The effects of 7-week cognitive training in patients with vascular cognitive impairment,no dementia (the Cog-VACCINE study): A randomized controlled trial

IntroductionEvidence for the efficacy of cognitive training in patients with subcortical vascular cognitive impairment no dementia is still lacking.MethodsA randomized, active controlled design using multidomain, adaptive, computerized cognitive training for 30 minutes, 5 days/week for 7 weeks. Assessments included global cognitive function and executive function (primary outcomes) and brain functional connectivity and structural changes (secondary outcomes).ResultsSixty patients were randomized across three medical centers in Beijing. At the end of the intervention, the cognitive training group showed significant improvement in Montreal Cognitive Assessment relative to the active control group (P = .013) and significantly increased functional connectivity between the left dorsolateral prefrontal cortex and medial prefrontal cortex, which was significantly correlated with Montreal Cognitive Assessment change (P = .017).DiscussionComputerized cognitive training significantly improved global cognitive function, which was supported by the improved brain plasticity. Incorporation of biomarkers should be implemented in cognitive training trials.     

Hippocampal‐parietal dysconnectivity and glutamate abnormalities in unmedicated patients with schizophrenia

Abnormalities in resting state connectivity in schizophrenia (SZ) are now well established, but the biological substrates of these functional alterations remain to be elucidated. We performed a combined functional magnetic resonance imaging and magnetic resonance spectroscopy study in 22 unmedicated patients with SZ and 22 matched healthy controls (HCs) to evaluate resting state functional connectivity of the hippocampus and Glx/Cr (a combined glutamate + glutamine peak normalized to creatine) in the hippocampus and investigate functional and neurometabolic abnormalities and examine the relationship between these. Functional connectivity between the left hippocampus and bilateral precuneus was significantly decreased in unmedicated patients with SZ when compared to HCs [t(4.22), cluster extent (kE) = 751, P_FDRcorr = 0.001, Montreal Neurological Institute coordinates: x = ?4, y = ?56, z = 44]. Glx/Cr in the hippocampus was significantly elevated in SZ (HC: mean = 0.60+/?0.10 SZ: 0.67+/?0.10; F = 5.742; P = 0.02), but was not correlated with functional connectivity deficits (P > 0.05). In this study, we found hippocampal resting state functional connectivity deficits to the precuneus in unmedicated patients with SZ and an increase of Glx/Cr in the hippocampus, but did not observe a direct relationship between these abnormalities. However, our findings do not exclude the possibility of a shared underlying pathology, which warrants further investigation. © 2014 Wiley Periodicals, Inc.     

脑梗死后认知障碍与血清视锥蛋白样蛋白-1水平及神经功能缺损关系的研究

目的探讨脑梗死后认知障碍与血清视锥蛋白样蛋白-1(VILIP-1)水平及神经功能缺损的相关性。方法收集120例急性脑梗死患者,根据蒙特利尔认知评估量表(Mo CA)测评结果分为认知障碍组和认知正常组,比较两组患者入院时和发病1年时血清VILIP-1水平、美国国立卫生研究院卒中量表(NIHSS)评分、Barthel指数(BI)评分,分析Mo CA分值与血清VILIP-1水平、NIHSS评分和BI评分的相关性。结果两组患者发病1年时NIHSS评分均低于入院时(P0.01);BI评分均高于入院时(P0.01)。认知障碍组入院时及发病1年时血清VILIP-1水平高于认知正常组(P0.01);NIHSS评分高于认知正常组(P0.01);BI评分低于认知正常组(P0.01)。入院时及发病1年时所有患者Mo CA分值与血清VILIP-1水平呈负相关(r=-0.736,P=0.000;r=-0.450,P=0.000);与NIHSS评分呈负相关(r=-0.575,P=0.000;r=-0.377,P=0.001);与BI评分呈正相关(r=0.431,P=0.000;r=0.483,P=0.000)。结论脑梗死后认知障碍与血清VILIP-1水平及神经功能的康复有重要相关性。     

