Longitudinal associations between MRI and cognitive changes in very early MS

Nourbakhsh, Bardia; Nunan-Saah, Julia; Maghzi, Amir Hadi; Julián, Laura; Spain, Rebecca; Jin, Chengshi; Lazar, Ann; Pelletier, Daniel; Waubant, Emmanuelle

doi:10.1016/j.msard.2015.10.010

Cited by 31 publications

(23 citation statements)

References 30 publications

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“…This contrasts findings in MS cohorts with a wider spectrum of disability in which a relation of SDMT to whole brain measures (brain volume, T2 lesion volume) was evident (63), while evidence of such relationship in patients with early relapsing-remitting MS or CIS is sparse (63, 64). Consistent with our findings, more recent studies in early RRMS or CIS cohorts (32, 65, 66) were unable to confirm correlations of SDMT performance with volumetric brain measures while Bisecco et al have reported on thalamic atrophy as an independent and additional contributor to SDMT variance in a cross-sectional analysis controlled for sex and age of 125 RRMS patients (mean age 37 years, median EDSS 2) (67). However, they used a different analytic approach (voxel-based morphometry analysis) and the MS group differed more significantly in several compartmental volumes (NBV, NGMV and NWMV) from the HC group, suggesting higher overall atrophy compared to our CIS and RRMS groups.…”

Section: Discussionsupporting

confidence: 72%

“…Whilst the existing body of literature generally confirms such association in MS cohorts with significant disability, evidence on functional correlates of brain atrophy in CIS and early RRMS patients is less compelling (31, 32). The scope of this study was therefore to explore the relation of imaging markers of disease severity with the above-mentioned hallmark parameters of functional decline in a cohort of mildly disabled CIS and RRMS patients (EDSS ≤3).…”

Section: Introductionmentioning

confidence: 99%

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MRI Markers and Functional Performance in Patients With CIS and MS: A Cross-Sectional Study

et al. 2018

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Introduction: Brain atrophy is a widely accepted marker of disease severity with association to clinical disability in multiple sclerosis (MS). It is unclear to which extent this association reflects common age effects on both atrophy and function.Objective: To explore how functional performance in gait, upper extremities and cognition is associated with brain atrophy in patients with Clinically Isolated Syndrome (CIS) and relapsing-remitting MS (RRMS), controlling for effects of age and sex.Methods: In 27 patients with CIS, 59 with RRMS (EDSS ≤3) and 63 healthy controls (HC), 3T MRI were analyzed for T2 lesion count (T2C), volume (T2V) and brain volumes [normalized brain volume (NBV), gray matter volume (NGMV), white matter volume (NWMV), thalamic volume (NThalV)]. Functional performance was measured with short maximum walking speed (SMSW speed), 9-hole peg test (9HPT) and symbol digit modalities test (SDMT). Linear regression models were created for functional variables with stepwise inclusion of age, sex and MR imaging markers.Results: CIS differed from HC only in T2C and T2V. RRMS differed from HC in NBV, NGMV and NThalV, T2C and T2V, but not in NWMV. A strong association with age was seen in HC, CIS and RRMS groups for NBV (r = −0.5 to −0.6) and NGMV (r = −0.6 to −0.8). Associations with age were seen in HC and RRMS but not CIS for NThalV (r = −0.3; r = −0.5), T2C (rs = 0.3; rs = 0.2) and T2V (rs = 0.3; rs = 0.3). No effect of age was seen on NWMV. Correlations of functional performance with age in RRMS were seen for SMSW speed, 9HPTand SDMT (r = −0.27 to −0.46). Regression analyses yielded significant models only in the RRMS group for 9HPT, SMSW speed and EDSS. These included NBV, NGMV, NThalV, NWMV, logT2V, age and sex as predictors. NThalV was the only MRI variable predicting a functional measure (9HPTr) with a higher standardized beta than age and sex (R2 = 0.36, p < 1e-04).Conclusion: Thalamic atrophy was a stronger predictor of hand function (9HPT) in RRMS, than age and sex. This underlines the clinical relevance of thalamic atrophy and the relevance of hand function as a clinical marker even in mildly disabled patients.

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Section: Discussionsupporting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

MRI Markers and Functional Performance in Patients With CIS and MS: A Cross-Sectional Study

et al. 2018

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“…In the longitudinal analysis of the present study, the patients showed stabilization or improvement in VEM performance, corroborating the findings of some longitudinal studies 17,18,19,20,21,22,23,24 , yet contrasting with others showing decline 4,6,25,26 in this domain. These incongruent findings have been reported in recently-published systematic reviews on the subject 1,2,3 .…”

Section: Discussionsupporting

confidence: 91%

Longitudinal analysis of verbal episodic memory in patients with relapsing-remitting multiple sclerosis

Boa

Rimkus

Campanholo

et al. 2018

Arq. Neuro-Psiquiatr.

