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Treatment of Cognitive Impairment in Multiple Sclerosis

Is the Use of Acetylcholinesterase Inhibitors a Viable Option?

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Abstract

Approximately half of all patients with multiple sclerosis (MS) experience cognitive impairment, most commonly with regard to new learning and memory. Cognitive dysfunction is a leading cause of disability in MS and it can have profound social and economic consequences for patients and their families.

Research on treatment for cognitive impairment in MS is still in the early stages, as it is for most neurological conditions. The available disease-modifying therapies in MS may provide some modest benefit to cognition, but patients with MS clearly need better treatment for cognitive dysfunction. A number of studies have assessed symptomatic treatments of cognition in MS, and the results of these small, underpowered studies have been mixed. Regardless, acetylcholinesterase inhibitors (AChEIs) have been the most promising class of medications tested in MS to date. Seven of eight studies on AChEIs have shown positive results, although it is difficult to assess their adequacy. Only three of the AChEI studies have been published in peer reviewed journals, with the rest appearing only as abstracts. The earliest AChEI studies in MS examined physostigmine, but the short half-life and prominent adverse effects of this medication may have limited its use compared with other AChEIs. All of the more recent AChEI studies have used donepezil, which, from the limited data available to date, appears to have been relatively well tolerated among MS patients. The largest randomized controlled trial of donepezil included 69 subjects and found that donepezil improved verbal learning and memory compared with placebo during neuropsychological testing. That study also found that patients receiving donepezil were more likely to report memory improvement than those receiving placebo, and the study clinician also noted a cognitive benefit among those on donepezil as opposed to placebo.

There are still many unanswered questions regarding the use of AChEIs in MS, including the effects of their long-term use in a chronic disease such as MS. On the whole, to date the research on AChEIs in MS must be considered preliminary, and it is premature to recommend the clinical use of this class of medications at the present time.

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Acknowledgements

Supported by the National Institutes of Health (grant no. HD38107-01), the National Institutes for Disability and Rehabilitation Research (grant no. H133G990058), the National Multiple Sclerosis Society (grant no. RG3042-A-2) and the National Center for Research Resources (grant no. M01-RR10710-02). The authors have no conflicts of interest that are directly relevant to the content of this review.

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  1. Department of Neurology, State University of New York at Stony Brook, HSC T12-028, Stony Brook, New York, 11794-8121, USA

    Christopher Christodoulou, Nancy A. McLinskey & Lauren B. Krupp

  2. Department of Neurology, Comprehensive Epilepsy Center, New York University, New York, New York, USA

    William S. MacAllister

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  1. Christopher Christodoulou
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  2. William S. MacAllister
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Correspondence to Christopher Christodoulou.

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Christodoulou, C., MacAllister, W.S., McLinskey, N.A. et al. Treatment of Cognitive Impairment in Multiple Sclerosis. CNS Drugs 22, 87–97 (2008). https://doi.org/10.2165/00023210-200822020-00001

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