Corpus callosum atrophy is strongly associated with cognitive impairment in multiple sclerosis: Results of a 17-year longitudinal study

Background: Cognitive impairment is common in multiple sclerosis (MS) and may be subtle. The corpus callosum is essential for connectivity-demanding cognitive tasks and is significantly affected in MS, therefore it may serve as a marker for cognitive function. Objective: The objective of this paper is to longitudinally study the normalized corpus callosum area (nCCA) as a marker of cognitive function and disability in MS. Methods: Thirty-seven MS patients were followed from 1996 with follow-ups in 2004 and 2013. A healthy matched control group was recruited. The Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test (SDMT) were assessed. The nCCA was measured on T2-weighted images. Volumetry was performed with FreeSurfer. Results: Disease duration spanned five decades (1.6–46 years). Annual corpus callosal atrophy rate decreased with disease duration. nCCA was strongly correlated with SDMT ( r = 0.793, p < 0.001) and moderately correlated with EDSS ( r = −0.545, p < 0.001) after adjusting for disease duration, age and sex. The correlations of brain parenchymal fraction, white matter fraction, gray matter fraction and normalized lesion volume were less strong. Conclusions: The nCCA correlates well with physical and cognitive disability in time perspectives close to two decades, outperforming volumetric measurements. The nCCA is fast and could be feasible for clinical implementation where it may help identify patients in need of neuropsychological evaluation.

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The relationship between total and regional corpus callosum atrophy, cognitive impairment and fatigue in multiple sclerosis patients

Multiple Sclerosis Journal ◽

10.1177/1352458513496880 ◽

2013 ◽

Vol 20 (3) ◽

pp. 356-364 ◽

Cited By ~ 51

Author(s):

Özgür Yaldizli ◽

Iris-Katharina Penner ◽

Karl Frontzek ◽

Yvonne Naegelin ◽

Michael Amann ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cognitive Impairment ◽

Corpus Callosum ◽

Disease Duration ◽

Brain Magnetic Resonance Imaging ◽

Lesion Volume ◽

Poor Outcome ◽

Edss Score ◽

Multiple Sclerosis Patients ◽

The Relationship

Objective: The objective of this paper is to investigate the relationship between total and regional corpus callosum (CC) atrophy, neuropsychological test performance and fatigue in multiple sclerosis (MS) patients. Methods: We conducted a cross-sectional study in 113 MS patients: mean age 48±11 years, 75/113 women, 84/113 relapsing–remitting MS, mean disease duration 21±9 years, mean Expanded Disability Status Scale (EDSS) score 3.2±1.7. All patients underwent brain magnetic resonance imaging, standardised neurological assessment and comprehensive cognitive testing including assessments for fatigue and depression. Total and regional CC atrophy was assessed using the corpus callosum index (CCI). Results: CCI correlated more strongly with T2- and T1-lesion volume and whole brain volume than with disease duration or EDSS score. CCI correlated strongly with the verbal fluency test (VFT), Symbol Digit Modalities Test (SDMT) and Paced Auditory Serial Addition Test (PASAT). Multivariate regression analysis revealed that atrophy of the posterior CC segment was significantly associated with poor outcome in the PASAT, VFT and SDMT. In contrast, atrophy of the anterior CC segment was significantly associated with fatigue severity and poor outcome in the long-term memory test. Conclusions: Atrophy of the CC is associated with cognitive impairment and fatigue. Regional CCI results indicate that these associations are partially spatially segregated.

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T1 cortical hypointensities and their association with cognitive disability in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458510377223 ◽

2010 ◽

Vol 16 (10) ◽

pp. 1203-1212 ◽

Cited By ~ 16

Author(s):

Francesca Bagnato ◽

Zeena Salman ◽

Robert Kane ◽

Sungyoung Auh ◽

Fredric K Cantor ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cognitive Impairment ◽