Hippocampal‐DMN disconnectivity in MS is related to WM lesions and depression

The hippocampus is part of the default‐mode network (DMN) and is functionally hit early in multiple sclerosis (MS). Hippocampal and DMN dysfunctions have been associated with depression, both in patients with MS and in major depressive disorders. We hypothesized that white matter lesions may contribute, through a disconnection mechanism, to hippocampal dysfunction. To test this, we assessed the relationship between hippocampal resting‐state (RS) functional connectivity (FC) abnormalities with brain T2 lesion volumes and the presence and severity of depression. Structural and RS fMRI images were acquired from 69 patients with cognitively intact MS and 42 matched healthy controls (HC). Depression was quantified using the Montgomery–Asberg Depression Rating Scale. Seed‐voxel hippocampal RS FC was assessed. SPM8 was used for between‐group comparisons and correlation analysis between RS FC abnormalities with clinical and structural MRI variables. Compared to HC, patients with MS showed a significant atrophy of the whole brain and left hippocampus (P < 0.001), and a distributed pattern of decreased RS FC between the hippocampi and several cortical–subcortical regions, which were mostly located within the DMN. Reduced hippocampal RS FC with regions of the DMN was strongly correlated with higher T2 lesion volume, longer disease duration, and the severity of depression and disability. In patients with cognitively preserved MS, brain focal WM lesions are related to the functional integration of the hippocampus to other brain regions of the DMN, suggesting a disconnection syndrome. Such a disruption of hippocampal RS FC is likely to contribute to the occurrence of depression and to clinical disability. Hum Brain Mapp 36:5051–5063, 2015. © 2015 Wiley Periodicals, Inc.     

Functional substrate for memory function differences between patients with left and right mesial temporal lobe epilepsy associated with hippocampal sclerosis

ObjectiveLittle is known about the functional substrate for memory function differences in patients with left or right mesial temporal lobe epilepsy (mTLE) associated with hippocampal sclerosis (HS) from an electrophysiological perspective. To characterize these differences, we hypothesized that hippocampal theta connectivity in the resting-state might be different between patients with left and right mTLE with HS and be correlated with memory performance.MethodsResting-state hippocampal theta connectivity, identified via whole-brain magnetoencephalography, was evaluated. Connectivity and memory function in 41 patients with mTLE with HS (left mTLE = 22; right mTLE = 19) were compared with those in 46 age-matched healthy controls and 28 patients with focal cortical dysplasia (FCD) but without HS.ResultsConnectivity between the right hippocampus and the left middle frontal gyrus was significantly stronger in patients with right mTLE than in patients with left mTLE. Moreover, this connectivity was positively correlated with delayed verbal recall and recognition scores in patients with mTLE. Patients with left mTLE had greater delayed recall impairment than patients with right mTLE and FCD. Similarly, delayed recognition performance was worse in patients with left mTLE than in patients with right mTLE and FCD. No significant differences in memory function between patients with right mTLE and FCD were detected. Patients with right mTLE showed significantly stronger hippocampal theta connectivity between the right hippocampus and left middle frontal gyrus than patients with FCD and left mTLE.ConclusionOur results suggest that right hippocampal–left middle frontal theta connectivity could be a functional substrate that can account for differences in memory function between patients with left and right mTLE. This functional substrate might be related to different compensatory mechanisms against the structural hippocampal lesions in left and right mTLE groups. Given the positive correlation between connectivity and delayed verbal memory function, hemispheric-specific hippocampal–frontal theta connectivity assessment could be useful as an electrophysiological indicator of delayed verbal memory function in patients with mTLE with HS.     

