOPS). A total of 122 PwMS, of whom 33 were severely disabled (median Expanded Disability Status Scale 8.0) and 37 healthy volunteers (HVs), were enrolled. We assessed sensitivity to discriminate MS participants from HVs, convergent validity between ATOPS and SDMT, sensitivity to discriminate between cognitively impaired (CI) and cognitively preserved (CP) MS participants, and correlations with MS pathology (overall brain lesion burden). Acceptability was examined with completion rates and participant ratings of ATOPS. Results: ATOPS discriminated PwMS from HVs (d = 0.739–0.856), correlated with SDMT (| r | = 0.528–0.587), discriminated between CI and CP PwMS (d = 0.623–0.776), and correlated with lesion burden (r = 0.332–0.436). All groups indicated high favorability of ATOPS and severely disabled MS patients could be assessed by ATOPS more frequently than by SDMT (100% vs. 72.4% completion). Conclusions: ATOPS is a novel, accessible, and acceptable cognitive processing speed test that may be useful in clinical and/or research settings. [ABSTRACT FROM AUTHOR]

Background: Depression symptoms are prevalent in multiple sclerosis (MS) and associated with poorer cognition in cross-sectional studies; it is unknown whether changes in depression symptoms track with cognitive changes longitudinally. Objective: Investigate whether changes in depression symptoms correspond with cognitive changes over time in MS, and identify specific cognitive functions related to depression symptoms. Method: Persons with early relapse-onset MS (n = 165) completed a depression questionnaire (Beck Depression Inventory FastScreen) and tests of cognitive speed, executive control, and memory at baseline and 3-year follow-up. One-way ANOVAs assessed differences in cognitive change across participants with worsened, stable, or improved depression symptoms from baseline to year 3. Results: Change in depression symptoms was related to change in executive control (p = 0.001, ηp2 = 0.08; worsened mood with worsened executive control; improved mood with improved executive control), even when adjusting for cognitive speed (p = 0.002, ηp2 = 0.08). There were no links to cognitive speed (p = 0.826) or memory (p = 0.243). Regarding individual depression symptoms, executive control was related to loss of pleasure and suicidal thoughts. Conclusions: Executive control tracks with depression symptoms, raising hope that management of mood may improve executive control. The specific link between executive control and anhedonia implicates dysfunctional reward processing as a key component of MS depression. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis is a chronic neuro-inflammatory disease of the brain and central nervous system. We aimed at assessing the cognitive functions present in adult patients with multiple sclerosis in remission phase of the disease comparing them to healthy control group. Results: This is a cross sectional study using Penn Computerized Neurocognitive Battery (CNB) to measure performance accuracy and speed on specific neurobehavioral domains comparing MS group to healthy group. The MS group showed lower statistically significant difference in the accuracy of spatial memory, the motor speed, Non-verbal reasoning, Spatial orientation, social cognition, and working memory. Also, MS group showed statistically significant longer reaction time in facial memory, attention, spatial orientation, and non-verbal reasoning. Conclusions: Attention, spatial orientation, non- verbal reasoning, Facial memory, working memory, social cognition and spatial memory were affected in patients with MS during their remission phase. cognitive evaluation should constitute a major part of the clinical examination in MS, especially when impairment seems likely. [ABSTRACT FROM AUTHOR]

