Rationale and methodology for examining the combination of aerobic exercise and cognitive rehabilitation on new learning and memory in persons with multiple sclerosis and mobility disability: Protocol for a randomized controlled trial

• Published in: Contemporary clinical trials 2024-09, Vol.144, p.107630, Article 107630
• Main Authors: Wender, Carly L.A., Arbelaez, Odalys, Tong, Tien T., Salter, Amber, Wylie, Glenn R., Motl, Robert W., Sandroff, Brian M., Chiaravalloti, Nancy D.
• Format: Article
• Language: English
• Subjects: Adult; Cardiorespiratory Fitness - physiology; Cognitive rehabilitation; Cognitive Training; Exercise; Exercise - physiology; Exercise Therapy - methods; Female; Humans; Learning; Male; Memory; Middle Aged; Mobility disability; Mobility Limitation; Multiple sclerosis; Multiple Sclerosis - complications; Multiple Sclerosis - psychology; Multiple Sclerosis - rehabilitation; Neuropsychological Tests; Single-Blind Method; Virtual reality; Virtual Reality Exposure Therapy - methods
• ISSN: 1551-7144; 1559-2030; 1559-2030
• DOI: 10.1016/j.cct.2024.107630

This paper describes the protocol for a Phase I/II, parallel-group, single-blind randomized controlled trial (RCT). The RCT investigates the combined effects of 12-weeks of aerobic exercise training (AET) integrated with virtual reality (VR) and cognitive rehabilitation (CR) on new learning and memory in 78 persons with multiple sclerosis (MS) who have mobility disability and objective impairments in learning and memory. Participants will undergo baseline assessments consisting of neuropsychological testing, neuroimaging, self-report questionnaires, and cardiorespiratory fitness. Participants will then be randomized into one of two conditions using concealed allocation: aerobic cycling exercise that incorporates VR combined with CR or stretching and toning (i.e., active control; S/T) combined with CR. Participants will be masked regarding the intent of the conditions. After 7-weeks of exercise alone, the 5-week Kessler Foundation modified Story Memory Technique (KF-mSMT®) will be integrated into the training. After the 12-week training period, participants will complete the same measures as at baseline administered by treatment-blinded assessors. Primary study outcomes include new learning and memory (NLM) measured by a small battery of neuropsychological assessments that assess list learning (California Verbal Learning Test-II), prose memory (Memory Assessment Scale), visuospatial memory (Brief Visuospatial Memory Test-Revised), and everyday memory (Ecological Memory Simulations). Secondary study outcomes include neuroimaging outcomes of hippocampal structure, function, and connectivity. If successful, this trial will provide the first Class I evidence supporting the unique combination of aerobic cycling exercise with VR and CR for treating MS-related learning and memory impairments in persons with mobility disability. •The impact of cognitive impairment in MS increases with greater disease progression (i.e., mobility disability).•Cognitive rehabilitation effectively improves one specific domain of learning and memory (i.e., list-learning).•Combining cognitive rehabilitation and aerobic exercise may lead to bigger and broader cognitive improvements.•Adding virtual reality to exercise may further improve learning and memory by increasing the multisensory demand.•This trial will provide Class I evidence supporting this combinatory treatment for MS-related learning and memory.