Altered structure and functional connectivity of the hippocampus are associated with social and mathematical difficulties in nonverbal learning disability

The hippocampus is known to play a critical role in a variety of complex abilities, including visual‐spatial reasoning, social functioning, and math. Nonverbal learning disability (NVLD) is a neurodevelopmental disorder characterized by deficits in visual‐spatial reasoning that are accompanied by impairment in social function or mathematics, as well as motor or executive function skills. Despite the overlap between behaviors supported by the hippocampus and impairments in NVLD, the structure and function of the hippocampus in NVLD has not been studied. To address this gap in the literature, we first compared hippocampal volume and resting‐state functional connectivity in children with NVLD (n = 24) and typically developing (TD) children (n = 20). We then explored associations between hippocampal structure, connectivity, and performance on measures of spatial, social, and mathematical ability. Relative to TD children, those with NVLD showed significant reductions in left hippocampal volume and greater hippocampal‐cerebellar connectivity. In children with NVLD, reduced hippocampal volume associated with worse mathematical problem solving. Although children with NVLD exhibited more social problems (social responsiveness scale [SRS]) and higher hippocampal‐cerebellar connectivity relative to TD children, greater connectivity was associated with fewer social problems among children with NVLD but not TD children. Such an effect may suggest a compensatory mechanism. These structural and functional alterations of the hippocampus may disrupt its putative role in organizing conceptual frameworks through cognitive mapping, thus contributing to the cross‐domain difficulties that characterize NVLD.     

A network-based cognitive training induces cognitive improvements and neuroplastic changes in patients with relapsing-remitting multiple sclerosis: an exploratory case-control study

Cognitive impairments are commonly observed in patients with multiple sclerosis and are associated with lower levels of quality of life. No consensus has been reached on how to tackle effectively cognitive decline in this clinical population non-pharmacologically. This exploratory case-control study aims to investigate the effectiveness of a hypothesis-based cognitive training designed to target multiple domains by promoting the synchronous co-activation of different brain areas and thereby improve cognition and induce changes in functional connectivity in patients with relapsing-remitting multiple sclerosis. Forty-five patients(36 females and 9 males, mean age 44.62 ± 8.80 years) with clinically stable relapsing-remitting multiple sclerosis were assigned to either a standard cognitive training or to control groups(sham training and nonactive control). The standard training included twenty sessions of computerized exercises involving various cognitive functions supported by distinct brain networks. The sham training was a modified version of the standard training that comprised the same exercises and number of sessions but with increased processing speed load. The non-active control group received no cognitive training. All patients underwent comprehensive neuropsychological and magnetic resonance imaging assessments at baseline and after 5 weeks. Cognitive and resting-state magnetic resonance imaging data were analyzed using repeated measures models. At reassessment, the standard training group showed significant cognitive improvements compared to both control groups in memory tasks not specifically targeted by the training: the Buschke Selective Reminding Test and the Semantic Fluency test. The standard training group showed reductions in functional connectivity of the salience network, in the anterior cingulate cortex, associated with improvements on the Buschke Selective Reminding Test. No changes were observed in the sham training group. These findings suggest that multi-domain training that stimulates multiple brain areas synchronously may improve cognition in people with relapsing-remitting multiple sclerosis if sufficient time to process training material is allowed. The associated reduction in functional connectivity of the salience network suggests that training-induced neuroplastic functional reorganization may be the mechanism supporting performance gains. This study was approved by the Regional Ethics Committee of Yorkshire and Humber(approval No. 12/YH/0474) on November 20, 2013.     

Tinnitus distress is linked to enhanced resting‐state functional connectivity from the limbic system to the auditory cortex

