Depression and cognitive function in early multiple sclerosis: Multitasking is more sensitive than traditional assessments

2020 ◽  
pp. 135245852095835
Author(s):  
Lisa Glukhovsky ◽  
Daniel Kurz ◽  
Rachel Brandstadter ◽  
Victoria M Leavitt ◽  
Stephen Krieger ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Gray Matter Volume ◽  
Depression Symptoms ◽  
Lesion Volume ◽  
Cognitive Tests ◽  
Healthy Controls ◽  
Mild Depression ◽  
Cognitive Assessments ◽  
Partial Correlations ◽  
Magnetic Resonance Imaging Mri

Background: Persons with multiple sclerosis (MS) and depression symptoms report real-world cognitive difficulties that may be missed by laboratory cognitive tests. Objective: To examine the relationship of depressive symptoms to cognitive monotasking versus multitasking in early MS. Method: Persons with early MS ( n = 185; ⩽5 years diagnosed) reported mood, completed monotasking and multitasking cognitive tests, and received high-resolution 3.0 T magnetic resonance imaging (MRI). Partial correlations analyzed associations between mood and cognition, controlling for age, sex, estimated premorbid IQ, T2 lesion volume, and normalized gray matter volume. Results: Depression symptoms were more related to worse cognitive multitasking (−0.353, p < 0.001) than monotasking ( r = −0.189, p = 0.011). There was a significant albeit weaker link to cognitive efficiency composite score ( r = −0.281, p < 0.001), but not composite memory ( r = −0.036, p > 0.50). Findings were replicated with a second depression measure. Multitasking was worse in patients with at least mild depression than both patients with no/minimal depression and healthy controls. Multitasking was not related to mood in healthy controls. Conclusions: Depression symptoms are linked to cognitive multitasking in early MS; standard monotasking cognitive assessments appear less sensitive to depression-related cognition. Further investigation should determine directionality and mechanisms of this relationship, with the goal of enhancing treatment for cognitive dysfunction and depression in MS.

Association of Age at Onset With Gray Matter Volume and White Matter Microstructural Abnormalities in People With Multiple Sclerosis

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012869
Author(s):  
Raffaello Bonacchi ◽  
Alessandro Meani ◽  
Elisabetta Pagani ◽  
Olga Marchesi ◽  
Andrea Falini ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Gray Matter ◽  
Linear Models ◽  
Gray Matter Volume ◽  
Age At Onset ◽  
Healthy Controls ◽  
Compensatory Mechanisms ◽  
Cross Sectional ◽  
Matter Volume

Objective:To investigate whether age at onset influences brain gray matter volume (GMV) and white matter (WM) microstructural abnormalities in adult multiple sclerosis (MS) patients, given its influence on clinical phenotype and disease course.Method:In this hypothesis-driven cross-sectional study, we enrolled 67 pediatric-onset MS (POMS) patients and 143 sex- and disease duration (DD)-matched randomly-selected adult-onset MS (AOMS) patients, together with 208 healthy controls. All subjects underwent neurological evaluation and 3T MRI acquisition. MRI variables were standardized based on healthy controls, to remove effects of age and sex. Associations with DD in POMS and AOMS patients were studied with linear models. Time to reach clinical and MRI milestones was assessed with product-limit approach.Results:At DD=1 year, GMV and WM fractional anisotropy (FA) were abnormal in AOMS but not in POMS patients. Significant interaction of age at onset (POMS vs AOMS) into the association with DD was found for GMV and WM FA. The crossing point of regression lines in POMS and AOMS patients was at 20 years of DD for GMV and 14 for WM FA. For POMS and AOMS patients, median DD was 29 and 19 years to reach Expanded Disability Status Scale=3 (p<0.001), 31 and 26 years to reach abnormal Paced Auditory Serial Addition Task-3 (p=0.01), 24 and 18 years to reach abnormal GMV (p=0.04), and 19 and 17 years to reach abnormal WM FA (p=0.36).Conclusions:Younger patients are initially resilient to MS-related damage. Then, compensatory mechanisms start failing with loss of WM integrity, followed by GM atrophy and finally disability.

