Treatment of Memory Impairment in Multiple Sclerosis
There is currently no FDA-approved pharmacological treatment for memory impairment in MS, and the evidence does not support routine use of acetylcholinesterase inhibitors or supplements for this indication. 1, 2
Disease-Modifying Therapies as First-Line Approach
The most important intervention is optimizing disease-modifying therapy (DMT) to prevent further cognitive decline. The nine classes of DMTs approved for relapsing-remitting MS can reduce inflammatory activity that contributes to cognitive dysfunction, though their direct cognitive benefits are modest. 3
- DMTs reduce annual relapse rates by 29-68% compared to placebo, which may indirectly stabilize or possibly improve cognition by controlling disease progression. 3, 4
- Timely and adequate DMT treatment in relapsing-remitting MS may stabilize cognition, as cognitive dysfunction correlates with MRI lesion volumes and brain atrophy that DMTs can reduce. 4
Acetylcholinesterase Inhibitors: Preliminary Evidence Only
Donepezil has shown the most promise in small studies but remains investigational and cannot be recommended for routine clinical use. 1
- Seven of eight studies on acetylcholinesterase inhibitors showed positive results in MS-related cognitive impairment, with donepezil being the most studied agent. 1
- The largest randomized controlled trial (n=69) found donepezil improved verbal learning and memory compared to placebo, with patients more likely to report subjective memory improvement. 1
- Critical limitation: Only three studies have been published in peer-reviewed journals, with the rest appearing only as abstracts, making the evidence base inadequate for clinical recommendations. 1
- Long-term effects in chronic MS remain unknown, and the research must be considered preliminary. 1
Supplements: Not Recommended
Vitamin and supplement interventions lack evidence for cognitive improvement in MS and should not be used for this indication. The dementia literature provides relevant context:
- Omega-3 fatty acids, B vitamins (B1, B6, B12, folic acid), vitamin E, vitamin D, selenium, and copper supplements are not recommended for cognitive impairment prevention or correction. 5
- These recommendations apply unless there is documented deficiency of specific vitamins. 5
Address Comorbidities First
Before attributing memory problems solely to MS, recognize and treat depression and fatigue, which commonly aggravate cognitive symptoms. 2, 4
- Depression, anxiety, and fatigue significantly worsen cognitive symptoms in MS patients. 4
- Treating these comorbidities is the first step in managing cognitive dysfunction. 2
- Antianxiety medications may paradoxically worsen memory dysfunction and should be used cautiously. 6
Non-Pharmacological Interventions
Cognitive rehabilitation, occupational therapy, and leisure activities represent the current mainstay of symptomatic treatment. 2, 4
- Cognitive rehabilitation in MS is still developing but shows promise. 4
- Leisure activities enhance cognitive reserve and may provide protective effects. 4
- Cognitive behavioral therapy, exercise programs, and education interventions improve coping and lessen cognitive symptoms. 4
Clinical Context and Monitoring
Memory impairment affects 40-65% of MS patients, typically involving complex attention, information processing speed, episodic memory, and executive functions. 4 Once cognitive dysfunction develops, it is unlikely to remit without intervention. 2 The Brief Repeatable Neuropsychological Battery and Symbol Digit Modalities Test serve as screening tools, while formal evaluation uses the Minimal Assessment of Cognitive Function in MS. 4