The phantom sound of tinnitus is believed to be triggered by aberrant neural activity in the central auditory pathway, but since this debilitating condition is often associated with emotional distress and anxiety, these comorbidities likely arise from maladaptive functional connections to limbic structures such as the amygdala and hippocampus. To test this hypothesis, resting‐state functional magnetic resonance imaging (fMRI) was used to identify aberrant effective connectivity of the amygdala and hippocampus in tinnitus patients and to determine the relationship with tinnitus characteristics. Chronic tinnitus patients (n = 26) and age‐, sex‐, and education‐matched healthy controls (n = 23) were included. Both groups were comparable for hearing level. Granger causality analysis utilizing the amygdala and hippocampus as seed regions were used to investigate the directional connectivity and the relationship with tinnitus duration or distress. Relative to healthy controls, tinnitus patients demonstrated abnormal directional connectivity of the amygdala and hippocampus, including primary and association auditory cortex, and other non‐auditory areas. Importantly, scores on the Tinnitus Handicap Questionnaires were positively correlated with increased connectivity from the left amygdala to left superior temporal gyrus (r = 0.570, P = 0.005), and from the right amygdala to right superior temporal gyrus (r = 0.487, P = 0.018). Moreover, enhanced effective connectivity from the right hippocampus to left transverse temporal gyrus was correlated with tinnitus duration (r = 0.452, P = 0.030). The results showed that tinnitus distress strongly correlates with enhanced effective connectivity that is directed from the amygdala to the auditory cortex. The longer the phantom sensation, the more likely acute tinnitus becomes permanently encoded by memory traces in the hippocampus. Hum Brain Mapp 38:2384–2397, 2017. © 2017 Wiley Periodicals, Inc.     

Neurobehavioral and autonomic alterations in adults with obstructive sleep apnea

ObjectiveObstructive sleep apnea (OSA) is associated with sympathetic hyperactivity, excessive nocturnal sweating, sleepiness, and neurobehavioral cognitive alterations. However, it is not well known if cognitive consequences of OSA are independent from autonomic alterations. Thus, we assessed the association between polysomnographic, autonomic, and cognitive tests performance in OSA patients.MethodsFifty eight OSA patients (53 male) were administered with questionnaires assessing demographic, Epworth, Beck Depression Inventory, Syndrom Kurz test (SKT), Trail Making part B (TMT-B), and Frontal Assessment Battery (FAB) tests. Spectral analysis of heart rate variability (HRV) and night sweating symptoms (NSwS) score were used to assess autonomic function.ResultsGlobal cognitive function (SKT) was normal in mild-moderate (M-OSA) and severe (S-OSA) patients. In S-OSA patients AHI was correlated with TMT-B (r = 0.30 P < 0.05) and with FAB (r = −0.31 P < 0.05). Oxygen desaturation was correlated with TMT-B (r = −0.45 P = < 0.001) and FAB (r = 0.29 P = < 0.05). Sympathetic overactivity was correlated with oxygen desaturation: HRV (r = −0.39 P < 0.05) and NSwS score (r = −0.49 P < 0.01), but HRV and NSwS score were not correlated with TMT-B and FAB.ConclusionFrontal cognitive dysfunction and predominance of sympathetic drive occur in OSA patients. Abnormal frontal cognitive function and sympathetic hyperactivity were related to oxygen desaturation, but not between each other. We conclude that neurobehavioral changes and autonomic imbalance in OSA patients take place independently from each other, suggesting different pathophysiological pathways.     

Cognitive state following mild stroke: A matter of hippocampal mean diffusivity

The hippocampus is known to play a vital role in learning and memory and was demonstrated as an early imaging marker for Alzheimer's disease (AD). However, its role as a predictor for mild cognitive impairment and dementia following stroke is unclear. The main purpose of this study was to examine the associations between hippocampal volume, mean diffusivity (MD) and connectivity and cognitive state following stroke. Eighty three consecutive first ever mild to moderate stroke or transient ischemic attack (TIA) survivors from our ongoing prospective TABASCO (Tel Aviv Brain Acute Stroke Cohort) study underwent magnetic resonance imaging scans within 7 days of stroke onset. Hippocampal volume was measured from T1 weighted images, hippocampal mean diffusivity was calculated from diffusion tensor imaging and connectivity was calculated from resting state fMRI. Global cognitive assessments were evaluated during hospitalization and 6 and 12 months later using a computerized neuropsychological battery. Multiple linear regression analysis was used to test which of the hippocampi measurements best predict cognitive state. All three imaging parameters were significantly correlated to each other (|r's| >0.3, P's < 0.005), and with cognitive state 6 and 12 months after the event. Multiple regression analyses demonstrated the predictive role of hippocampal mean diffusivity (β = ?0.382, P = 0.026) on cognitive state, above and beyond that of volume and connectivity of this structure. To our knowledge, the combination of hippocampal volume, mean diffusivity and connectivity in first ever post stroke or TIA patients has not yet been considered in relation to cognitive state. The results demonstrate the predictive role of hippocampal mean diffusivity, suggesting that these changes may precede and contribute to volumetric and connectivity changes in the hippocampi, potentially serving as a marker for early identification of patients at risk of developing cognitive impairment or dementia. © 2015 Wiley Periodicals, Inc.     