Heterogeneous pathological processes account for thalamic degeneration in multiple sclerosis: Insights from 7 T imaging

2017 ◽  
Vol 24 (11) ◽  
pp. 1433-1444 ◽  
Author(s):  
Céline Louapre ◽  
Sindhuja T Govindarajan ◽  
Costanza Giannì ◽  
Nancy Madigan ◽  
Jacob A Sloane ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Multiple Sclerosis ◽  
Lesion Volume ◽  
Thalamic Lesion ◽  
Cortical Lesions ◽  
Focal Lesions ◽  
Thalamic Degeneration ◽  
Relapsing Remitting ◽  
Thalamic Lesions ◽  
Magnetic Resonance Imaging Mri

Background: Thalamic degeneration impacts multiple sclerosis (MS) prognosis. Objective: To investigate heterogeneous thalamic pathology, its correlation with white matter (WM), cortical lesions and thickness, and as function of distance from cerebrospinal fluid (CSF). Methods: In 41 MS subjects and 17 controls, using 3 and 7 T imaging, we tested for (1) differences in thalamic volume and quantitative T2* (q-T2*) (2) globally and (3) within concentric bands originating from the CSF/thalamus interface; (4) the relation between thalamic, cortical, and WM metrics; and (5) the contribution of magnetic resonance imaging (MRI) metrics to clinical scores. We also assessed MS thalamic lesion distribution as a function of distance from CSF. Results: Thalamic lesions were mainly located next to the ventricles. Thalamic volume was decreased in MS versus controls ( p < 10−2); global q-T2* was longer in secondary progressive multiple sclerosis (SPMS) only ( p < 10−2), indicating myelin and/or iron loss. Thalamic atrophy and longer q-T2* correlated with WM lesion volume ( p < 0.01). In relapsing-remitting MS, q-T2* thalamic abnormalities were located next to the WM ( p < 0.01 (uncorrected), p = 0.09 (corrected)), while they were homogeneously distributed in SPMS. Cortical MRI metrics were the strongest predictors of clinical outcome. Conclusion: Heterogeneous pathological processes affect the thalamus in MS. While focal lesions are likely mainly driven by CSF-mediated factors, overall thalamic degeneration develops in association with WM lesions.

scholarly journals Word-finding difficulty is a prevalent disease-related deficit in early multiple sclerosis

2019 ◽  
Vol 26 (13) ◽  
pp. 1752-1764 ◽  
Author(s):  
Rachel Brandstadter ◽  
Michelle Fabian ◽  
Victoria M Leavitt ◽  
Stephen Krieger ◽  
Anusha Yeshokumar ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Gray Matter ◽  
Objective Assessment ◽  
Lesion Volume ◽  
Healthy Controls ◽  
Patient Report ◽  
Word Finding ◽  
Cognitive Complaint ◽  
Two Samples ◽  
Patient Reported

Background: Persons with multiple sclerosis (MS) commonly report word-finding difficulty clinically, yet this language deficit remains underexplored. Objective: To investigate the prevalence and nature of word-finding difficulty in persons with early MS on three levels: patient report, cognitive substrates, and neuroimaging. Methods: Two samples of early MS patients ( n = 185 and n = 55; ⩽5 years diagnosed) and healthy controls ( n = 50) reported frequency/severity of cognitive deficits and underwent objective assessment with tasks of rapid automatized naming (RAN), measuring lexical access speed, memory, word generation, and cognitive efficiency. High-resolution brain magnetic resonance imaging (MRI) derived measurements of regional cortical thickness, global and deep gray matter volume, and T2 lesion volume. Relationships among patient-reported word-finding difficulty, cognitive performance, and neural correlates were examined. Results: Word-finding difficulty was the most common cognitive complaint of MS patients and the only complaint reported more by patients than healthy controls. Only RAN performance discriminated MS patients with subjective word-finding deficits from those without subjective complaints and from healthy controls. Thinner left parietal cortical gray matter independently predicted impaired RAN performance, driven primarily by the left precuneus. Conclusion: Three levels of evidence (patient-report, objective behavior, regional gray matter) support word-finding difficulty as a prevalent, measurable, disease-related deficit in early MS linked to left parietal cortical thinning.