The concept of Cognitive Reserve (CR) refers to the individual differences allowing some people to cope better with brain pathology. The aim of the present review was to explore the relationship between CR and cognition in adulthood. This association has been addressed in several neuro(psycho)logical disorders and in healthy elderly people. However, few studies explored this issue in adulthood (age range 18–65), when individuals might take advantage the most from psychoeducational approaches aimed at increasing CR. For our systematic review, we selected studies assessing CR and adopting neuropsychological and experimental tasks for evaluation of cognitive functioning in healthy individuals. In the selected articles, we examined the relationship of singular proxies, composite indexes or standardized scales of CR with measures of general cognition, attention, inhibitory control, verbal fluency, constructional abilities, and verbal and spatial memory. The results suggested a positive relationship between singular CR proxies, composite indexes or standardized scales, and almost all the explored cognitive domains. No clear conclusion could be made on constructional abilities due to the scarcity of available studies. CR seems associated with better cognitive performance in adulthood, but definite methodological improvements and the use of standardized scales for CR are necessary to reduce inconsistencies among studies. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment (CI) is a prevalent and debilitating manifestation of multiple sclerosis (MS); however, it is not included in the widely used concept of No Evidence of Disease Activity (NEDA-3). We expanded the NEDA-3 concept to NEDA-3 + by encompassing CI assessed through the Symbol Digit Modality Test (SDMT) and evaluated the effect of teriflunomide on NEDA3 + in patients treated in a real-world setting. The value of NEDA-3 + in predicting disability progression was also assessed. Methods: This 96-weeks observational study enrolled patients already on treatment with teriflunomide for ≥ 24 weeks. The predictiveness of NEDA-3 and NEDA-3 + at 48 weeks on the change in motor disability at 96 weeks was compared through a two-sided McNemar test. Results: The full analysis set (n = 128; 38% treatment naïve) featured relatively low level of disability (baseline EDSS = 1.97 ± 1.33). NEDA-3 and NEDA-3 + statuses were achieved by 82.8% and 64.8% of patients, respectively at 48 weeks vs. baseline, and by 57.0% and 49.2% of patients, respectively at 96 weeks vs. baseline. All patients except one were free of disability progression at Week 96, and NEDA-3 and NEDA-3 + were equally predictive. Most patients were free of relapse (87.5%), disability progression (94.5%) and new MRI activity (67.2%) comparing 96 weeks with baseline. SDMT scores were stable in patients with baseline score ˃35 and improved significantly in those with baseline score ≤ 35. Treatment persistence was high (81.0% at Week 96). Conclusion: Teriflunomide confirmed its real-world efficacy and was found to have a potentially beneficial effect on cognition. [ABSTRACT FROM AUTHOR]

Background: Information about cognitive functioning is vital in the management of stroke, but the literature is mostly based on data from individuals older than 50 years of age who make up the majority of the stroke population. As cognitive functioning is subject to change due to aging, it is unclear whether such cognitive impairment patterns from the general stroke literature apply to the growing population of younger people with a stroke. Aim: The aim of the study was to conduct a systematic review and meta-analysis of the proportion and severity of cognitive impairment in young-stroke patients. Summary of review: MEDLINE, Embase, PsycINFO, and Web of Science were systematically searched up to 11 October 2022. Studies were included if they reported on a population of young-stroke patients, evaluated cognitive functioning as an outcome measure, and reported original data. We estimated the pooled prevalence rates for cognitive impairment and for aphasia. In addition, we calculated the pooled estimates for the severity of impairment per cognitive domain in the chronic phase (defined as >6 months post-stroke). Six hundred thirty-five articles were identified, of which 29 were eligible for inclusion. The pooled prevalence of cognitive impairment was 44% (k = 10; 95% confidence interval (CI): 34–54%) and of aphasia 22% (k = 13; 95% CI: 12–39%). Young-stroke patients in the chronic phase performed worse than stroke-free healthy age-appropriate controls across all cognitive domains examined, with Hedges' g effect sizes ranging from −0.49 to −1.64. Conclusion: Around half of all young-stroke patients present with cognitive impairment and around a quarter with aphasia. Our data suggest that patterns of impairment in young-stroke patients follow those in the general stroke literature. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic, neurodegenerative, inflammatory condition usually associated with physical disability. Clinical care has been skewed toward the physical manifestations of the disease, yet a range of silent symptoms occurs including the cognitive aspects of MS. In a 2018 meeting of MS in the 21st Century (MS21), an international steering committee comprising both specialists and patient experts recognised that the 'invisible symptoms' of MS pose a significant challenge to patient engagement. These findings prompted the European Charcot Foundation (ECF) MS21 symposium (2020), where a panel consisting of two leading MS clinicians and an MS patient expert (who were all members of the MS21 steering group) gathered to discuss the impact of cognitive impairment on the everyday lives of people with MS. The perspectives and experiences of the panellists are summarised in this paper. The key points raised were that (1) the cognitive manifestations of MS are under-recognised and have consequently been undermanaged from a clinical perspective and (2) cognitive impairment due to MS has a significant impact upon daily living and patient quality of life. During discussions about how these challenges can be addressed, the panel advocated for an improvement in education about cognitive symptoms for people living with MS and healthcare professionals (HCPs) to raise awareness about this aspect of MS. Furthermore, the panel emphasised the importance of open and proactive communication between HCPs and their patients with MS about cognitive symptoms to reduce the stigma attached to these symptoms. In the opinion of the panel, future clinical trials which include cognitive outcomes as key endpoints are needed. Reflecting this point, cognitive impairment in MS care also needs to be treated as an important disease symptom, as is done with physical symptoms of the disease. Implementing early and routine cognition screening and promoting measures for protecting cognition to people living with MS, such as cognitive rehabilitation and a 'brain-healthy' lifestyle, are actions which can drive forward the recognition of cognitive impairment as a care priority. If prioritised as highly as physical disability in both the MS care and clinical drug development setting, and proactively discussed in conversations between HCPs and patients with MS, the 'invisibility' of cognitive impairment in MS can be lifted and a better quality of life can be promoted for people living with MS. Plain Language Summary: Multiple sclerosis is a long-term condition which affects the brain and nervous system. Multiple sclerosis care has often focused more on the physical aspects of the disease than its mental challenges. Examples of mental challenges are brain fog, which can make it hard to organise thoughts, and memory problems. In 2020, the Multiple Sclerosis in the 21st Century group held a meeting at a medical conference called the European Charcot Foundation. In this conference, a patient expert living with multiple sclerosis, together with a neuropsychologist and neurologist both specialising in multiple sclerosis, discussed its mental symptoms and why they are not always recognised and addressed by people with multiple sclerosis and their healthcare teams. The group emphasised that these symptoms can considerably affect the day-to-day lives of people who experience them, stressing that this is a key reason why mental symptoms need to be better prioritised in care. The group advocated for early and frequent cognition testing to be a part of the standard care approach, as is the case with physical symptoms. They also urged healthcare professionals to promote a 'brain-healthy' lifestyle to their patients with multiple sclerosis and to encourage participation in cognitive rehabilitation programmes to maintain their mental abilities in the long run. Finally, the group discussed that more drug development studies that specifically assess how a treatment can reduce mental symptoms are needed: in this way, research and healthcare approaches can better prioritise mental symptoms. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment is present in 40-65% of patients with multiple sclerosis (pwMS). Objectively measured cognitive performance often does not match patients' subjective perception of their own performance. Objective: We aimed to compare cognitive performance and subjective perception of cognitive deficits between pwMS and healthy controls (HCs), as well as the accuracy of subjective perception. Methods: In total, 54 HC and 112 pwMS (relapsing-remitting, RRMS, and progressive PMS) underwent neuropsychological evaluation and completed perceived deficit, fatigue, and anxiety-depression scales. Participants were classified according to their consistency between subjective self-evaluation of cognitive abilities and objective cognitive performance to assess accuracy. Regression models were used to compare cognitive performance between groups and explore factors explaining inaccuracy in the estimation of cognitive performance. Results: PMS showed greater and more widespread cognitive differences with HC than RRMS. No differences were found between pwMS and HC in the perception of deficit. PMS had higher ratios of overestimators. In explaining inaccuracy, fatigue and cognitive preservation were found to be risk factors for underestimation, whereas physical disability and cognitive impairment were risk factors for overestimation. Conclusion: PwMS have metacognitive knowledge impairments. This study provides new information about metacognition, data on the prevalence of impairments over a relatively large sample of PwMS, and new insights into factors explaining it. Anosognosia, related to cognitive impairment, may be present in pwMS. Fatigue is a key factor in underestimating cognition. [ABSTRACT FROM AUTHOR]

