Microstructural changes precede depression in patients with relapsing-remitting Multiple Sclerosis.

BACKGROUND: Multiple Sclerosis lesions in the brain and spinal cord can lead to different symptoms, including cognitive and mood changes. In this study we explore the temporal relationship between early microstructural changes in subcortical volumes and cognitive and emotional function in a longitudinal cohort study of patients with relapsing-remitting Multiple Sclerosis. METHODS: In vivo imaging in forty-six patients with relapsing-remitting Multiple Sclerosis was performed annually over 3 years magnetic resonance imaging. Microstructural changes were estimated in subcortical structures using the free water fraction, a diffusion-based MRI metric. In parallel, patients were assessed with the Hospital Anxiety and Depression Scale amongst other tests. Predictive structural equation modeling was set up to further explore the relationship between imaging and the assessment scores. In a general linear model analysis, the cohort was split into patients with higher and lower depression scores. RESULTS: Nearly all subcortical diffusion microstructure estimates at the baseline visit correlate with the depression score at the 2 years follow-up. The predictive nature of baseline free water estimates and depression subscores after 2 years are confirmed in the predictive structural equation modeling analysis with the thalamus showing the greatest effect size. The general linear model analysis shows patterns of MRI free water differences in the thalamus and amygdala/hippocampus area between participants with high and low depression score. CONCLUSIONS: Our data suggests a relationship between higher levels of free-water in the subcortical structures in an early stage of Multiple Sclerosis and depression symptoms at a later stage of the disease.

Signals between the brain and spinal cord are disrupted in people with Multiple Sclerosis. For those with relapsing-remitting Multiple Sclerosis (RRMS), symptoms get periodically better and worse over time. We looked at whether changes in the brain of people with RRMS were associated with changes in their mood over time. People who had more changes in certain areas of the brain at the start of the study were more likely to have symptoms of depression later. This work suggests that early changes in the brain may be linked to increased symptoms of depression over time in people with RRMS. We believe this could be an opportunity to provide care to those suffering from RRMS to lessen the impact of severe depression symptoms before they arise.

Brief international cognitive assessment for MS (BICAMS) and global brain volumes in early stages of MS - A longitudinal correlation study.

BACKGROUND: Cognitive impairment is common in patients with multiple sclerosis, even in the early stages of the disease. The Brief International Cognitive Assessment for multiple sclerosis (BICAMS) is a short screening tool developed to assess cognitive function in everyday clinical practice. OBJECTIVE: To investigate associations between volumetric brain measures derived from a magnetic resonance imaging (MRI) examination and performance on BICAMS subtests in early stages of multiple sclerosis (MS). METHODS: BICAMS was used to assess cognitive function in 49 MS patients at baseline and after one and two years. The patients were separated into two groups (with or without cognitive impairment) based on their performances on BICAMSs subtests. MRI data were analysed by a software tool (MSMetrix), yielding normalized measures of global brain volumes and lesion volumes. Associations between cognitive tests and brain MRI measures were analysed by running correlation analyses, and differences between subgroups and changes over time with independent and paired samples tests, respectively. RESULTS: The strongest baseline correlations were found between the BICAMS subtests and normalized whole brain volume (NBV) and grey matter volume (NGV); processing speed r = 0.54/r = 0.48, verbal memory r = 0.49/ r = 0.42, visual memory r = 0.48 /r = 0.39. Only the verbal memory test had significant correlations with T2 and T1 lesion volumes (LV) at both time points; T2LV r = 0.39, T1LV r = 0.38. There were significant loss of grey matter and white matter volume overall (NGV p<0.001, NWV p = 0.003), as well as an increase in T1LV (p = 0.013). The longitudinally defined confirmed cognitively impaired (CCI) and preserved (CCP) patients showed significant group differences on all MRI volume measures at both time points, except for NWV. Only the CCI subgroup showed significant white matter atrophy (p = 0.006) and increase in T2LV (p = 0.029). CONCLUSIONS: The present study found strong correlations between whole brain and grey matter volumes and performance on the BICAMS subtests as well as significant changes in global volumes from baseline to follow-up with clear differences between patients defined as cognitively impaired and preserved at both baseline and follow-up.

