Cognitive impairment affects roughly 50% of people with multiple sclerosis (MS). There are
currently no satisfactory medical treatments for cognitive impairments related to MS and
alternative forms of treatment are needed. Exercise training can improve cognition in older
adults and people with mild cognitive impairments, including those with early Alzheimer's
disease. Therefore, the investigators plan to conduct the first definitive study that will
test the theory that moderately intense aerobic exercise can improve cognition in people with
MS-related impairment - specifically in information processing speed - more so than
non-aerobic stretching and toning (both forms of exercise will be performed 3 days per week
for 6 months).
Primary study hypothesis: The investigators hypothesize greater improvement in speed of
information processing from pre- to post-treatment in the aerobic exercise group compared to
the stretching and toning group (attention control).
Secondary study hypothesis: The investigators hypothesize greater improvement in other
cognitive domains and patient reported outcomes from pre- to post-testing in the aerobic
exercise group compared to the stretching and toning group (attention control).
The investigators plan to recruit 125 adults with MS who can walk without assistance and
without rest for at least 100 meters and have mild weaknesses in information processing
speed. The investigators will randomly assign 50% of participants to an aerobic exercise
program and 50% to a non-aerobic exercise program (stretching and toning). In order to
determine whether the intervention is successful, the investigators will compare cognitive
functioning in both exercise groups before the exercise-training program, at the end of the
6-month training program and three months after the end of the training program. If our study
findings support our hypotheses, this would be a relatively no-barriers treatment option to
further explore for other people with MS including people with greater and lesser baseline
- English as primary language.
- At least 9th grade education.
- Physician confirmed, clinically definite MS diagnosis as defined by the revised
- All MS subtypes will be included.
- MS diagnosis at least 6 months prior.
- Impaired speed of information processing and working memory based on either the
PASAT-3" or the SDMT (i.e. z <-1.5 controlling for age, education and sex).
- Physician clearance to engage in aerobic exercise training.
- Able to walk at least 100 meters without assistance (Expanded Disability Severity
Scale score equivalent 0-5.5).
- Currently exercising less than public health recommendations (engaging in less than 30
minutes of structured physical activity less than 3 times per week during the past 6
- Willingness not to undertake additional structured exercise or leisure time physical
activity during the 6-month trial.
- Willing and able to participate in either exercise training program 3 days per week
for 6 months at a YMCA in the Greater Seattle Area.
- Near visual acuity with correction 20/70 or worse.
- Contra-indications for exercise training based on American Heart Association
(AHA)/ACSM screening criteria using PAR-Q.
- Using any medication known to have adverse effects on motor or cognitive function,
including monoamine oxidase inhibitors, sympathomimetics, antipsychotic agents,
modafinil, oxybutynin, tricyclic antidepressants, cholinesterase inhibitors and
anticonvulsants other than gabapentin and pregabalin. The following are permitted if
the patient has been on a stable dose for at least 6 weeks: short acting
benzodiazepines (qhs administration only), anti-spasmodics, selective serotonin
reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors.
- Received steroids in last 30 days.
- Relapse in the last 90 days.
- Undergone neuropsychological testing within the past 6-months.
- Neurological/psychological disease other than MS that may impact cognitive status,
e.g. Alzheimer's disease, Parkinson's, stroke, TIA, Vascular Dementia, Huntington's,
traumatic brain injury or chronic CNS infection.
- Dementia based on a definition validated in people with MS using the MACFIMS (> 2 SD
below the mean on at least one memory test and > 2 SD below the mean on at least one
neuropsychological test in another domain).
- Prior history of diagnosis or treatment for serious mental illness
(obsessive-compulsive disorder, schizophrenia, other psychotic disorders, bipolar
- Diagnosis of major depressive disorder prior to the diagnosis of MS.
- History of significant developmental or learning disorder that may affect
participation and confound interpretation of study results.
- Current major depressive disorder.
- Current alcohol or other drug abuse as measured by the WHO Alcohol, Smoking and
Substance Involvement Screening Test (WHO ASSIST V3.0).