White Matter ◽

Statistical Significance ◽

Verbal Learning ◽

Lesion Volume ◽

Cognitive Disability ◽

3.0 Tesla ◽

Multiple Sclerosis Patients ◽

The Impact

Background: Neocortical lesions (NLs) largely contribute to the pathology of multiple sclerosis (MS), although their relevance in patients’ disability remains unknown. Objective: To assess the incidence of T1 hypointense NLs by 3.0-Tesla magnetic resonance imaging (MRI) in patients with MS and examine neocortical lesion association with cognitive impairment. Methods: In this case-control study, 21 MS patients and 21 age-, sex- and years of education-matched healthy volunteers underwent: (i) a neuropsychological examination rating cognitive impairment (Minimal Assessment of Cognitive Function in MS); (ii) a 3.0-Tesla MRI inclusive of an isotropic 1.0 mm3 three-dimensional inversion prepared spoiled gradient-recalled-echo (3D-IRSPGR) image and T1- and T2-weighted images. Hypointensities on 3D-IRSPGR lying in the cortex, either entirely or partially were counted and association between NLs and cognitive impairment investigated. Results: A total of 95 NLs were observed in 14 (66.7%) patients. NL+ patients performed poorer (p = 0.020) than NLpatients only on the delayed recall component of the California Verbal Learning Test. This difference lost statistical significance when a correction for white matter lesion volume was employed. Conclusions: Although T 1 hypointense NLs may be present in a relatively high proportion of multiple sclerosis patients, the impact that they have in cognitive impairment is not independent from white matter disease.

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Conventional and Quantitative Magnetic Resonance Imaging and Cognitive Impairment in Multiple Sclerosis

European Neurological Review ◽

10.17925/enr.2009.04.02.70 ◽

2009 ◽

Vol 4 (2) ◽

pp. 70

Author(s):

Christopher R Tench ◽

Cris S Constantinescu ◽

◽

Keyword(s):

Magnetic Resonance Imaging ◽

Multiple Sclerosis ◽

Cognitive Impairment ◽

Cognitive Function ◽

Magnetic Resonance ◽

Quantitative Mri ◽

Lesion Volume ◽

Resonance Imaging ◽

Information Processing Speed ◽

Conventional Mri

An estimated 30–70% of patients with multiple sclerosis (MS) have some cognitive impairment. Cognitive function depends on a spectrum of faculties including information processing speed, sustained attention, recent memory and executive function. The broad definition of cognition has resulted in different assessments of function, and repeatable batteries of tests have been devised to gain an overall and repeatable view of cognition in MS. Many studies have attempted to find an association between cognitive function and MS pathology using magnetic resonance imaging (MRI). Conventional MRI has been used to show the relationship between cognitive impairment and MS lesion volume and/or brain volume (reflecting atrophy). Studies using quantitative MRI to estimate the degree of abnormality in tissue that is normal-appearing on conventional MRI have also found correlations with cognitive function. Longitudinally, cognitive decline has been found to correlate with changing MRI-detectable pathology in some studies. However, consistency between studies has been lacking, and the large number of cognitive tests available makes direct comparison of different studies difficult. Focus on specific cognitive domains may alleviate this issue in future studies.

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Changes in Cerebrospinal Fluid Balance of TNF and TNF Receptors in Naïve Multiple Sclerosis Patients: Early Involvement in Compartmentalised Intrathecal Inflammation

Cells ◽

10.3390/cells10071712 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1712

Author(s):

Roberta Magliozzi ◽

Francesco Pezzini ◽

Mairi Pucci ◽

Stefania Rossi ◽

Francesco Facchiano ◽

...

Keyword(s):

Multiple Sclerosis ◽

Immune Cell ◽

Protein Pattern ◽

Fold Change ◽

Cortical Lesion ◽

Control Group ◽

Lesion Volume ◽

Mri Features ◽

Csf Levels ◽

Multiple Sclerosis Patients

An imbalance of TNF signalling in the inflammatory milieu generated by meningeal immune cell infiltrates in the subarachnoid space in multiple sclerosis (MS), and its animal model may lead to increased cortical pathology. In order to explore whether this feature may be present from the early stages of MS and may be associated with the clinical outcome, the protein levels of TNF, sTNF-R1 and sTNF-R2 were assayed in CSF collected from 122 treatment-naïve MS patients and 36 subjects with other neurological conditions at diagnosis. Potential correlations with other CSF cytokines/chemokines and with clinical and imaging parameters at diagnosis (T0) and after 2 years of follow-up (T24) were evaluated. Significantly increased levels of TNF (fold change: 7.739; p < 0.001), sTNF-R1 (fold change: 1.693; p < 0.001) and sTNF-R2 (fold change: 2.189; p < 0.001) were detected in CSF of MS patients compared to the control group at T0. Increased TNF levels in CSF were significantly (p < 0.01) associated with increased EDSS change (r = 0.43), relapses (r = 0.48) and the appearance of white matter lesions (r = 0.49). CSF levels of TNFR1 were associated with cortical lesion volume (r = 0.41) at T0, as well as with new cortical lesions (r = 0.56), whilst no correlation could be found between TNFR2 levels in CSF and clinical or MRI features. Combined correlation and pathway analysis (ingenuity) of the CSF protein pattern associated with TNF expression (encompassing elevated levels of BAFF, IFN-γ, IL-1β, IL-10, IL-8, IL-16, CCL21, haptoglobin and fibrinogen) showed a particular relationship to the interaction between innate and adaptive immune response. The CSF sTNF-R1-associated pattern (encompassing high levels of CXCL13, TWEAK, LIGHT, IL-35, osteopontin, pentraxin-3, sCD163 and chitinase-3-L1) was mainly related to altered T cell and B cell signalling. Finally, the CSF TNFR2-associated pattern (encompassing high CSF levels of IFN-β, IFN-λ2, sIL-6Rα) was linked to Th cell differentiation and regulatory cytokine signalling. In conclusion, dysregulation of TNF and TNF-R1/2 pathways associates with specific clinical/MRI profiles and can be identified at a very early stage in MS patients, at the time of diagnosis, contributing to the prediction of the disease outcome.

