Cholinesterase inhibitor plus memantine yields neurological benefits for patients with Alzheimer’s

PHILADELPHIA — For patients with Alzheimer’s disease, adding memantine to cholinesterase inhibitor therapy reduced neuropsychiatric symptoms and improved cognition, according to abstracts presented at the American Academy of Neurology Annual Meeting.

Lessens neuropsychiatric symptoms

Using three phase 3, randomized, double-blind, placebo-controlled trials, researchers pooled data from participants with moderate to severe Alzheimer’s disease (n = 1,262; mean age, 75.7 years) to examine the effect of memantine with cholinesterase vs. cholinesterase inhibitor therapy alone on four behavioral syndrome domain scores of the Neuropsychiatric Inventory (psychosis, neurovegetative, frontal and mood).

They found that the combination of memantine and cholinesterase inhibitors both reduced psychosis (agitation/aggression, hallucinations, delusions, irritability) and improved neurovegetative scores (aberrant motor behavior, nighttime behavior, appetite/eating change) at 12 and 24 weeks compared with cholinesterase and placebo.

“There is a lot of developmental work in terms of psychosis — agitation, sleep disorders, apathy — and a lot of attention paid to behavioral disturbances in Alzheimer’s disease,” Jeffrey L. Cummings, MD, director of the Cleveland Clinic Lou Ruvo Center for Brain Health, told Healio Primary Care. “That’s a rich pipeline, and we will have new treatments. These kind of analyses of existing treatments inform us of how best to analyze the data that are coming from the new trials.”

‘Persistent’ benefits to cognition

Again pooling data from three previous trials, researchers evaluated the effect of memantine with cholinesterase inhibitors on total Severe Impairment Battery and the higher-order cognitive domains of memory, language and praxis.

“Memantine is approved for moderate to severe Alzheimer’s disease, which is why the Severe Impairment Battery was used in these studies,” Cummings said. “These patients are struggling with cognition, so you need a tool that they can respond to in order to have a measurable result.”

Researchers found that, compared with cholinesterase alone, participants who were also prescribed memantine had improved Severe Impairment Battery scores and also saw improvements for memory, language and praxis.

The differences between combination therapy and cholinesterase inhibitor only were “persistent” for the entire 24 weeks of the study, Cummings added.

“It wasn’t something that was coming and going. Rather, for patients who had benefit, that benefit was consistent over the course of the trial,” he said.

“If physicians and clinicians have their patients on both therapies, they’re more likely to see benefit than if a patient is on only a cholinesterase inhibitor,” Cummings added. – by Melissa J. Webb

References:

Cummings JL, et al. The effects of memantine added to cholinesterase inhibitors on NPI behavioral domains: Pooled post hoc analysis of 3 randomized controlled trials in patients with moderate to severe AD.

Schmitt FA, et al. Efficacy of memantine added to cholinesterase inhibitors on SIB higher-order cognitive domains: Pooled post hoc analysis of 2 randomized controlled trials in patients with moderate to severe AD.

Schmitt FA, et al. SIB maintenance of response with memantine added to cholinesterase inhibitors: Pooled post hoc analysis of 2 randomized controlled trials in patients with moderate to severe AD.

All presented at: American Academy of Neurology Annual Meeting; May 4-10, 2019; Philadelphia.

Disclosure: Healio Primary Care could not confirm relevant financial disclosures at the time of publication.