A two-year longitudinal follow-up of cognitive performance assessed by BICAMS in newly diagnosed patients with MS.

BACKGROUND: Cognitive impairment is common in patients with multiple sclerosis (MS) and may occur at any stage and with any subtype of the disease. Screening and monitoring of cognitive function should therefore be implemented into everyday clinical neurology practice. The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) was developed for this purpose. Although several cross-sectional studies have validated BICAMS, longitudinal studies evaluating its use as part of a clinical follow-up routine are still lacking. OBJECTIVE: To investigate cognitive function and trajectories of change assessed by the BICAMS test battery in a cohort of newly diagnosed relapsing-remitting MS (RRMS) patients examined at baseline and after 12 and 24 months. METHODS: BICAMS was used to assess cognitive function in 58 RRMS patients, who also filled in the Hospital Anxiety and Depression Scale (HADS) and the Fatigue Scale for Motor and Cognitive Functions (FSMC), and underwent standard neurological evaluations at baseline and at the two follow-ups. RESULTS: A total of 27 patients (46.6%) were defined as cognitively impaired at baseline on at least one test, and 22 (37.9%) were defined as impaired at follow-up after 24 months. Throughout the study, 8 (13.8%) and 4 (6.9%) patients were consistently defined as impaired on two or three tests, respectively. The mean raw scores on two BICAMS subtests (SDMT and CVLT-II) improved significantly from baseline to the first follow-up, and then remained stable the next year, whereas the visual memory test (BVMT-R) were overall unchanged from baseline to the end of the study. The correlations between the scores on HADS, FSMC and the BICAMS subtests were non-significant at baseline, but weak to moderate negative correlations were found at the one- and two-year follow-ups. CONCLUSION: The patients showed improved test results from baseline to the first follow-up examination, indicating that an effect of previous practise should be taken into account when interpreting the results. With results showing both trajectories of stability and change, our study supported the validity of including BICAMS as part of a clinical follow-up routine of RRMS patients. Anxiety, depression, fatigue and cognition should always be assessed at the same time to reveal interaction effects that are expected to affect the daily-life functioning of at least some of the RRMS patients.

The Norwegian translation of the brief international cognitive assessment for multiple sclerosis (BICAMS).

BACKGROUND: Cognitive impairment is a common symptom in all stages of multiple sclerosis (MS), yet it is underreported and not routinely evaluated. The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) is a short and easily administered test battery for screening of cognitive impairment in MS that can be completed within 15 min and incorporated into routine clinical practice. The test battery consists of the oral version of the Symbols Digit Modalities Test (SDMT) and the initial learning trials of the California Verbal Learning Test 2nd edition (CVLT-II) and the Brief Visuospatial Memory Test Revised (BVMT-R). OBJECTIVE: To investigate if the Norwegian version of the BICAMS could identify cognitive impairment in early stages of MS and be used as part of routine follow-up procedures. METHODS: A total of 65 relapsing-remitting MS (RRMS) patients and 68 healthy controls were examined with the BICAMS test battery. A randomly selected subset of 29 controls were retested 1-4 weeks after baseline. All participants were screened for anxiety and depression using the Hospital Anxiety and Depression Scale (HADS). RESULTS: There were statistically significant differences between the patients with MS and the healthy controls on all three subtests, and the differences remained significant for the CVLT-II (p = 0.003) and BVMT-R (p = 0.011) after adjusting for education. There were no statistically significant correlations between BICAMS scores and anxiety and depression. SDMT and BVMT-R results in the control group at baseline and re-test were strongly correlated (r ≥ 0.70, p < 0.001), and CVLT-II achieved an adequate value of r = 0.60 (p = 0.001). On the SDMT, there was a statistically significant improvement between the two test-sessions. Cognitive impairment, defined as an abnormal test score on ≥1 subtest, was identified in 46.2% of the patient sample, whereas 15.4% were considered cognitively impaired on ≥2 subtests. CONCLUSION: This study supports that the Norwegian version of the BICAMS should be included as a screening procedure for cognitive impairment in Norwegian MS patients.