Hippocampal structural and functional changes associated with electroconvulsive therapy response

Previous animal models and structural imaging investigations have linked hippocampal neuroplasticity to electroconvulsive therapy (ECT) response, but the relationship between changes in hippocampal volume and temporal coherence in the context of ECT response is unknown. We hypothesized that ECT response would increase both hippocampal resting-state functional magnetic resonance imaging connectivity and hippocampal volumes. Patients with major depressive disorder (n=19) were scanned before and after the ECT series. Healthy, demographically matched comparisons (n=20) were scanned at one-time interval. Longitudinal changes in functional connectivity of hippocampal regions and volumes of hippocampal subfields were compared with reductions in ratings of depressive symptoms. Right hippocampal connectivity increased (normalized) after the ECT series and correlated with depressive symptom reduction. Similarly, the volumes of the right hippocampal cornu ammonis (CA2/3), dentate gyrus and subiculum regions increased, but the hippocampal subfields were unchanged relative to the comparison group. Connectivity changes were not evident in the left hippocampus, and volume changes were limited to the left CA2/3 subfields. The laterality of the right hippocampal functional connectivity and volume increases may be related to stimulus delivery method, which was predominately right unilateral in this investigation. The findings suggested that increased hippocampal functional connectivity and volumes may be biomarkers for ECT response.     

Relation between functional connectivity and disability in multiple sclerosis: a non-linear model

Objective

To characterize the relation between brain functional connectivity and disability in patients with multiple sclerosis; to investigate the existence of critical values of both disability and functional connectivity corresponding to exhaustion of functional adaptive mechanisms.

Methods

Hundred-and-nineteen patients with no-to-severe disability and 42 healthy subjects were studied via 3T resting state functional MRI. Out of 116 regions extracted from Automated Anatomical Labeling atlas, pairs of regions whose functional connectivity correlated with Expanded Disability Status Score were identified. In patients, mathematical modeling was applied to find the best models describing Expanded-Disability-Status-Score vs structural or functional measures. Functional vs structural models intersecting points were identified.

Results

Disability had direct linear relation with lesion load (r?=?0.40, p?<?5E?6), inverse of thalamic volume (r?=?0.31 p?<?1E?3) and functional connectivity in bi-frontal pairs of regions (r?>?0.40, p?<?0.04), while being non-linearly associated with functional connectivity in cerebello-temporal and cerebello-frontal pairs of regions (F?>?1.73, p?<?0.02). Structural vs functional models intersecting points corresponded to Expanded Disability Status Score of 3.0. 85% of patients scoring more than 3.0 showed functional connectivity in cerebello-temporal and cerebello-frontal pairs of regions below confidence intervals (z?=?[2.28–2.88] 95% CI) measured in healthy subjects.

Conclusions

Functional brain connectivity changes may represent mechanisms of adaptation to structural damage and inflammation and may be not always clinically beneficial. Functional connectivity decreases in comparison with structural measure at Expanded Disability Status Score greater than 3.0, which may be critical and indicate exhaustion of compensatory mechanisms.

     

Cortical N-acetyl aspartate is a predictor of long-term clinical disability in multiple sclerosis

Abstract

Objective:

To evaluate the prognostic value of the cortical N-acetyl aspartate to creatine ratio (NAA/Cr) in early relapsing-remitting multiple sclerosis (RRMS).

