Progressive Aerobic Exercise May Help Improve Cognitively Impaired Patients With MS

December 11, 2020
Victoria Johnson
Victoria Johnson

Victoria Johnson, Assistant Editor for NeurologyLive, joined the MJH Life Sciences team in October 2020. Follow her on Twitter @VictoriaJNeuro or email her at

No cognitive improvements were observed for exercise versus waitlist groups of cognitively normal patients with MS.

A recent randomized controlled trial (RCT) investigated progressive aerobic exercise (PAE) in patients with multiple sclerosis (MS) and found that no effect on any cognitive domain was observed in patients overall after 24 weeks of supervised PAE, but a potential clinically relevant improvement in processing speed was seen in cognitively impaired patients.

No changes in Brief Repeatable Battery of Neuropsychological (BRB-N) test scores were seen in either the “exercise” or “waitlist” groups after PAE. When comparing cognitively impaired patients (43% of all patients, n = 37) between the 2 groups, there was a potential clinically relevant improvement in the symbol digit modalities test (SDMT).

Principal author Martin Langeskov-Christensen, PhD, researcher, Aarhus University, and colleagues wrote that “this is the first study to investigate cognitive performance outcomes in patients with MS in a longitudinal RCT following 24 weeks of supervised high-intensity PAE intervention... the potential effects of PAE were analyzed in both the total group and in the subgroup showing mild to moderate cognitive impairment, using a validated battery of neuropsychological tests.”

A total of 86 patients enrolled in the study and were randomized to either the exercise group (n = 43) or the waitlist control group (n = 43). Relapsing-remitting MS (RRMS) was the most common disease type, with 75 patients (87.2%) with enrolled. Based on a deviation in Z-scores from published reference BRB-N test scores, 37 patients (43%) were classified as cognitively impaired, 22 in the PAE group and 15 in the waitlist group. The exercise group underwent 24 weeks of supervised PAE followed by self-guided physical activity. The waitlist group underwent 24 weeks of their habitual lifestyles, followed by supervised PAE.

READ MORE: Aerobic Exercise Shows Positive Effect in Multiple Sclerosis

Cardiovascular fitness (VO2-max) increased between groups by 3.5 mL O2/min/kg (95% CI; 2.0–5.1; P <.01) in the exercise group vs the waitlist group. Around half of the overall planned exercise sessions were completed: 44.8 (standard deviation [SD], 2.6) of the planned 93.3 (SD, 5.4) sessions. In the exercise group, 12 patients were unable to adhere to the highest prescribed intensity (90% to 95% of max heart rate [HRmax]) of the last 8 weeks of PAE, and the mean intensity of these 12 patients was 87.8% HRmax

After 24 weeks, 13 patients (15.1%) had dropped out of the study, 7 from the PAE group and 6 from the waitlist. There were 9 (25.6%) additional dropouts from 24 to 48 weeks. The PAE intervention was well-tolerated and no serious adverse events occurred. After 48 weeks, the improvements in cardiovascular fitness seen in the exercise group disappeared (post-24 weeks of self-guided physical activity following the supervised PAE).

No cognitive improvement changes were observed between the groups after 24 weeks, but improvements in Z-scores were seen after 48 weeks in the initial exercise group. Long-term retrieval improved by 5.3 (95% CI. 2.0–8.6; P <.01), consistent long-term retrieval improved by 5.6 (95% CI. 1.1–10.1; P =.01), delayed recall in the selective reminding test (SRT) improved by 0.6 (95% CI. 0.1–1.1; P =.02), and verbal domain scores in the SRT improved by 0.4 (95% CI. 0.1–0.6; P <.01). Total BRB-N Z-scores improved by 0.2 (95% CI. 0.0–0.4; P =.02). The major depression inventory score increased by 2.4 (95% CI. 0.5–4.2; P =.01) as an indicator of worsened mood. 

Improvements at the 24- and 48-week mark were seen in the cognitively impaired subgroup of the exercise group (n = 22). Symbol digital modalities test (SDMT) scores, indicative of processing speed, increased by 4.9 (95% CI. 1.3–11.1; P <.01). Long-term retrieval improved by 6.8 (95% CI. 3.0–10.6; P <.01), consistent long-term retrieval improved by 7.4 (95% CI. 0.9–13.8; P =.03), delayed recall in the SRT improved by 1.2 (95% CI. 0.2–2.2; P =.02), and verbal domain scores in the SRT improved by 0.5 (95% CI. 0.2–0.9; P <.01).

“These results suggest no direct effect of PAE on cognitive performance in a representative group of patients with MS, whereas a potential clinical relevant improvement in processing speed was observed in a subgroup comprising cognitively impaired patients with MS... further adequately powered long-term and large-scale exercise studies, including well-defined cognitively impaired patients with MS and a validated battery of neuropsychological tests are warranted, since treatments specific for cognitive impairment in MS are highly needed,” Langeskov-Christensen and colleagues concluded.

Langeskov-Christensen M, Hvid LG, Jensen HB, et al. Efficacy of high-intensity aerobic exercise on cognitive performance in people with multiple sclerosis: A randomized controlled trial. Mult Scler. Published online November 24, 2020. doi:10.1177/1352458520973619