Cognitive function in relapsing multiple sclerosis: minimal changes in a 10-year clinical trial.
BACKGROUND
Although cognitive impairment is common in patients with multiple sclerosis (MS), its value as a clinical trial endpoint remains uncertain. For example, in the randomized, blinded, pivotal trial of glatiramer acetate (GA) in patients with relapsing MS, improvements occurred in neuropsychological test scores during 2 years of treatment regardless of whether patients received GA or placebo, likely due to practice effects.


OBJECTIVE
To assess long-term changes in neuropsychological status following 10 years of prospective evaluation in a typical immunotherapy trial cohort.


METHODS
Participants in the ongoing open-label GA extension study repeated the Brief Repeatable Battery of Neuropsychological Tests an average of 10.6+/-0.4 years after their initial baseline evaluation.


RESULTS
Mean scores on tests of memory and semantic retrieval were not significantly changed over 10 years of follow-up, but tests of attention showed declines for the group as a whole. Using a threshold of a 0.5 SD decline to define significant worsening, individual tests showed declines in 27-49% of participants and a composite score showed worsening in 19%. Controlling for age, gender, and education level, cognitive tests tended to worsen more in participants with better baseline cognitive test scores and higher EDSS scores. Changes in cognitive test scores during the first 2 years of observation were predictive of 10-year changes.


CONCLUSIONS
Most patients with relapsing MS had stable cognitive performance during 10 years of prospective evaluation, some of which may be related to a therapeutic effect of GA. Because cognitive changes occur slowly on average, they may not be responsive enough to serve as useful endpoints in studies of course-modifying therapies in relapsing MS.
Schwid
Steven R
SR
University of Rochester, Department of Neurology, Rochester, NY 14642, USA. steven_schwid@urmc.rochester.edu
Goodman
Andrew D
AD
Weinstein
Amy
A
McDermott
Michael P
MP
Johnson
Kenneth P
KP
D000328:Adult; D001288:Attention / Q000187:drug effects / Q000502:physiology; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology* / Q000523:psychology; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007806:Language Disorders / Q000188:drug therapy / Q000209:etiology / Q000523:psychology; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy / Q000209:etiology / Q000523:psychology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications* / Q000188:drug therapy* / Q000523:psychology; D009483:Neuropsychological Tests; D010455:Peptides / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D010455:Peptides; D000068717:Glatiramer Acetate