Relevance of hypointense brain MRI lesions for long-term worsening of clinical disability in relapsing multiple sclerosis

2013 ◽  
Vol 20 (2) ◽  
pp. 214-219 ◽  
Author(s):  
Antonio Giorgio ◽  
Maria Laura Stromillo ◽  
Maria Letizia Bartolozzi ◽  
Francesca Rossi ◽  
Marco Battaglini ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Mri ◽  
Univariate Analysis ◽  
Brain Lesion ◽  
Brain Magnetic Resonance Imaging ◽  
Stepwise Multiple Regression ◽  
Lesion Volume ◽  
Magnetic Resonance Imaging Mri ◽  
Relapsing Remitting Multiple Sclerosis

Background: The accrual of brain focal pathology is considered a good substrate of disability in relapsing–remitting multiple sclerosis (RRMS). However, knowledge on long-term lesion evolution and its relationship with disability progression is poor. Objective: The objective of this paper is to evaluate in RRMS the long-term clinical relevance of brain lesion evolution. Methods: In 58 RRMS patients we acquired, using the same scanner and protocol, brain magnetic resonance imaging (MRI) at baseline and 10±0.5 years later. MRI data were correlated with disability changes as measured by the Expanded Disability Status Scale (EDSS). Results: The annualized 10-year lesion volume (LV) growth was +0.25±0.5 cm3 (+6.7±8.7%) for T2-weighted (T2-W) lesions and +0.20±0.31 cm3 (+11.5±12.3%) for T1-weighted (T1-W) lesions. The univariate analysis showed moderate correlations between baseline MRI measures and EDSS at 10 years ( p < 0.001). Also, 10-year EDSS worsening correlated with LV growth and the number of new/enlarging lesions measured over the same period ( p < 0.005). In the stepwise multiple regression analysis, EDSS worsening over 10 years was best correlated with the combination of baseline T1-W lesion count and increasing T1-W LV ( R = 0.61, p < 0.001). Conclusion: In RRMS patients, long-term brain lesion accrual is associated with worsening in clinical disability. This is particularly true for hypointense, destructive lesions.

scholarly journals Performance of Regression-Based Norms for Cognitive Functioning of Persons With Multiple Sclerosis in an Independent Sample

2021 ◽  
Vol 11 ◽  
Author(s):  
Ruth Ann Marrie ◽  
Christiane E. Whitehouse ◽  
Ronak Patel ◽  
Chase R. Figley ◽  
Jennifer Kornelsen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Relative Efficiency ◽  
Employment Status ◽  
Normative Data ◽  
Healthy Adults ◽  
Cognitive Tests ◽  
Healthy Controls ◽  
Control Groups ◽  
Z Scores ◽  
Healthy Control

