Reducing hippocampal hyperactivity significantly improves cognition in amnestic mild cognitive impairment (aMCI), report US researchers who say that targeting excess hippocampal activity may therefore have therapeutic potential.
Elevated hippocampal activation is observed in conditions that confer risk for Alzheimer’s disease, including aMCI, explain Michela Gallagher from John Hopkins University in Baltimore, Maryland and co-investigators in the journal Neuron.
“In the case of aMCI, it has been suggested that the increased hippocampal activation may serve a beneficial function by recruiting additional neural ‘resources’ to compensate for those that are lost,” Gallagher explained. “However, animal studies have raised the alternative view that this excess activation may be contributing to memory impairment.”
To investigate further, the team tested the effect of reducing hippocampal activation in patients with aMCI by administering a low-dose of levetiracetam, a drug used to treat epilepsy.
The goal was to reduce the hippocampal activity of the participants to levels that were similar to those of healthy, age-matched controls. Functional magnetic resonance imaging was then used to determine the levels of excess activity, and any drug-related reductions.
Gallagher et al found that low-dose levetiracetam reduced hippocampal activation to a level that did not differ significantly from the control group.
In addition, compared with aMCI memory performance at baseline, task-related memory performance was significantly improved under drug treatment.
“Contrary to the view that greater hippocampal activation might serve a beneficial function, these results support the view that increased hippocampal activation in aMCI is a dysfunctional condition and that targeting excess hippocampal activity has therapeutic potential,” concludes the team.
The findings may have broad clinical implications because increased hippocampal activation occurs not only in patients with aMCI, but also in other neurodegenerative diseases, such as familial Alzheimer’s disease.
By Nikki Withers