Methods:

Sixteen patients with newly diagnosed RRMS were studied by serial MRI and MR spectroscopic imaging (MRSI) once every 6 months for 24 months. Clinical examinations, including the expanded disability status scale (EDSS), were performed at baseline, month 24, and at year 7.

Results:

Baseline cortical NAA/Cr correlated inversely with EDSS at month 24 (r = ?0·61, P < 0·05), and patients with EDSS ≧ 4 had a lower baseline cortical NAA/Cr compared to those with EDSS less than 4 (P < 0·05). Baseline cortical NAA/Cr also correlated inversely with EDSS at the 7-year follow-up (r = ?0·56, P < 0·05), and patients with EDSS ≧ 4 had a lower baseline cortical NAA/Cr compared to those with EDSS less than 4 (P < 0·05).

Baseline brain parenchymal fraction (BPF) correlated inversely with EDSS at month 24 (r = ?0·61, P < 0·05), but not with EDSS at year 7.

Discussion:

Cortical NAA/Cr in early RRMS correlated with clinical disability after 2 and 7 years and may be used as a predictor of long-term disease outcome.     

Amygdala Connectivity Differs Among Chronic,Early Course,and Individuals at Risk for Developing Schizophrenia

Alterations in circuits involving the amygdala have been repeatedly implicated in schizophrenia neuropathology, given their role in stress, affective salience processing, and psychosis onset. Disturbances in amygdala whole-brain functional connectivity associated with schizophrenia have yet to be fully characterized despite their importance in psychosis. Moreover, it remains unknown if there are functional alterations in amygdala circuits across illness phases. To evaluate this possibility, we compared whole-brain amygdala connectivity in healthy comparison subjects (HCS), individuals at high risk (HR) for schizophrenia, individuals in the early course of schizophrenia (EC-SCZ), and patients with chronic schizophrenia (C-SCZ). We computed whole-brain resting-state connectivity using functional magnetic resonance imaging at 3T via anatomically defined individual-specific amygdala seeds. We identified significant alterations in amygdala connectivity with orbitofrontal cortex (OFC), driven by reductions in EC-SCZ and C-SCZ (effect sizes of 1.0 and 0.97, respectively), but not in HR for schizophrenia, relative to HCS. Reduced amygdala-OFC coupling was associated with schizophrenia symptom severity (r = .32, P < .015). Conversely, we identified a robust increase in amygdala connectivity with a brainstem region around noradrenergic arousal nuclei, particularly for HR individuals relative to HCS (effect size = 1.54), but not as prominently for other clinical groups. These results suggest that deficits in amygdala-OFC coupling could emerge during the initial episode of schizophrenia (EC-SCZ) and may present as an enduring feature of the illness (C-SCZ) in association with symptom severity but are not present in individuals with elevated risk for developing schizophrenia. Instead, in HR individuals, there appears to be increased connectivity in a circuit implicated in stress response.Key words: schizophrenia, prefrontal cortex, amygdala, connectivity, first episode, risk for schizophrenia     

Midlife managerial experience is linked to late life hippocampal morphology and function

An active cognitive lifestyle has been suggested to have a protective role in the long-term maintenance of cognition. Amongst healthy older adults, more managerial or supervisory experiences in midlife are linked to a slower hippocampal atrophy rate in late life. Yet whether similar links exist in individuals with Mild Cognitive Impairment (MCI) is not known, nor whether these differences have any functional implications. 68 volunteers from the Sydney SMART Trial, diagnosed with non-amnestic MCI, were divided into high and low managerial experience (HME/LME) during their working life. All participants underwent neuropsychological testing, structural and resting-state functional MRI. Group comparisons were performed on hippocampal volume, morphology, hippocampal seed-based functional connectivity, memory and executive function and self-ratings of memory proficiency. HME was linked to better memory function (p?=?0.024), mediated by larger hippocampal volume (p?=?0.025). More specifically, deformation analysis found HME had relatively more volume in the CA1 sub-region of the hippocampus (p?<?0.05). Paradoxically, this group rated their memory proficiency worse (p?=?0.004), a result correlated with diminished functional connectivity between the right hippocampus and right prefrontal cortex (p?<?0.001). Finally, hierarchical regression modelling substantiated this double dissociation.     

