Treating cognitive deficits in multiple sclerosis

Abstract

[In] most of the patients affected by multi-locular sclerosis, there is marked enfeeblement of the memory. — —Charcot (1877) Neuropsychological studies have consistently demonstrated that 40 to 65% of patients with multiple sclerosis (MS) experience cognitive dysfunction, particularly in recent memory, information processing speed, and sustained attention.1 Cognitive deficits occur in all MS subtypes, are evident at the earliest stages of MS, and tend to worsen over time.1,2⇓ Deficits correlate with lesion burden and brain atrophy. Localized lesions lead to specific deficits (e.g., frontal lesions associated with executive dysfunction).1 Deficits in cognition can have a deleterious effect on activities of daily living that appear to be independent of severity of physical disability.3 Despite its high prevalence and impact on quality of life, there are currently no proven symptomatic pharmacologic treatments for this problem. Disease modifying therapies (DMT) may reduce the development of new lesions and therefore prevent or minimize the progression of cognitive decline (although actual improvements are also possible if inflammatory mediators are causing reversible dysfunction). Cognitive tests have been used to evaluate the effects of DMT in clinical trials with mixed results.4,5⇓ Only a handful of open label or small controlled studies have evaluated symptomatic treatments for cognitive deficits in MS. Initial studies of 4-aminopyridine, amantadine, and pemoline have been largely negative. Even though MS is not known to have primary cholinergic deficits, there are reasons …