Computerized cognitive testing in patients with type I Gaucher disease: effects of enzyme replacement and substrate reduction

Genet Med. 2005 Feb;7(2):124-30. doi: 10.1097/


Purpose: Because of concern for drug-induced cognitive dysfunction during clinical trials using substrate reduction therapy (miglustat) in type 1 Gaucher disease and because it has been suggested that some patients with type 1 Gaucher disease may develop neurocognitive impairment as part of the natural history, two different batteries of neuropsychological tests were devised to examine these issues. Using these tests, cognitive function was assessed in patients treated with miglustat, in patients receiving enzyme replacement (standard care for symptomatic patients), and in untreated (milder) patients.

Methods: For this study, 55/60 patients exposed to miglustat in Israel participated in psychologist-administered testing; 36/55 participated in computerized testing. Of these, 31 enzyme-treated patients and 22 untreated patients participated in the psychologist-administered testing, and 15 enzyme-treated patients and 18 untreated patients participated in computerized testing. The psychologist-administered battery consisted of 18 standard neuropsychological subtests specific to executive and visuospatial functioning. The computerized battery (Mindstreams, NeuroTrax Corp., New York, NY) consisted of 10 subtests tapping multiple cognitive domains. Between-group analyses for each modality compared cognitive performance.

Results: In the psychologist-administered testing, patients exposed to miglustat performed significantly less well than the other groups in 5/18 subtests. On the computerized tests, all patients performed comparably to normal controls. Scores in patients exposed to miglustat were higher than in untreated patients, particularly in visuospatial function, whereas enzyme-treated patients performed less well. However, with the exception of visuospatial function, these results were not statistically significant.

Conclusions: It is unclear why different testing methods yielded discordant results. Any dysfunction suggested by the current study is apparently subtle and of doubtful clinical relevance given that cognitive status did not interfere with patients' daily intellectual function. The computerized battery has methodological advantages (e.g., language options, objectivity, brevity, and ease of use) that make it well-suited for longitudinal studies, for long-term surveillance of substrate reduction therapy as well as for comparisons with other lysosomal storage disorders and other chronic diseases. These preliminary findings should allay fears of cognitive dysfunction due to short-term miglustat therapy.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Deoxynojirimycin / adverse effects*
  • 1-Deoxynojirimycin / analogs & derivatives*
  • 1-Deoxynojirimycin / therapeutic use*
  • Adult
  • Aged
  • Cognition Disorders / diagnosis
  • Cognition Disorders / drug therapy*
  • Enzyme Inhibitors / adverse effects*
  • Enzyme Inhibitors / therapeutic use*
  • Female
  • Gaucher Disease / complications
  • Gaucher Disease / drug therapy*
  • Gaucher Disease / psychology*
  • Humans
  • Intelligence Tests
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Observer Variation
  • Psychometrics
  • Reproducibility of Results
  • User-Computer Interface


  • Enzyme Inhibitors
  • 1-Deoxynojirimycin
  • miglustat