Cognitive-linguistic deficits are a concern in multiple sclerosis (MS). Thus, clinical management requires knowledge of how impaired cognition associated with MS impacts language performance during everyday communication tasks. This study investigated language performance in narrative monologues produced by individuals with MS compared to healthy controls and the correlations between language performance and cognitive function for the individuals with MS. Thirteen individuals with MS and 13 controls were studied. Four neuropsychological tests from the Minimal Assessment of Cognitive Function in MS confirmed that individuals with MS had impaired cognition and an auditory-perceptual evaluation confirmed that they did not have dysarthria. Narratives were analyzed using the Systematic Analysis of Language Transcripts (SALT). Primary linguistic variables included inter-sentence cohesion adequacy, subordination index, moving average type-token ratio (MATTR), and mean length of utterances (MLU). Secondary linguistic measures included the total number of words, mazes, utterances, and abandoned utterances. Measures of disease severity, depression, and fatigue were also obtained. When controlling for age and fatigue, the total number of words was the only linguistic measure that significantly differed between groups. Participants with MS produced more words than controls. Significant correlations indicated strong associations between MATTR, MLU, abandoned utterances, and subordination index and the cognitive domains of processing speed and/or executive function. Results suggest that communicative competence during everyday speaking tasks may be undermined by off-topic verbose speech, reduced detail, and unfinished thoughts for individuals with MS with impaired processing speed and/or executive function. [ABSTRACT FROM AUTHOR]