血清S100B蛋白抗脑抗体海马体积变化与阿尔茨海默病患者认知功能变化的关系

目的探讨血清S100B蛋白、抗脑抗体(ABAb)、海马体积大小变化与阿尔茨海默病(AD)患者认知功能变化的关系。方法选取濮阳市油田总医院确诊的88例阿尔茨海默病患者(AD组),选取正常体检者90例为对照组,检测并对比2组血清S100B蛋白、ABAb、海马体积,采用线性相关、多元线性回归分析各项研究指标与简易精神状态量表(MMSE)的相关性。结果AD组血清S100B蛋白、ABAb测定值均高于对照组(P<0.05);AD组海马体积、MMSE评分均低于对照组(P<0.05);AD组血清S100B蛋白、ABAb测定值与MMSE评分呈负相关性(P<0.05);AD组海马体积与MMSE评分呈正相关性(P<0.05);多元线性回归模型显示,血清S100B蛋白、ABAb增高与AD患者MMSE评分呈负相关(P<0.05),海马体积、受教育年限与MMSE评分呈正相关(P<0.05)。结论AD患者的血清S100B蛋白、ABAb增高,海马体积较健康人群降低,且与患者认知功能受损程度有关。     

1H magnetic resonance spectroscopy of chronic cerebral white matter lesions and normal appearing white matter in multiple sclerosis

OBJECTIVES—To test the hypothesis that irrecoverable neurological deficit in multiple sclerosis is associated with axonal loss.
METHODS—¹H magnetic resonance spectroscopy (MRS) was carried out in a group of patients with clinically definite multiple sclerosis (n=31).
Using this technique, the apparent concentration of NA ([NA] the sum of N-acetyl aspartate (NAA), a neuronal marker, and N-acetylaspartylglutamate has been compared in four groups of patients with multiple sclerosis classified as relapsing-remitting, secondary progressive, primary progressive, benign, and a control group.
RESULTS—In the patients with relapsing-remitting disease (n=9) there was a highly significant reduction of apparent NA (median 8.73mM, range 6.86 mM-10.74 mM, P=0.0008) from an area of high signal compared with the control group (median 11.97 mM, range 10.55mM-14.5 mM). In the patients with secondary progressive disease (n=10), there was again a highly significant reduction of apparent NA (median 7.82 mM, range 3.5 mM-10.3 mM, P=0.0003) from an area of high signal compared with the control group. In the patients with primary progressive disease (n=6) there was once again a highly significant reduction of apparent NA (median 8.83 mM, range 6.95 mM-9.89 mM, P<0.002) from an area of high signal compared with the control group. In the patients with benign disease, however, there was no significant difference in the apparent NA (median 10.5 mM, range 8.53 mM-12.8 mM, P>0.05) from an area of high signal compared with the control group. In the patients with benign disease (n=5) there was also no significant difference in the apparent NA (median 10.74 mM, range 8.58 mM-13.4 mM, P>0.3) from an area of normal appearing white matter compared with the control group. In the patients with primary progressive disease, however, there was a significant reduction of apparent NA from an area of normal appearing white matter (median 8.78 mM, range 8.7 mM-12.38 mM, P< 0.025) compared with the control group. There was a significant inverse correlation between [NA] from lesions in the patients with multiple sclerosis and disability as measured on the Kurtzke expanded disability scale score (r= -0.364, 0.05>P> 0.02).
CONCLUSION—These findings support the hypothesis that axonal loss is important in the development of disability in multiple sclerosis. They also provide evidence for axonal loss in normal appearing white matter in patients with primary progressive disease.

     

Impact of regional white matter lesions on cognitive function in subcortical vascular cognitive impairment

Abstract

Objectives:

Exact characterization and localization of white matter lesions (WMLs) as they relate and contribute to vascular cognitive impairment is highly debated. The purpose of this study was to investigate the impact of WML on cognitive function by using a new anatomy-based classification method.