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Objective: A 4.5-year follow-up study was conducted to characterize baseline verbal episodic memory (VEM) and its behavior and to assess the effects of relapsing-remitting multiple sclerosis (RRMS) on this domain. Methods: Twenty-nine patients with RRMS underwent two neuropsychological assessments performed an average of 4.5 years apart. Twenty-six control participants underwent a single neuropsychological assessment. A significance level of p < 0.005 was adopted to denote a significant difference between the groups on the Mann Whitney and Wilcoxon paired statistical analyses. Results: No statistical difference was found in the results of the VEM tests between the first and second neuropsychological assessments of the patients. However, a statistical difference was evident between the patient and control groups in the results of the VEM tests. Conclusion: The patient group showed changes in the VEM relative to the control group. After approximately 4.5 years of disease, the patient performance on the VEM stabilized or improved.Keywords: multiple sclerosis; cognition; longitudinal studies. RESUMOObjetivo: Neste estudo, propomos a caracterização da Memória Episódica Verbal (MEV) basal e o seu comportamento após o período de 4,5 anos de doença, a fim de avaliar o efeito da EMRR neste domínio. Métodos: Vinte e nove pacientes com EMRR foram submetidos a duas avaliações neuropsicológicas realizadas entre um intervalo de tempo médio de 4,5 anos. Vinte e seis controles foram submetidos à avaliação neuropsicológica única. Considerou-se nível de significância p <0,005 para delinear diferença significante entre os grupos nas análises estatísticas Mann Whitney e Wilcoxon pareado. Resultados: Não houve diferença estatística nos resultados dos testes de MEV entre a primeira e segunda avaliação neuropsicológica realizada pelos pacientes. Houve discrepância estatística nos resultados dos testes de MEV entre o grupo dos pacientes e controles. Conclusão: O grupo de pacientes apresentou alterações de MEV quando comparado aos controles. Após 4,5 anos aproximadamente os pacientes estabilizaram ou melhoraram seu desempenho em MEV.Palavras chave: esclerose múltipla; cognição; estudos longitudinais.Patients with multiple sclerosis (MS) clinically present with a myriad of neurologic symptoms, including cognitive decline, regarded as having the greatest impact on key aspects of their daily living, such as managing domestic tasks, participating in society and holding down a job 1 . According to reviews of the scientific literature, one third of MS patients with the relapsing-remitting (RRMS) clinical form show cognitive impairments that are often milder than that found in the progressive subtypes of the disease 2,3 . Cognitive impairments can vary, but an impact on episodic memory is evident in the early stages of the disease. A 10-year longitudinal study revealed that decline in information processing speed and verbal episodic memory (VEM) in early RRMS patients predicted progression to the secondary progressive MS clinical form....

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“…For example, in five cross‐sectional18, 23, 24, 25, 26 and two longitudinal studies,2, 38 which included between 43 and 81 patients in very early stages of MS, no significant associations between MRI lesion burden and cognitive measures were reported. Four of these studies also examined the relationships between global or regional brain atrophy and cognitive measures but found no associations 2, 24, 25, 26. Other studies did not find associations between MRI and cognitive measures presumably due to the small sample size and heterogeneity of studied cohorts 17, 19, 20, 21…”

Section: Discussionmentioning

confidence: 99%

Cognitive clinico‐radiological paradox in early stages of multiple sclerosis

Uher

Krásenský

Sobíšek

et al. 2017

Ann Clin Transl Neurol

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ObjectiveTo investigate whether the strength of the association between magnetic resonance imaging (MRI) metrics and cognitive outcomes differs between various multiple sclerosis subpopulations.MethodsA total of 1052 patients were included in this large cross‐sectional study. Brain MRI (T1 and T2 lesion volume and brain parenchymal fraction) and neuropsychological assessment (Brief International Cognitive Assessment for Multiple Sclerosis and Paced Auditory Serial Addition Test) were performed.ResultsWeak correlations between cognitive domains and MRI measures were observed in younger patients (age≤30 years; absolute Spearman's rho = 0.05–0.21), with short disease duration (<2 years; rho = 0.01–0.21), low Expanded Disability Status Scale [EDSS] (≤1.5; rho = 0.08–0.18), low T2 lesion volume (lowest quartile; <0.59 mL; rho = 0.01–0.20), and high brain parenchymal fraction (highest quartile; >86.66; rho = 0.01–0.16). Stronger correlations between cognitive domains and MRI measures were observed in older patients (age>50 years; rho = 0.24–0.50), with longer disease duration (>15 years; rho = 0.26–0.53), higher EDSS (≥5.0; rho = 0.23–0.39), greater T2 lesion volume (highest quartile; >5.33 mL; rho = 0.16–0.32), and lower brain parenchymal fraction (lowest quartile; <83.71; rho = 0.13–0.46). The majority of these observed results were confirmed by significant interactions (P ≤ 0.01) using continuous variables.InterpretationThe association between structural brain damage and functional cognitive impairment is substantially weaker in multiple sclerosis patients with a low disease burden. Therefore, disease stage should be taken into consideration when interpreting associations between structural and cognitive measures in clinical trials, research studies, and clinical practice.

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Longitudinal associations between MRI and cognitive changes in very early MS

Cited by 31 publications

References 30 publications

MRI Markers and Functional Performance in Patients With CIS and MS: A Cross-Sectional Study

MRI Markers and Functional Performance in Patients With CIS and MS: A Cross-Sectional Study

Longitudinal analysis of verbal episodic memory in patients with relapsing-remitting multiple sclerosis

Cognitive clinico‐radiological paradox in early stages of multiple sclerosis

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