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Study of cognitive functions in major idiopathic interstitial pneumonias

Egyptian Journal of Bronchology ◽

10.1186/s43168-020-00046-7 ◽

2020 ◽

Vol 14 (1) ◽

Author(s):

Mohamed W. Zakaria ◽

Reem I. El-Korashy ◽

Mostafa O. Shaheen ◽

Samah Selim ◽

Kwashi J. Amum

Keyword(s):

Cognitive Impairment ◽

Cognitive Function ◽

Cognitive Dysfunction ◽

Mini Mental State Examination ◽

Mmse Score ◽

Control Group ◽

Healthy Individuals ◽

Co Morbidity ◽

Impaired Lung Function ◽

State Examination

Abstract Background Cognitive dysfunction in idiopathic interstitial pneumonia (IIP) is an important clinical co-morbidity that is associated with impaired lung function. The aim of the work is to assess cognitive function in major IIP and to find out the relation between cognitive dysfunction and the oxygenation parameters. Results Fifty individuals were involved in the study; 30 patients with major IIP and 20 healthy individuals. Patients with IIP had significantly lower mini mental state examination (MMSE) score compared to the control group (P < 0.001). Wechsler Deterioration Index (WDI) revealed that 33.3% (n = 10) of the patients with IIP had sure cognitive impairment and 26.6% (n = 8) had ongoing cognitive deterioration. Patients with idiopathic pulmonary fibrosis (IPF) had lower cognitive function than other IIP. Conclusion There is an impairment of cognitive function in patients with major IIP, particularly in IPF, as measured by WDI and MMSE. Further large studies are needed to assess the possible predictors of cognitive impairment and their effects on the patients’ outcome.

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Evaluation of the effects of group psychotherapy on cognitive function in patients with multiple sclerosis with cognitive dysfunction and depression

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20140144 ◽

2015 ◽

Vol 73 (2) ◽

pp. 90-95 ◽

Cited By ~ 3

Author(s):

Emine Bilgi ◽

Hasan Hüseyin Özdemir ◽

Ayhan Bingol ◽

Serpil Bulut

Keyword(s):

Multiple Sclerosis ◽

Cognitive Impairment ◽

Cognitive Function ◽

Group Psychotherapy ◽

Cognitive Dysfunction ◽

Beck Depression Inventory ◽

Neuropsychological Tests ◽

Depression Severity ◽

Group Members ◽

Repeatable Battery

Objective This study will evaluate how decreasing depression severity via group psychotherapy affects the cognitive function of patients with multiple sclerosis (MS) who are also diagnosed with depression and cognitive dysfunction. Method MS patients completed the Brief Repeatable Battery of Neuropsychological Tests and Beck Depression Inventory (BDI). The group members diagnosed with depression and cognitive dysfunction underwent group psychotherapy for 3 months. Upon completion of psychotherapy, both tests were readministered. Results Depression and cognitive dysfunction were comorbid in 15 (13.9%) of patients. Although improvement was detected at the end of the 3-month group psychotherapy intervention, it was limited to the BDI and the Paced Auditory Test. Conclusion Group psychotherapy might decrease cognitive impairment in MS patients.

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Validity and Reliability of Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) in Indonesia and the Correlation with Quality of Life

Neurology Research International ◽

10.1155/2019/4290352 ◽

2019 ◽

Vol 2019 ◽

pp. 1-7

Author(s):

Riwanti Estiasari ◽

Yuhyi Fajrina ◽

Diatri Nari Lastri ◽

Syarli Melani ◽

Kartika Maharani ◽

...