Background: Cognitive impairment is common in multiple sclerosis (MS). Interpretation of neuropsychological tests requires the use of normative data. Traditionally, normative data have been reported for discrete categories such as age. More recently continuous norms have been developed using multivariable regression equations that account for multiple demographic factors. Regression-based norms have been developed for use in the Canadian population for tests included in the MACFIMS and BICAMS test batteries. Establishing the generalizability of these norms is essential for application in clinical and research settings.Objectives: We aimed to (i) test the performance of previously published Canadian regression-based norms in an independently collected sample of Canadian healthy controls; (ii) compare the ability of Canadian and non-Canadian regression-based norms to discriminate between healthy controls and persons with MS; and (iii) develop regression-based norms for several cognitive tests drawn from batteries commonly used in MS that incorporated race/ethnicity in addition to age, education, and sex.Methods: We included 93 adults with MS and 96 healthy adults in this study, with a replication sample of 104 (MS) and 39 (healthy adults). Participants reported their sociodemographic characteristics, and each was administered the oral Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test (CVLT-II), and the Brief Visuospatial Memory Test-Revised (BVMT-R). From the healthy control data, we developed regression-based norms incorporating race, age, education and sex. We then applied existing discrete norms and regression-based norms for the cognitive tests to the healthy controls, and generated z-scores which were compared using Spearman rank and concordance coefficients. We also used receiver operating characteristic (ROC) curves to compare the ability of each set of norms to discriminate between participants with and without MS. Within the MS samples we compared the ability of each set of norms to discriminate between differing levels of disability and employment status using relative efficiency.Results: When we applied the published regression norms to our healthy sample, impairment classification rates often differed substantially from expectations (7%), even when the norms were derived from a Canadian (Ontario) population. Most, but not all of the Spearman correlations between z-scores based on different existing published norms for the same cognitive test exceeded 0.90. However, concordance coefficients were often lower. All of the norms for the SDMT reliably discriminated between the MS and healthy control groups. In contrast, none of the norms for the CVLT-II or BVMT-R discriminated between the MS and healthy control groups. Within the MS population, the norms varied in their ability to discriminate between disability levels or employment status; locally developed norms for the SDMT and CVLT-II had the highest relative efficiency.Conclusion: Our findings emphasize the value of local norms when interpreting the results of cognitive tests and demonstrate the need to consider and assess the performance of regression-based norms developed in other populations when applying them to local populations, even when they are from the same country. Our findings also strongly suggest that the development of regression-based norms should involve larger, more diverse samples to ensure broad generalizability.

scholarly journals Correlation Between Disability Measure and Black Hole (T1 Hypointense Lesion) Lesion Load in Brain Magnetic Resonance Imaging (MRI) of Patients With Multiple Sclerosis (MS): Protocol for a Systematic Review and Meta-analysis

2021 ◽  
Author(s):  
Amir Valizadeh ◽  
Elham Barati ◽  
Mohammad Ali Sahraian ◽  
Mohammad Reza Fattahi ◽  
Mana Moassefi
Keyword(s):  
Multiple Sclerosis ◽  
Meta Analysis ◽  
Rank Correlation ◽  
Brain Magnetic Resonance Imaging ◽  
Lesion Volume ◽  
Spearman’S Rank Correlation ◽  
Spearman’S Rank Correlation Coefficient ◽  
Disability Status ◽  
Formation And Evolution ◽  
Magnetic Resonance Imaging Mri

Abstract Introduction: As the role of neurodegeneration in the pathophysiology of multiple sclerosis (MS) has become more prominent, the formation and evolution of chronic or persistent T1-hypointense lesions (Black Holes) have been used as markers of axonal loss and neuronal destruction to measure disease activity. However, findings regarding this subject are controversial. In this study we aim to clarify the level of importance of T1 hypointense lesions for estimating the prognosis of patients.Methods: We will search MEDLINE (through PubMed), Embase and Web of Science for relevant studies. We will extract the Spearman's rank correlation coefficient (SRCC) between the T1 hypointense lesion volume and Extended Disability Status Scale (EDSS) in participants. All included studies will be evaluated for the risk of bias. We will also perform a meta-analysis on the data. The risk of publication bias will be evaluated using Funnel plots. Finally, we will assess the confidence in cumulative evidence using an adapted version of GRADE.

scholarly journals Structural and functional connectomes in people with multiple sclerosis

2020 ◽  
Author(s):  
Ceren Tozlu ◽  
Keith Jamison ◽  
Susan Gauthier ◽  
Amy Kuceyeski
Keyword(s):  
Multiple Sclerosis ◽  
Functional Mri ◽  
Imaging Modality ◽  
Structural Connectivity ◽  
Receiver Operating Curve ◽  
Ensemble Prediction ◽  
P Value ◽  
Lesion Volume ◽  
Healthy Controls ◽  
Functional Connectome

