The xanthine derivative denbufylline has been evaluated in the treatment of
cognitive dysfunction in 110 patients with vascular or mixed dementia (VD)
and 226 patients with dementia of the Alzheimer type (DAT). After a run-in
period of 4 weeks, during which all patients received placebo, the patient
s were randomly allocated to denbufylline 25, 50 or 100 mg or to placebo gi
ven twice daily for 16 weeks. By the end of the study (completed by 68% of
the patients), but also at enrollment, the scores obtained on the Mini-Ment
al State Examination (MMSE) were higher among those who had received denbuf
ylline than among those who had received placebo, but the differences were
not statistically significant; a dose effect of denbufylline was not observ
ed and there was no significant difference in the mean scores of the digit
substitution subtest (DSST) of the Wechsler memory test. The responses of p
atients with VD were similar to those of patients with DAT. When patients w
ere compared in terms of those who received denbufylline versus those who r
eceived placebo, improvement in the MMSE scares was observed in 46% of the
patients who received placebo and 67% among those who received denbufylline
(p < 0.05). An inverse relationship was found between the improvement that
occurred during the run-in period a nd th at observed by the end of the st
udy, had the patients received denbufylline or placebo. No major adverse ev
ent was ascribed to denbufylline. In conclusion, denbufylline was not deeme
d efficacious in the treatment of DAT or VD, although patients who received
denbufylline tended to improve in terms of cognitive scores, but the effec
ts were not statistically significant. MMSE scores were found to be higher
among patients who received denbufylline when these latter were combined as
a single group, regardless of their diagnosis or dosage regimen. A placebo
effect was observed in about half the patients who completed the study. Co
pyright (C) 1999 S. Karger AG. Basel.