Cognitive impairment in multiple sclerosis: An 18 year follow-up study


      • The present study is one of the longest longitudinal studies of cognition in multiple sclerosis (MS).
      • This is a unique sample consisting of individuals from the original Avonex study conducted in the early 1990s.
      • Findings demonstrate the natural evolution of cognitive changes over time in MS.



      Cognitive impairment occurs in 40–65% of patients with multiple sclerosis (MS). Less is known about the rate and pattern of cognitive decline over the course of the illness.


      To examine long-term changes in cognition among patients enrolled in the phase III clinical trial of intramuscular interferon beta-1a (IM IFNβ-1a).


      Twenty-two patients underwent a longitudinal investigation comparing neuropsychological test performance at study entry and 18-year follow-up.


      Over the 18 year interval, significant declines were observed on measures of information processing speed, simple and complex auditory attention, episodic learning and memory, and visual construction. Nine patients (41%) were found to be cognitively impaired at study entry. At follow-up 13 patients (59%) were cognitively impaired. While both the impaired and unimpaired patients at baseline experienced declines on these measures, only one measure, the Symbol Digit Modalities Test (SDMT), demonstrated a group (cognitively impaired versus intact at baseline)×time interaction. This interaction was characterized by a steeper decline in the unimpaired than the impaired group at baseline.


      Over an 18 year period, our results suggest that cognitive impairment in MS progresses, with declines being most evident on measures known to be most sensitive to MS-related cognitive difficulties both cross-sectionally and longitudinally.


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