One of the challenges in multiple sclerosis is that lesion volume does not correlate with symptom severity. Advanced techniques such as diffusion and functional MRI allow imaging of the brain's connectivity networks, which may provide better insight as to brain-behavior relationships in impairment and compensation in multiple sclerosis. We aim to build machine learning models based on structural and functional connectomes to classify a) healthy controls versus people with multiple sclerosis and b) impaired versus not impaired people with multiple sclerosis. We also aim to identify the most important imaging modality for both classification tasks, and, finally, to investigate which brain regions' connectome measures contribute most to the classification. Fifteen healthy controls (age=43.6 ± 8.6, 53% female) and 76 people with multiple sclerosis (age: 45.2 ± 11.4 years, 65% female, disease duration: 12.2 ± 7.2 years) were included. Twenty-three people with multiple sclerosis were considered impaired, with an Expanded Disability Status Scale of 2 or higher. Subjects underwent MRI scans that included anatomical, diffusion and resting-state functional MRI. Random Forest models were constructed using structural and static/dynamic functional connectome measures independently; single modality models were then combined for an ensemble prediction. The accuracy of the models was assessed by the area under the receiver operating curve. Models that included structural connectomes significantly outperformed others when classifying healthy controls and people with multiple sclerosis, having a median accuracy of 0.86 (p-value<0.05, corrected). Models that included dynamic functional connectome metrics significantly outperformed others when distinguishing people with multiple sclerosis by impairment level, having a median accuracy of 0.63 (p-value<0.05, corrected). Structural connectivity between subcortical, somatomotor, and visual networks was most damaged by multiple sclerosis. For the classification of patients with multiple sclerosis into impairment severity groups, the most discriminatory metric was dwell time in a dynamic functional connectome state characterized by strong connectivity between and among somatomotor and visual networks. These results suggest that damage to the structural connectome, particularly in the subcortical, visual, and somatomotor networks, is a hallmark of multiple sclerosis, and, furthermore, that increased functional coordination between these same regions may be related to severity of motor disability in multiple sclerosis. The use of multi-modal connectome imaging has the potential to shed light on mechanisms of disease and compensation in multiple sclerosis, thus enabling more accurate prognoses and possibly the development of novel therapeutics.

scholarly journals Dissociable cognitive patterns related to depression and anxiety in multiple sclerosis

2019 ◽  
Vol 26 (10) ◽  
pp. 1247-1255 ◽  
Author(s):  
Victoria M Leavitt ◽  
Rachel Brandstadter ◽  
Michelle Fabian ◽  
Ilana Katz Sand ◽  
Sylvia Klineova ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Sex Education ◽  
Processing Speed ◽  
Anxiety And Depression ◽  
Lesion Volume ◽  
Depression And Anxiety ◽  
Nonverbal Memory ◽  
Cognitive Correlates ◽  
Partial Correlations ◽  
Mood And Cognition

Background: Individuals with multiple sclerosis (MS) frequently present with depression and anxiety, as well as cognitive impairment, challenging clinicians to disentangle interrelationships among these symptoms. Objective: To identify cognitive functions associated with anxiety and depression in MS. Methods: Mood and cognition were measured in 185 recently diagnosed patients (Reserve Against Disability in Early Multiple Sclerosis (RADIEMS) cohort), and an independent validation sample (MEM CONNECT cohort, n = 70). Partial correlations evaluated relationships of cognition to anxiety and depression controlling for age, sex, education, and premorbid verbal intelligence. Results: In RADIEMS cohort, lower anxiety was associated with better nonverbal memory ( rp = –0.220, p = 0.003) and lower depression to better attention/processing speed ( rp = –0.241, p = 0.001). Consistently, in MEM CONNECT cohort, lower anxiety was associated with better nonverbal memory ( rp = –0.271, p = 0.028) and lower depression to better attention/processing speed ( rp = –0.367, p = 0.002). Relationships were unchanged after controlling for T2 lesion volume and fatigue. Conclusion: Consistent mood–cognition relationships were identified in two independent cohorts of MS patients, suggesting that cognitive correlates of anxiety and depression are separable. This dissociation may support more precise models to inform treatment development. Treatment of mood symptoms may mitigate effects on cognition and/or treatment of cognition may mitigate effects on mood.

scholarly journals B-12 Cognitive Resilience in MS: Associations with Lesion Volume, Pain, and Smoking Status

