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  • Journal of the International Neuropsychological Society, Volume 15, Issue 4
  • July 2009, pp. 606-612

Cognitive reserve moderates the negative effect of brain atrophy on cognitive efficiency in multiple sclerosis

  • JAMES F. SUMOWSKI (a1) (a2), NANCY CHIARAVALLOTI (a1) (a2), GLENN WYLIE (a1) (a2) and JOHN DELUCA (a1) (a2) (a3)
  • DOI:
  • Published online: 01 July 2009

According to the cognitive reserve hypothesis, neuropsychological expression of brain disease is attenuated among persons with higher education or premorbid intelligence. The current research examined cognitive reserve in multiple sclerosis (MS) by investigating whether the negative effect of brain atrophy on information processing (IP) efficiency is moderated by premorbid intelligence. Thirty-eight persons with clinically definite MS completed a vocabulary-based estimate of premorbid intelligence (Wechsler Vocabulary) and a composite measure of IP efficiency (Symbol Digit Modalities Test and Paced Auditory Serial Addition Task). Brain atrophy was estimated from measurements of third ventricle width using high-resolution anatomical brain magnetic resonance imaging (magnetization-prepared rapid gradient echo). In a hierarchical regression analysis controlling for age and depressive symptomatology, brain atrophy predicted worse IP efficiency (R2 = .23, p = .003) and cognitive reserve predicted better IP efficiency (R2 = .13, p = .013), but these effects were moderated by an Atrophy × Cognitive Reserve interaction (R2 = .15, p = .004). The negative effect of brain atrophy on IP efficiency was attenuated at higher levels of reserve, such that MS subjects with higher reserve were better able to withstand MS neuropathology without suffering cognitive impairment. Results help explain the incomplete and inconsistent relationship between brain atrophy and IP efficiency in previous research. (JINS, 2009, 15, 606–612.)

Corresponding author
*Correspondence and reprint requests to: James F. Sumowski, Neuropsychology & Neuroscience Laboratory, Kessler Foundation Research Center, 300 Executive Drive, Suite 10, West Orange, New Jersey 07052. E-mail:
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