Multiple Sclerosis (MS) is a chronic autoimmune disease where lymphocytes inflict damage to the axons and myelin sheaths of the central nervous system. Persons with multiple sclerosis (pwMS) were long advised to avoid physical activity but the benefits of exercise to improve cardiovascular and cognitive functions in pwMS have become important aspects of standardized rehabilitation programs. Recent findings show that the achieved adaptations through exercise are associated with the intensity dependent lactate increases during exercise. This dose-response relationship between the mode and the exercise intensity implicates the relevance of the exercise protocol as higher exercise intensities seem to facilitate greater benefits, also in pwMS.

This pilot study evaluates the influences of acute bout of moderate physical exercise (cycling) and relaxation on cognitive functions at three time points.

Primary outcomes are the differences (at timepoint t2) of cognitive functions assessed via the Symbol Digit Modalities Test (SDMT) and the Brief Visuospatial Memory Test Revised (BVMT-R) T1-3 of the BICAMS battery.

Results should into a randomised controlled Trial that investigates the specific influences of a three-week training intervention on Brain-derived neurotrophic factors (BDNF), Insulin Growth Factor-1 (IGF-1) and Vascular Endothelial Growth Factor (VEGF) as central neurobiological parameters of neuroplasticity, cardiorespiratory Fitness and cognitive functions.

Objectives To determine responses of an acute moderate exercise bout on cognitive functions in pwMS.

Hypothesis

• Comparisons of different Training modes: exercise (overland cycling) versus relaxation
• Improvements of cognitive functionning (Memory, processing Speed) on the Symbol Digit Modalities Test (SDMT) and the Brief Visuospatial Memory Test Revised (BVMT-R) T1-3
• Correlations between the intensity-dependent lactate increases and cognitive functions

Experimental design Two-pronged, case controlled study. Randomization of 20 MS patients into a Group "Exercise" (n=10) - that perform 30 minutes cycling on an Ergometer - or "Relaxation (n=10) that perform relaxation in a comfortable and quiet environment. Both groups crossover at t2 into the respective Group. The study is set into the normal rehabilitation program and participants are given physician clearance, are informed about the study and give their written consent before the study starts.

Cognitive assessment is performed with the Symbol Digit Modalities Test (SDMT) and the Brief Visuospatial Memory Test Revised (BVMT-R) T1-3.

SDMT tests information of processing speed. The test consists of single digits paired with abstract symbols. Rows of the nine symbols are arranged pseudo-randomly. The participant must say the number that corresponds with each symbol. The SDMT can be completed within 5 min, including instructions, practice and testing. The good psychometric properties of the SDMT are well described.

BVMT-R T1-3 requires the the participant to inspect a 2 × 3 stimulus array of abstract geometric figures. There are three learning trials of 10 s. The array is removed and the patient is required to draw the array from memory, with the correct shapes in the correct position. The psychometric properties of the BVMT-R T1-3 are good. Cognitive functions are assessed at time points t1 and t2 after Exercise / Relaxation.

At baseline participants perform a progressive cardiopulmonary exercise test (CPET) on a cycle ergometer (Ergoline 800, Germany). Cardiopulmonary fitness level was monitored by direct and continuous measurements (breath by breath) of maximum oxygen consumption (VO2peak) by ergospirometer (PanGas, CPX, Germany).

The exercise protocol consisted of (a) first 3 minutes at rest (no pedalling) on the cycle ergometer; (b) 3 minutes of unloaded pedalling as a warm up; (c) testing phase until the participant reached a symptom limited maximum. Workload was continuously ramp type increased by 5-10 Watts every minute to ensure 8-12 minutes of testing; (d) the final 3 minutes were unloaded pedalling to cool down. Heart rate (Polar Electro, Kempele, Finland) and blood pressure (Riva Rocci) were monitored for the last 10 seconds every 2 minutes during the test. The 10-point BORG scale therapy short form assessed the rate of perceived exertion (RPE) at phases (c) and (d). Peak oxygen consumption (VO2peak) was defined as the highest VO2 value when the following criteria were attained: respiratory equivalent ratio (RER) > 1.10; peak heart rate (HRpeak) within 10 min-1 of age predicted maximum and rating of exertion (RPE > 8.5).

The exercise bout consists of 30 minutes physiologically defined heart rate controlled cycling at 50-60 rounds per minutes (rpm) at the lactate threshold (equal to 75% of HRpeak or 60% VO2max).

Relaxation consists of 30 minutes resting in a comfortable and quiet surrounding. Exercise and Relaxation are performed at timepoints t1 and t2.

Inclusion Criteria:

• Expanded Disability status scale (EDSS) score of 1.5 - 6.0

Exclusion Criteria:

• Persisted infections, acute psychotic disorders, cardiovascular and pulmonal diseases, neuropsychological disorders that serverly impact the assessment or were psychotropic medication within the last six week.

Persons with multiple sclerosis holding an score of 1.5-6.0 on the Expanded Disability Staus Ccale (EDSS)