Better memory
In the pre-scan assessment, results showed no significant differences in the ability of members of the prucalopride and placebo groups to identify images as being familiar or different.
However, taking prucalopride was associated with significantly improved memory performance in the post-scan recall task.
Compared to the placebo group, participants in the prucalopride group were more accurate in selecting images as familiar vs distractors (P = .029) and in distinguishing images as familiar, novel, or distractors (P = .035).
Functional MRI revealed increased activity in the left and right hippocampus in response to both novel and familiar images among the participants in the prucalopride group in comparison with those in the placebo group.
There was also increased activity in the right angular gyrus in the prucalopride group in comparison with the placebo group in response to familiar images (P < .005).
“Clinically, angular gyri lesions cause language dysfunction, low mood, and poor memory and can mimic dementia or pseudodementia,” the investigators write. They note that the right angular gyrus “shows significantly decreased activity” in mild cognitive impairment.
“Therefore, the increased activity seen in the right angular gyrus following prucalopride administration in our study is consistent with the pro-cognitive behavioural effects we observed,” they add.
Ms. De Cates noted that the dose used in their study was lower than the 2 mg given for constipation.
“At the low dose, there were no differences in side effects between groups and no withdrawals from the prucalopride group for side effects. We are going to try increasing the dose in our next study actually, as we don’t have PET data to tell us what the optimal dose for binding at the receptor should be,” said Ms. de Cates.
“In safety studies, the dose was trialled in healthy volunteers at 4 mg, which was found to be safe, although perhaps less well tolerated than 2 mg,” she said.
Generalizable findings?
Commenting on the research, Vibe G. Frøkjær, MD, adjunct professor, department of psychology, Copenhagen University, Denmark, said the study “highlights a very interesting and much needed potential for repurposing drugs to help cognitive dysfunction.”
He noted that cognitive dysfunction is often associated with psychiatric disorders -- even in states of remission.
“Importantly, as the authors also state, it will be vital to translate these findings from healthy populations into clinical populations,” said Dr. Frøkjær, who was not involved in the research.
“It will also be important to understand if prucalopride adds to the effects of existing antidepressant treatments or can be used as a stand-alone therapy,” he added.
The study was funded by the NIHR Oxford Health Biomedical Research Center and by the Wellcome Center for Integrative Neuroscience. Ms. De Cates has received a travel grant from the Royal College of Psychiatrists/Gatsby Foundation and support from Wellcome. The other authors have relationships with P1vital Ltd, Janssen Pharmaceuticals, Sage Therapeutics, Pfizer, Zogenix, Compass Pathways, and Lundbeck.
A version of this article first appeared on Medscape.com.