Discussion
The results of this pilot double-blind, randomized, placebo-controlled trial of riluzole 50 mg twice daily in patients with Alzheimer's disease have confirmed our primary hypotheses, showing 6 months of riluzole treatment to be associated with less decline in FDG-PET measures of cerebral glucose metabolism compared to placebo. The effect was most robust in PC, but effects were also observed in precuneus, lateral temporal cortex, right hippocampus and frontal cortex. Glutamate levels measures with 1H MRS, a secondary outcome, showed a significant or trend-level group × visit interaction in PC, whereby the levels of this excitatory amino acid neurotransmitter increased after three months of treatment, suggesting the possibility that riluzole engages the glutamatergic system as its therapeutic target. No changes were found in the 1H MRS levels of NAA, our second primary outcome measure. A significant correlation was observed between cognitive measures and cerebral metabolism in FDG-PET, a key measure of brain function in Alzheimer's disease. PC glutamate levels also correlated with cognitive performance. Our study provides the first in-human data supporting a potential therapeutic benefit of riluzole in patients with Alzheimer's disease.
The beneficial effects of riluzole on neuronal function and cognition observed in this pilot study could be attributable to one or more of the mechanisms that have been established in rodent models.