Keyword(s):

Quality Of Life ◽

Multiple Sclerosis ◽

Cognitive Impairment ◽

Cognitive Function ◽

Cognitive Assessment ◽

Verbal Learning ◽

Retest Reliability ◽

Cognitive Evaluation ◽

Test Retest Reliability

Introduction. Multiple Sclerosis (MS) can affect cognitive function that might interfere with quality of life. Processing speed and memory are the most common area of cognitive impairment. Cognitive evaluation in daily practice is often difficult to be performed since it needs neuropsychological expert and is time-consuming. Brief International Cognitive Assessment for MS (BICAMS) is valid and practical for cognitive evaluation. This study aims to validate BICAMS in Indonesian MS patients and healthy controls (HC) and to analyse the effect of cognitive impairment on quality of life. Methods. BICAMS, which composes Symbol Digits Modalities Test (SDMT), California Verbal Learning Test-Second Edition (CVLT-II), and Brief Visuospatial Memory Test-Revised (BVMT-R), was translated and cross-culturally adapted to Indonesian from the original BICAMS and then administered to 40 Indonesian MS patients and 66 HC matched by sex, age, and education. Test-retest reliability was performed on 16-MS patients and 42 HC. Quality of life was measured using Multiple Sclerosis Quality of Life (MSQOL-54) instrument. Results. The SDMT, CVLT-II, and BVMT-R score in MS patients were significantly lower than those in HC (effect size, r: 0.61, 0.36, and 0.47, respectively). Test-retest reliability for all tests was satisfactory with correlation coefficient for SDMT, CVLT-II, and BVMT-R in MS subjects 0.86, 0.81, and 0.83, respectively. Using 5th percentile of HC score as cut-off, 15% MS subjects had impairment in one test, 27.5% in two tests, and 40% in three tests. BICAMS was moderately correlated with EDSS but was not correlated with disease duration and relapse rate. SDMT score correlated with physical function and physical and mental role limitation. Conclusion. BICAMS is valid and reliable for assessing cognitive function of Indonesia MS patients.

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Gray matter trophism, cognitive impairment, and depression in patients with multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458517692886 ◽

2017 ◽

Vol 23 (14) ◽

pp. 1864-1874 ◽

Cited By ~ 24

Author(s):

Emanuele Pravatà ◽

Maria A Rocca ◽

Paola Valsasina ◽

Gianna C Riccitelli ◽

Claudio Gobbi ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cognitive Impairment ◽

Gray Matter ◽

Rating Scale ◽

Three Dimensional ◽

Emotional Behavior ◽

Cortical Atrophy ◽

Lesion Volume ◽

Cortical Thinning ◽

C Statistic

Background: Cognitive impairment and depression frequently affects patients with multiple sclerosis (MS). However, the relationship between the occurrence of depression and cognitive impairment and the development of cortical atrophy has not been fully elucidated yet. Objectives: To investigate the association of cortical and deep gray matter (GM) volume with depression and cognitive impairment in MS. Methods: Three-dimensional (3D) T1-weighted scans were obtained from 126 MS patients and 59 matched healthy controls. Cognitive impairment was assessed using the Brief Repeatable Battery of Neuropsychological Tests and depression with the Montgomery-Asberg Depression Rating Scale (MADRS). Using FreeSurfer and FIRST software, we assessed cortical thickness (CTh) and deep GM volumetry. Magnetic resonance imaging (MRI) variables explaining depression and cognitive impairment were investigated using factorial and classification analysis. Multivariate regression models correlated GM abnormalities with symptoms severity. Results: Compared with controls, MS patients exhibited widespread bilateral cortical thinning involving all brain lobes. Depressed MS showed selective CTh decrease in fronto-temporal regions, whereas cognitive impairment MS exhibited widespread fronto-parietal cortical and subcortical GM atrophy. Frontal cortical thinning was the best predictor of depression ( C-statistic = 0.7), whereas thinning of the right precuneus and high T2 lesion volume best predicted cognitive impairment ( C-statistic = 0.8). MADRS severity correlated with right entorhinal cortex thinning, whereas cognitive impairment severity correlated with left entorhinal and thalamus atrophy. Conclusion: MS-related depression is linked to circumscribed CTh changes in areas deputed to emotional behavior, whereas cognitive impairment is correlated with cortical and subcortical GM atrophy of circuits involved in cognition.