2019 ◽  
Vol 34 (6) ◽  
pp. 956-956
Author(s):  
J Randolph ◽  
J Randolph ◽  
H Wishart
Keyword(s):  
Smoking Status ◽  
Lesion Volume ◽  
Healthy Controls ◽  
Mild Depression ◽  
Complete Understanding ◽  
Age And Gender ◽  
Cognitive Difficulties ◽  
And Gender ◽  
Overall Functioning ◽  
Subjective Cognitive Complaints

Abstract Objective Cognitive dysfunction is common in people with MS (pwMS), but relatively little is known about those with no objective or subjective impairment. We sought to further examine a previously characterized cognitively resilient group of pwMS (MS-RES)—individuals without cognitive impairment, without subjective cognitive complaints, and without informant-reported cognitive difficulties—and considered neuroimaging, pain-related, and smoking correlates in this group. Method We derived two groups of pwMS: cognitively resilient (MS-RES; N = 15) and other MS (N = 85). MS groups showed equivalent education, gender, symptom and diagnosis duration, MS subtype, EDSS rating, and reported hours of sleep, and endorsed no more than mild depression. Both MS groups were compared to age- and gender-matched healthy controls (N = 31) on appropriate variables, and MS groups were compared on lesion volume, pain, and smoking variables. Results Despite showing intact subjective and objective cognition, the MS-RES group had lesion volume comparable to other MS participants. The MS-RES group also reported less of an impact of pain on overall functioning, recreational activities, and life enjoyment compared to other MS participants (p < .05), and were comparable to healthy controls. There was a trend toward MS-RES participants being less likely to be current smokers than others with MS (p = .09), and MS-RES and healthy controls showed comparable smoking status. Conclusions We found that cognitively resilient pwMS have unique clinical features that differentiate them from others with MS despite similar lesion volumes. A more complete understanding of cognitively resilient pwMS may inform interventions that promote MS symptom management and general resilience.

Deep gray matter T2 hypointensity is present in patients with clinically isolated syndromes suggestive of multiple sclerosis

2009 ◽  
Vol 16 (1) ◽  
pp. 39-44 ◽  
Author(s):  
Antonia Ceccarelli ◽  
Maria A Rocca ◽  
Mohit Neema ◽  
Vittorio Martinelli ◽  
Ashish Arora ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Caudate Nucleus ◽  
Gray Matter ◽  
Lesion Volume ◽  
Clinically Isolated Syndromes ◽  
Increased Risk ◽  
Left Caudate ◽  
Magnetic Resonance Imaging Mri ◽  
Putative Marker ◽  
In Cis

Gray matter (GM) magnetic resonance imaging (MRI) T2 hypointensity, a putative marker of iron deposition, is a frequent finding in patients with clinically definite (CD) multiple sclerosis (MS). The objective of this study was to assess: (a) how early deep GM T2 hypointensity occurs in MS, by studying patients with clinically isolated syndromes (CIS) suggestive of MS, and (b) whether they contribute to predict subsequent evolution to CDMS. Dual-echo scans using two different acquisition protocols were acquired from 47 CIS patients and 13 healthy controls (HC). Normalized T2-intensity of the basal ganglia and thalamus was quantified. Patients were assessed clinically at the time of MRI acquisition and after three years. During the observation period, 18 patients (38%) evolved to CDMS. At the baseline, only the GM T2-intensity of the left caudate nucleus was significantly reduced in CIS patients in comparison with the HC (p = 0.04). At the baseline, the T2 intensity of the left caudate nucleus was significantly lower (p = 0.01) in CIS patients with disease dissemination in space (DIS), but not in those without DIS, compared to the HC. The baseline T2 lesion volume, but not GM T2 hypointensity, was associated with evolution to CDMS (hazard ratio = 1.60, 95% confidence interval (CI) = 1.05—2.42; p = 0.02). In CIS patients, deep GM is not spared, suggesting that iron-related changes and neurodegeneration occurs early. The magnitude of such damage is only minor and not associated with an increased risk of evolution to CDMS.

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