Cognitive dysfunction in multiple sclerosis: natural history, pathophysiology and management

Cognitive dysfunction is a major cause of disability in patients with multiple sclerosis (MS). The prevalence of cognitive dysfunction is estimated at 45 to 65%. Natural history studies suggest that once cognitive dysfunction develops in a patient with MS, it is not likely to remit. Unlike physical disability in MS, cognitive disability correlates weakly with T2 lesion burden on brain magnetic resonance imaging (MRI). More robust correlations exist with magnetisation transfer imaging and MRI measures of brain atrophy. Patients with MS who have cognitive impairment most commonly display deficits in the cognitive domains of memory, learning, attention and information processing. In diagnosing cognitive dysfunction in a patient with MS, it is important first to recognise and treat the common comorbidities of fatigue and depression. The first step in the treatment of cognitive dysfunction is to delay disease progression, and there are currently five such disease-modifying agents approved for the treatment of MS (two preparations of interferon-beta-1a, interferon-beta-1b, glatiramer acetate and mitoxantrone). Nonpharmacological measures, such as cognitive rehabilitation, occupational therapy and psychotherapy, are the mainstays of symptomatic treatment. Pharmacological symptomatic therapy centres on the treatment of comorbid fatigue and depression. There are currently no effective pharmacological agents approved as symptomatic therapy of cognitive dysfunction in MS.