Objective: We aimed at examining the effects of a known metacognitive training in MS (MaTiMS) and its modification with an additional neuroeducational module and mindfulness-based exercises (MaTiMS-modified) on neuropsychiatric and cognitive outcomes in people with progressive multiple sclerosis (pwpMS). Exploratively, we investigated whether the modification may show an additional benefit. Methods: Both interventions were administered in small groups of ambulatory patients. Neuropsychological testing before and after the 3- to 4-week intervention phase comprised patient reported outcomes and cognitive tests. After 3, 6 and 12 months, participants completed online surveys. Analysis of change scores (between baseline and retest) with t-tests (Mann–Whitney U and Wilcoxon tests, respectively) and mixed ANCOVAs with repeated measures for comparison of both interventions were conducted. Results: A total of 65 pwpMS turned to a final sample of 50 (n = 15 excluded due to drop-outs, occurrence of relapse or steroid treatment). Change scores within MaTiMS revealed no significant effect on the PDQ-20 total score and only a significant effect on the subscale retrospective memory lasting 3 months with a moderate effect size. In contrast, MaTiMS-modified revealed a highly significant change in PDQ-20 total compared to baseline and significant improvements with small to moderate effect sizes on all PDQ-20 subscales (lasting until 3 months), in self-efficacy, stress, visuo-spatial working memory (moderate effect sizes), and fatigue (small effect size). While no interaction effect between time and group could be revealed, a significant main effect for time was found in PDQ-20 total. Conclusion: Both MaTiMS and MaTiMS-modified positively affected perceived cognitive deficits. However, our data speak in favor of additional benefits by adding neuroeducational and mindfulness-based exercises thus being valuable methods to support brain health including self-efficacy, perceived stress, and fatigue, even in patients with a chronic and progressive brain disease. [ABSTRACT FROM AUTHOR]

Our research studied relapsing-remitting multiple sclerosis (RRMS). In half of the RRMS cases, mild cognitive difficulties are present, but often remain undetected despite their adverse effects on individuals' daily life. Detecting subtle cognitive alterations using speech analysis have rarely been implemented in MS research. We applied automatic speech recognition technology to devise a speech task with potential diagnostic value. Therefore, we used two narrative tasks adjusted for the neural and cognitive characteristics of RRMS; namely narrative recall and personal narrative. In addition to speech analysis, we examined the information processing speed, working memory, verbal fluency, and naming skills. Twenty-one participants with RRMS and 21 gender-, age-, and education-matched healthy controls took part in the study. All the participants with RRMS achieved a normal performance on Addenbrooke's Cognitive Examination. The following parameters of speech were measured: articulation and speech rate, the proportion, duration, frequency, and average length of silent and filled pauses. We found significant differences in the temporal parameters between groups and speech tasks. ROC analysis produced high classification accuracy for the narrative recall task (0.877 and 0.866), but low accuracy for the personal narrative task (0.617 and 0.592). The information processing speed affected the speech of the RRMS group but not that of the control group. The higher cognitive load of the narrative recall task may be the cause of significant changes in the speech of the RRMS group relative to the controls. Results suggest that narrative recall task may be effective for detecting subtle cognitive changes in RRMS. [ABSTRACT FROM AUTHOR]

Early investigations linking language and genetics were focused on the evolution of human communication in populations with developmental speech and language disorders. Recently, studies suggest that genes may also modulate recovery from post-stroke aphasia. Our goal is to review current literature related to the influence of genetics on post-stroke recovery, and the implications for aphasia rehabilitation. We describe candidate genes implicated by empirical findings and address additional clinical considerations. We describe existing evidence and mechanisms supporting future investigations into how genetic factors may modulate aphasia recovery and propose that two candidate genes, brain derived neurotrophic factor (BDNF) and apolipoprotein E (APOE), may be important considerations for future research assessing response to aphasia treatment. Evidence suggests that BDNF is important for learning, memory, and neuroplasticity. APOE influences cognitive functioning and memory in older individuals and has also been implicated in neural repair. Moreover, recent data suggest an interaction between specific alleles of the BDNF and APOE genes in influencing episodic memory. Genetic influences on recovery from aphasia have been largely unexplored in the literature despite evidence that genetic factors influence behaviour and recovery from brain injury. As researchers continue to explore prognostic factors that may influence response to aphasia treatment, it is time for genetic factors to be considered as a source of variability. As the field moves in the direction of personalized medicine, eventually allied health professionals may utilize genetic profiles to inform treatment decisions and education for patients and care partners. [ABSTRACT FROM AUTHOR]

