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

Abstract

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.

Glucocerebrosidase mutations and the pathogenesis of Parkinson disease

“…There were GD individuals with significant motor findings identified using the UPDRS part III, but these did not overlap with existing bone or joint abnormalities. Cognitive dysfunction has been reported in Type I GD, and substrate reduction therapy (SRT) may induce memory problems (Elstein et al, 2005). However, only 2 GD patients were receiving SRT when evaluated at baseline and at follow-up, and neither had cognitive impairment.…”

Oral maintenance clinical trial with miglustat for type I Gaucher disease: switch from or combination with intravenous enzyme replacement

“…The context for this is important, because trials with miglustat had been halted at our center because of concern of cognitive decline in one patient. 26 Because of this concern, during a 3-month period, all trial patients as well as other patients underwent comprehensive neuropsychologic testing; then there was a further 3-month hiatus by the manufacturer before treatment was reinstated. Key disease parameters based on calculation for remaining disease, as described in "Statistical analysis."…”

No justification for very high‐dose enzyme therapy for patients with type III Gaucher disease

“…Should the authors or others continue to follow these type III patients, i.e. as they are reduced from very high doses of ERT and/ or are enrolled into a new trial with this or another SRT or with new pharmacological chaperones, perhaps an attempt should be made to use a simple computer-based tool for cognitive performance (Elstein et al 2005).…”