Methods:

We detected WML accurately by using a three-dimensional fluid-attenuated inversion recovery (3D FLAIR) imaging technique and subsequently segmented WMLs by using an anatomy-based method. Participants included 56 consecutive patients diagnosed with subcortical vascular cognitive impairment (SubVCI). The volume of WMLs in different anatomic regions was measured. The volume of the hippocampus, the corpus callosum (CC), any lacunar infarcts, total gray matter (GM), and total brain volumes were also calculated.

Results:

Hippocampal (P = 0·005) as well as temporal WML volumes (P = 0·039) were both independently associated with mini-mental state examination (MMSE) score. Only the parietal WML volume (P = 0·000) was independently associated with Montreal Cognitive Assessment (MoCA) score. Frontal WMLs were independently correlated with executive function. Occipital WMLs were independently associated with visuospatial and recall function. Language impairment was independently correlated with both parietal GM and parietal WML volume. Functions related to orientation were independently associated with parietal WML volume.

Discussion:

The volume of WMLs in the temporal region as well as in the hippocampus were both independently associated with MMSE score. For the MoCA score, however, only parietal WML volumes were independently correlated. White matter lesions within different anatomic regions were separately correlated with different subdomains of cognitive function.     

Mechanism of visual network dysfunction in relapsing-remitting multiple sclerosis and its relation to cognition

ObjectiveTo investigate if changes in brain network function and connectivity contribute to the abnormalities in visual event related potentials (ERP) in relapsing-remitting multiple sclerosis (RRMS), and explore their relation to a decrease in cognitive performance.MethodsWe evaluated 72 patients with RRMS and 89 healthy control subjects in a cross-sectional study. Visual ERP were generated using illusory and non-illusory stimuli and recorded using 21 EEG scalp electrodes. The measured activity was modelled using Dynamic Causal Modelling. The model network consisted of 4 symmetric nodes including the primary visual cortex (V1/V2) and the Lateral Occipital Complex. Patients and controls were tested with a neuropsychological test battery consisting of 18 cognitive tests covering six cognitive domains.ResultsWe found reduced cortical connectivity in bottom-up and interhemispheric connections to the right lateral occipital complex in patients (p < 0.001). Furthermore, interhemispherical connections were related to cognitive dysfunction in several domains (attention, executive function, visual perception and organization, processing speed and global cognition) for patients (p < 0.05). No relation was seen between cortical network connectivity and cognitive function in the healthy control subjects.ConclusionChanges in the functional connectivity to higher cortical regions provide a neurobiological explanation for the changes of the visual ERP in RRMS.SignificanceThis study suggests that changes in connectivity to higher cortical regions partly explain visual network dysfunction in RRMS where a lower interhemispheric connectivity may contribute to impaired cognitive function.     

The effect of natalizumab on cognitive function in patients with relapsing-remitting multiple sclerosis: preliminary results of a 1-year follow-up study

The objective of the study was to assess the natalizumab effect on the course of cognitive impairment in patients with relapsing-remitting multiple sclerosis (MS). Patients with active relapsing-remitting MS (n = 17) were treated with natalizumab for 1 year. The quasi control group included patients (n = 7) with clinically stable MS. Assessment of disease course [expanded disability status scale (EDSS); number of relapses] and neuropsychological impairment [Wisconsin card sorting test (WCST); controlled oral word associations; verbal/non-verbal memory tests; paced auditory serial addition test] was conducted at baseline and after 1 year. Natalizumab-treated patients experienced significantly fewer relapses compared with the previous year (P < 0.05). At 1-year follow-up, EDSS score was unchanged and neuropsychological assessments of memory/executive functions showed a significant improvement in natalizumab-treated patients (all P < 0.05). No changes were observed in the quasi control group. This preliminary study suggests that natalizumab could be effective in ameliorating cognitive functions in patients with active relapsing-remitting MS, over 1-year follow-up.