نقش فعالیت ورزشی بر عملکرد عصبی-عضلانی در سالمندان مبتلا به مالتیپل اسکلروزیس: مرور پیشینه و جهت گیری های پژوهشی

Background:
Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system, typically diagnosed between the ages of 20 and 50. However, demographic and clinical trends reveal a rising prevalence of older adults living with MS, with estimates suggesting that approximately 30% of people with MS are now over the age of 60. In this aging population, neuromuscular function is substantially compromised due to a synergistic effect of disease progression, age-related musculoskeletal decline, and reduced physical activity. Consequently, exercise-based interventions have gained attention as non-pharmacological strategies to mitigate these deficits and promote functional independence.

Objective:
This review summarizes the effects and underlying mechanisms of aerobic, resistance, and combined training on neuromuscular function in older adults with MS. It further highlights current gaps in the literature and outlines directions for future research and clinical implementation.

Key Mechanisms and Findings:
Resistance training has emerged as a core modality in neurorehabilitation for aging individuals with MS. Beyond improvements in muscle strength, it enhances neuromuscular coordination, balance, and reduces fatigue. From a neurobiological standpoint, resistance training may stimulate dopaminergic, serotonergic, and noradrenergic systems, thereby contributing to mood regulation and cognitive function. Additionally, it promotes neuroplasticity and neurogenesis in brain areas such as the hippocampus and motor cortex. Myokine release (e.g., IL-6, BDNF, irisin) from skeletal muscle during resistance exercise facilitates muscle-brain crosstalk and may modulate MS-related neuroinflammation. Furthermore, anabolic hormone responses (e.g., testosterone, GH, IGF-1) support muscular and neural tissue repair.

Optimal resistance training for this population includes 2–3 sessions per week on non-consecutive days, starting with low to moderate intensity (40–60% 1RM) and progressing up to 60–80% 1RM, 1–3 sets of 8–12 repetitions per major muscle group.

Aerobic training, meanwhile, offers both peripheral and central benefits. Physiologically, it improves cardiovascular fitness and muscular endurance. Neurologically, aerobic exercise has been shown to elevate levels of neurotransmitters, enhance brain connectivity (particularly interhemispheric and attentional networks), and increase cerebral blood flow. These adaptations are thought to underlie observed improvements in motor function, cognitive performance, and emotional well-being. Functional brain imaging supports these effects, showing increased connectivity in regions related to attention, memory, and motor control after aerobic exercise interventions. Effective aerobic regimens typically involve 20–40 minutes of moderate-intensity activity (40–60% HRR or Borg scale 11–13) such as walking, cycling, or aquatic exercise, performed 2–3 times per week.

Combined training, integrating both aerobic and resistance modalities, is increasingly recognized for its multifaceted impact. This approach targets both central and peripheral limitations caused by MS and aging. Aerobic components facilitate cardiovascular and neuroplastic improvements, while resistance components strengthen muscular function and postural control. When prescribed correctly, combined training is feasible and safe in older adults with MS. Recommended protocols include 15–30 minutes of moderate aerobic activity alongside 1–3 sets of resistance exercises targeting major muscle groups, 2–3 times per week. Program individualization, professional supervision, and gradual progression are critical for accommodating disease heterogeneity, fatigue levels, and physical limitations.

Gaps and Research Directions:
Despite promising evidence, several critical gaps remain. Firstly, most exercise studies in MS have focused on younger adults, with limited data available specifically for older populations. Secondly, optimal exercise dosage (frequency, intensity, duration) and long-term effects, particularly of combined training protocols, remain unclear. Third, neurobiological mechanisms—especially those related to systemic inflammation, myokine signaling, and neuroplasticity—are underexplored in this subgroup. Moreover, adherence and sustainability of exercise interventions in older adults with MS are poorly studied, despite being key to long-term functional outcomes.

Future research should prioritize randomized controlled trials in aging MS populations, investigate individualized and home-based exercise protocols, and include biomarkers to elucidate underlying mechanisms. Longitudinal studies examining functional independence, fall risk reduction, and quality of life are also warranted.

Conclusion:
Aerobic, resistance, and combined exercise interventions offer substantial benefits for neuromuscular function in older adults with MS through a range of physiological and neurobiological mechanisms. While current evidence supports their implementation as part of comprehensive rehabilitation strategies, more targeted research is required to refine prescriptions and enhance clinical translation. Developing safe, scalable, and tailored exercise programs could play a pivotal role in preserving autonomy and quality of life in this growing clinical population)

Footnotes

Funding: This study received no funding from public, commercial, or non-profit Organizations.

Authors’ contribution: All authors contributed to the design, implementation, and writing of all parts of the present study.

Conflict of interest: The authors declare that there is no conflict.

Acknowledgments: We thank all the researchers who contributed to the writing of this article.