Don't be Late! Postponing Cognitive Decline and Preventing Early Unemployment in People With Multiple Sclerosis

Quality of life assessed using the 36-item Short Form. Item-scores are summed and transformed into a total score that ranges 0-100. Higher score corresponds with better quality of life.

Information processing speed is assessed using the Symbol Digit Modalities Test (SMDT). The total responses made in 90 seconds is administered. Higher amount of correct responses equals better information processing speed.

Information processing speed is assessed using the Paced Auditory Serial Addition Test (PASAT). The total correct answers given, out of 60, is administered. Higher amount of correct responses equals better information processing speed.

Verbal fluency is assessed using the Dutch adaptation of the Controlled Oral Word Association Test; Dutch Letter Fluency Test. Total number of correct words will be administered. Higher score corresponds with better verbal fluency.

Spatial Processing is assessed using the Judgement of Line Orientation. Total correct responses, with maximum 30, will be administered. Higher score corresponds with better spatial processing.

New Learning and Memory is assessed using the California Verbal Learning Test, second edition (CVLT-II). Direct recall on the CVLT-II will be administered using number of correctly remembered items over learning trials 1-5. Delayed recall on CVLT-II will be administered using number of correctly remembered items 20 minutes after learning trail 5. Maximum scores for direct recall, delayed recall, and recognition are set at 80, 16, and 44, respectively. Higher score equals better verbal learning and memory.

New Learning and Memory is assessed using the Brief Visuospatial Memory Test-Revised (BVMT-R). Direct recall on BVMT-R will be administered using number of correctly remembered items over learning trials 1-3. Delayed recall on BVMT-R will be administered using number of correctly remembered items 25 minutes after learning trail 3. Maximum scores for direct recall, delayed recall, and recognition are set at 36, 12, and 12, respectively. Higher score equals better visual learning and memory.

Executive Function is assessed using the Delis-Kaplan Executive Function System. Total correct sorts will be administered, with a maximum of 16 sorts. A higher score suggests better executive functioning.

Self-Reported Cognitive Functioning is assessed using the Multiple Sclerosis Neuropsychological Screening Questionnaire. Maximum score of 70 can be reached, with a score of 27 or higher indicating presence of neuropsychological problems.

Work Participation and Productivity is assessed using the Work Productivity and Activity Impairment Questionnaire: General Health, which administers the effect of health-problems on ability to work. Scores are calculated as percentages, with higher numbers indicating greater impairment and less productivity.

Work Difficulties are assessed using the Multiple Sclerosis Work Difficulties Questionnaire. The questionnaire consists of 23 items, which can be grouped into three subscales: psychological/cognitive barriers, physical barriers, and external barriers. The maximum score of each subscale is 100, with higher scores indicating higher perceived difficulties. Total score consists of an average of the three subscale scores.

Capability to carry out Work Activities is assessed using the Capability Set for Work Questionnaire. This questionnaire evaluates for seven valued work aspects whether, A) it is important to the worker, B) their work offers sufficient opportunities to do it, and C) it can be achieved, on a 5-point Likert scale.

Quality of Working Life is assessed using the Quality of Working Life Questionnaire for Cancer Survivors. The questionnaire consists of five subscales: meaning of work, perception of the work situation, atmosphere in the work environment, understandings and recognition in the organisation, and problems due to health situation. The overall score and sum scores of the subscales are calculated with a standardised score 0-100. Higher score corresponds with better quality of working life.

Grey Matter Volume will be determined using FSL-SIENAX, after lesion filling on the 3DTI.

White Matter Volume will be determined using FSL-SIENAX, after lesion filling on the 3DTI.

Total Brain Volume will be determined using FSL-SIENAX, after lesion filling on the 3DTI.

Volumes of Deep Grey Matter Structures will be determined using FIRST.

Cortical Thickness will be determined using Freesurfer.

White Matter Integrity will be determined using Diffusion Tensor Imaging

Functional Connectivity will be determined using Resting-State fMRI

Regional Functional Activation will be determined using Task-Based fMRI

Fatigue will be assessed using the Checklist Individual Strength. The questionnaire consists of 20 items, scored on a 7-point Likert scale. Fatigue is a subscale of the questionnaire, and is scored by adding the scores of the items, where a higher score corresponds with more fatigue.

Mood and Anxiety will be assessed using the Hospital Anxiety and Depression Scale. The questionnaire consists of 14 items on a 4-point Likert scale. The range of scores is 0-21 where a higher score equals more complaints of anxiety and depression.

Resilience will be assessed using the Connor Davidson Resilience Scale. Total score ranges 0-100, with higher scores reflecting greater resilience.

Perceived Level of Stress will be assessed using the Perceived Stress Scale. Total score ranges 0-40, with higher scores indicating higher perceived stress.

Social Mindfulness will be assessed using the SoMi paradigm by van Doesum et al. (2013). Choices that are made are scores as mindful (1) or unmindful (0). Final score will be computed by averaging the scores over all decisions, resulting in a number between 0 (unmindful) and 1 (mindful).

Social Participation will be assessed using the PROMIS 'Ability to Participate in Social Roles and Activities' item bank. The questionnaire consists of eight items that can be scored on a 5-point Likert scale. Higher scores indicate better ability to participate in social roles and activities.

MS-related disability will be assessed using the Expanded Disability Status Scale. This scale ranges from 0.0 to 10.0, where a higher score indicates worse disability.

Balance will be assessed using the Mini-BESTest. The test contains 14 items where a total score of 28 points can be achieved, where a score <19 induces an increased risk of falling.

Walking Speed will be assessed using the Timed 25-Foot Walk.

Endurance will be assessed using the Shuttle Walk Test according to the protocol of Singh et al. (1992).

Grip Strength will be assessed using a JAMAR hand-held dynamometer.

Upper Limb Dexterity will be assessed using the 9-Hole Peg Test and the Purdue Pegboard Test.

Lost Productivity Costs will be assessed using the iMTA Productivity Cost Questionnaire. The questionnaire consists of three modules measuring absenteeism, presenteeism, and productivity loss from unpaid work.

Societal Costs will be assessed using the iMTA Medical Consumption Questionnaire.

Quality Adjusted Life Years will be assessed using the EuroQol five-dimensional Questionnaire. The questionnaire comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Higher scores indicate more problems considering the dimensions.