Effects of walking exercise training on learning and memory and hippocampal neuroimaging outcomes in MS: A targeted, pilot randomized controlled trial.

PURPOSE: The current pilot study involved a single-blind, randomized controlled trial (RCT) on the effects of treadmill walking exercise training compared with an active control condition on learning and memory (L/M) and hippocampal neuroimaging outcomes in 11 fully-ambulatory persons with multiple sclerosis (MS) who demonstrated impairments in new learning. METHODS: The study protocol is registered at clinicaltrials.gov: NCT03319771 (February 2018). Eleven fully-ambulatory persons with MS-related impairments in new learning were randomly assigned into either 12-weeks of supervised, treadmill walking exercise training or 12-weeks of low-intensity resistive exercise (active control condition). Participants underwent neuropsychological tests of L/M and hippocampal neuroimaging before and after the 12-week study period; outcomes were administered by treatment-blinded assessors. RESULTS: There were moderate-to-large intervention effects on measures of verbal L/M (ηp2 = 0.11, d = 0.63, 95% CI: -0.61, 1.83), whereby those in the intervention condition demonstrated improvement in California Verbal Learning Test-II (CVLT-II) scores compared with the control condition. There were smaller effects on a composite L/M measure (ηp2 = 0.02, d = 0.28, 95% CI: -0.93, 1.46). There were large intervention effects on normalized hippocampal volume (ηp2 = 0.36, d = 1.13, 95% CI: 0.09, 2.82), whereby hippocampal volume was preserved in the intervention condition, compared with hippocampal atrophy in the control condition. By comparison, there were no intervention effects on hippocampal resting-state functional connectivity. CONCLUSIONS: Collectively, this study provides initial proof-of-concept data for further examining treadmill walking exercise training as a possible behavioral approach for managing L/M impairment and preserving hippocampal volume as common and debilitating manifestations of MS.

Relationships between cognitive function, seizure control, and self-reported leisure-time exercise in epilepsy.

Exercise may be a strategy for improvement of cognitive deficits commonly present in people with idiopathic generalized epilepsies (IGE). We investigated the relationship between cognition and level of physical exercise in leisure (PEL) in people with IGE who have been seizurefree for at least 6 months (IGE-) as compared to those who have not been seizurefree (IGE+) and healthy controls (HCs). We hypothesized that higher level of physical exercise is associated with better cognitive functioning in patients with IGE and HCs, and that seizure control affects both PEL levels and cognitive functioning in patients with IGE. We recruited 75 participants aged 18-65: 31 people with IGE (17 IGE-, 14 IGE+) and 44 HCs. Participants completed assessments of quality of life (SF-36), physical activity levels (Baecke questionnaire and International Physical Activity Questionnaire (IPAQ)) and cognition (Montreal Cognitive Assessment (MoCA), Hopkins Verbal Learning Test - Revised (HVLT), and flanker task). Group differences (HCs vs. IGE; HCs vs. IGE+ vs. IGE-) were assessed. Pearson correlations examined linear relationships between PEL and cognitive performance. Groups were similar in age and sex. Compared to HCs, patients with IGE had higher body mass index, fewer years of education, and consistently scored worse on all measures except flanker task accuracy on incongruent trials. When examining IGE- and IGE+ subgroups, compared to HCs, both had higher body mass index, and fewer years of education. Healthy controls scored significantly better than one or both of the IGE groups on SF-36 scores, PEL levels, IPAQ activity level, MoCA scores, HVLT learning and long-delay free-recall scores, and flanker task accuracy on congruent trials. Among patients with IGE, there were no significant differences between age of epilepsy onset, duration of epilepsy, number of anti-seizure drugs (ASDs) currently being used, or the group distribution of type of IGE. In the combined sample (IGE+, IGE- and HCs), PEL positively correlated with MoCA scores (Pearson's r = 0.238; p = 0.0397) and with flanker task accuracy on congruent trials (Pearson's r = 0.295; p = 0.0132). Overall, patients with IGE performed worse than HCs on cognitive and physical activity measures, but the cognitive impairments were more pronounced for IGE+, while physical exercise levels were less for patients with IGE regardless of seizure control. While positive relationships between leisure-time PEL and cognitive performance are promising, further investigations into how exercise levels interact with cognitive functioning in epilepsy are needed.

Protocol for a systematically-developed, phase I/II, single-blind randomized controlled trial of treadmill walking exercise training effects on cognition and brain function in persons with multiple sclerosis.

Slowed cognitive processing speed (CPS) is a common and debilitating consequence of multiple sclerosis (MS) that is notoriously difficult to treat. As such, we undertook a systematic line of research that indicated that supervised, progressive treadmill walking exercise (TMWX) training might improve CPS and brain functioning among fully-ambulatory persons with MS. The current study will be the first adequately-powered, single-blind randomized controlled trial (RCT) that examines the efficacy of 12-weeks of TMWX training compared with an active control condition on CPS, thalamocortical brain connectivity (based on resting-state fMRI), and exploratory functional outcomes in 88 fully-ambulatory persons with MS who present with slowed CPS. The intervention condition involves supervised, progressive TMWX training 3 times/week over 12-weeks; this initially involves 15-min of light-to-moderate intensity TMWX that progresses up to 40-min of vigorous intensity TMWX. The active control condition involves supervised, minimal intensity, stretching-and-resistance exercise that will be delivered on the same frequency as the intervention condition. The primary study outcomes involve Symbol Digit Modalities Test performance (i.e., CPS) and fMRI-based measures of thalamocortical resting-state functional connectivity. Exploratory study outcomes involve measures of community participation, activities of daily living, quality of life, and functional mobility. All study outcomes will be administered before and after the 12-week study period by treatment-blinded assessors. If successful, the current study will provide the first Class I evidence for the effects of TMWX training as an approach for improving CPS and its neural correlate, and possibly mitigating the impact of slowed CPS on functional outcomes in MS.