Quantifying a significant cognitive change on a neuropsychological battery is essential to assess patients' decline or recovery and offer appropriate care. The reliability of change indices is particularly important in multiple sclerosis (MS), as the course of cognitive impairment is quite unpredictable, due at least in part to substantial interindividual variability. The main objective of this study was to compare six different methods for assessing cognitive change in an MS sample: the SD method, two reliable change indices, two standardized regression-based methods (SRB), and the generalized regression-based method (GSRB). One hundred and twenty-three patients with clinically definite MS and 89 healthy controls underwent a battery of standardized neuropsychological tests assessing cognitive functions that are frequently affected in this disease (i.e., verbal episodic memory, working memory, processing speed and verbal fluency). We observed fairly similar proportions of improvement, decline or stability in the control group whatever the method. By contrast, in the MS sample, regression-based methods with one predictor (i.e., score at T1) and four predictors (i.e., score at T1 and demographic factors: age, sex, education level) detected a significant worsening more often than the reliable change indices while the GSRB method was more consistent with the RCI methods in tasks associated with ceiling effects. The interpretation of a patient's cognitive changes depends on which method is used. The (G)SRB methods appear to be relevant indicators for assessing cognitive change in MS. The addition of demographic factors does not seem to play an important role in the prediction of significant worsening in the MS sample, regardless of cognitive domain. For clinicians, an easy-to-use free shiny app is provided. [ABSTRACT FROM AUTHOR]

Hippocampal blood–brain barrier (BBB) permeability may increase in normal healthy ageing and contribute to neurodegenerative disease. To examine this hypothesis, we investigated the correlation between blood–brain barrier (BBB) permeability, regional brain volume, memory functions and health and lifestyle factors in The Metropolit 1953 Danish Male Birth Cohort. We used dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with a gadolinium-based contrast agent to assess BBB permeability in 77 participants in the cohort. BBB permeability was measured as Ki values in the hippocampus, thalamus and white matter. Over a 10-year period, we observed progressive atrophy of both the left and right hippocampus (p = 0.001). There was no significant correlation between current BBB permeability and hippocampal volume, prior atrophy or cognition. The hippocampus volume ratio was associated with better visual and verbal memory scores (p < 0.01). Regional BBB differences revealed higher Ki values in the hippocampus and white matter than in the thalamus (p < 0.001). Participants diagnosed with type II diabetes had significantly higher BBB permeability in the white matter (p = 0.015) and thalamus (p = 0.016), which was associated with a higher Fazekas score (p = 0.024). We do not find evidence that BBB integrity is correlated with age-related hippocampal atrophy or cognitive functions. The association between diabetes, white matter hyperintensities and increased BBB permeability is consistent with the idea that cerebrovascular disease compromises BBB integrity. Our findings suggest that the hippocampus is particularly prone to age-related atrophy, which may explain some of the cognitive changes that accompany older age, but this prior atrophy is not correlated with current BBB permeability. [ABSTRACT FROM AUTHOR]

Simple Summary: Brain tumours can result in cognitive, language, motor, and visual deficits in paediatric patients by invading the functional regions of the brain and altering neuronal networks. The specific mechanisms of tumour invasion and the cognitive impact of various treatments remain uncertain. In this systematic review, we discuss the functional alteration in the brain of paediatric patients caused by the tumours in different locations. The present study proposes to understand the changes in the functional connectivity of paediatric patients after tumour invasion using resting-state and task-based fMRI. Working memory, language and speech abilities, motor skills, and visual abilities are often impaired in children with brain tumours. This is because tumours can invade the brain's functional areas and cause alterations to the neuronal networks. However, it is unclear what the mechanism of tumour invasion is and how various treatments can cause cognitive impairment. Therefore, this study aims to systematically evaluate the effects of tumour invasion on the cognitive, language, motor, and visual abilities of paediatric patients, as well as discuss the alterations and modifications in neuronal networks and anatomy. The electronic database, PubMed, was used to find relevant studies. The studies were systematically reviewed based on the type and location of brain tumours, cognitive assessment, and pre- and post-operative deficits experienced by patients. Sixteen studies were selected based on the inclusion and exclusion criteria following the guidelines from PRISMA. Most studies agree that tumour invasion in the brain causes cognitive dysfunction and alteration in patients. The effects of a tumour on cognition, language, motor, and visual abilities depend on the type of tumour and its location in the brain. The alteration to the neuronal networks is also dependent on the type and location of the tumour. However, the default mode network (DMN) is the most affected network, regardless of the tumour type and location.Furthermore, our findings suggest that different treatment types can also contribute to patients' cognitive function to improve or deteriorate. Deficits that persisted or were acquired after surgery could result from surgical manipulation or the progression of the tumour's growth. Meanwhile, recovery from the deficits indicated that the brain has the ability to recover and reorganise itself. [ABSTRACT FROM AUTHOR]