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Effect of Baduanjin exercise on cognitive function in patients with post-stroke cognitive impairment: a randomized controlled trial

Clinical Rehabilitation ◽

10.1177/0269215520930256 ◽

2020 ◽

Vol 34 (8) ◽

pp. 1028-1039 ◽

Cited By ~ 2

Author(s):

Guohua Zheng ◽

Yuhui Zheng ◽

Zhenyu Xiong ◽

Bingzhao Ye

Keyword(s):

Cognitive Impairment ◽

Cognitive Function ◽

Outcome Measures ◽

Daily Living ◽

Controlled Trial ◽

Secondary Outcome ◽

Control Group ◽

Rehabilitation Treatment ◽

Global Cognitive Function ◽

Delayed Recognition

Objective: To investigate the effectiveness and safety of Baduanjin training on the cognitive function in stroke survivors with cognitive impairment. Design: A randomized, two-arm parallel controlled trial with allocation concealment and assessors blinding. Setting: Community centre of Fuzhou city, China. Subjects: A total of 48 participants were recruited and randomly allocated into the Baduanjin exercise intervention or control group. Interventions: The control group maintained original medication and rehabilitation treatment. The Baduanjin training group received 24-week Baduanjin training with a frequency of three days a week and 40 minutes a day based on original medication and rehabilitation treatment. Main outcome measures: The primary outcome was global cognitive function. Secondary outcome measures included the specific domains of cognition (i.e. memory, processing speed, execution, attention and visuospatial ability) and activities daily living. Results: In total, 41 (Baduanjin n = 22, control n = 19) participants completed 24-week treatment and data collection. Mean differences between groups at 24-week treatment were statistically significant for global cognitive function (MoCA: 2.54 (0.91 to 4.16)), execution (TMT-A: −42.4 (−75.0 to −9.8); TMT-B: −71.3 (−130.6 to −12.1)), memory (immediate recall: 2.11 (0.49 to 3.73); short-term delayed recognition: 2.47 (0.58 to 4.35) and long-term delayed recognition: 1.68(0.18 to 3.17)), attention (response time of alertness: −245.5 (−387 to −104)) and activities of daily living (modified Barthel Index). Conclusion: Regular Baduanjin training is associated with less loss of cognitive function in patients after stroke.

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Cognitive Impairment in Advanced Chronic Kidney Disease: The Canadian Frailty Observation and Interventions Trial

American Journal of Nephrology ◽

10.1159/000450837 ◽

2016 ◽

Vol 44 (6) ◽

pp. 473-480 ◽

Cited By ~ 22

Author(s):

Rukhsana Foster ◽

Simon Walker ◽

Ranveer Brar ◽

Brett Hiebert ◽

Paul Komenda ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Cognitive Impairment ◽

Cognitive Function ◽

Kidney Disease ◽

High Rate ◽

Control Group ◽

Cross Sectional ◽

History Of ◽

Poor Nutrition

Background: Chronic kidney disease (CKD) affects more than one third of older adults, and is a strong risk factor for vascular disease and cognitive impairment. Cognitive impairment can have detrimental effects on the quality of life through decreased treatment adherence and poor nutrition and results in increased costs of care and early mortality. Though widely studied in hemodialysis populations, little is known about cognitive impairment in patients with pre-dialysis CKD. Methods: Multicenter, cross-sectional, prospective cohort study including 385 patients with CKD stages G4-G5. Cognitive function was measured with a validated tool called the Montreal Cognitive Assessment (MoCA) as part of a comprehensive frailty assessment in the Canadian Frailty Observation and Interventions Trial. Cognitive impairment was defined as a MoCA score of ≤24. We determined the prevalence and risk factors for cognitive impairment in patients with CKD stages G4-G5, not on dialysis. Results: Two hundred and thirty seven participants (61%) with CKD stages G4-G5 had cognitive impairment at baseline assessment. When compared to a control group, this population scored lower in all domains of cognition, with the most pronounced deficits observed in recall, attention, and visual/executive function (p < 0.01 for all comparisons). Older age, recent history of falls and history of stroke were independently associated with cognitive impairment. Conclusions: Our study uncovered a high rate of unrecognized cognitive impairment in an advanced CKD population. This impairment is global, affecting all aspects of cognition and is likely vascular in nature. The longitudinal trajectory of cognitive function and its effect on dialysis decision-making and outcomes deserves further study.

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