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Memantine's Benefits May Extend to Earlier Stages of Alzheimer's Disease: Presented at ANA

By Paula Moyer

TORONTO, ON -- October 8, 2004 -- The Alzheimer's drug memantine (Namenda) may have as much benefit for patients with mild to moderate Alzheimer's disease as it does for patients with more advanced disease, according to findings presented here October 5^th at the American Neurological Association 129^th Annual Meeting.

"In patients with mild to moderate [disease] residing in the community, memantine is superior to placebo in measures of cognition, global status, and behavior," said the study's principal investigator, Steven G. Potkin, MD, Professor of Psychiatry and Human Behaviour, University of California-Irvine.

Positron emission tomography (PET) imaging showed that the study patients had decreased brain metabolism at baseline, he added, but those treated with memantine had statistically significant metabolic increases in areas of the brain where placebo treatment was linked to post-baseline decreases.

"These findings show that memantine monotherapy may stabilise or improve cognitive function in patients at early stages of Alzheimer's," said Dr. Potkin. Such benefits could expand the indications for memantine, which has been approved for moderate to severe disease.

Memantine is a low-moderate affinity uncompetitive n-methyl-d-aspartate (NMDA) receptor antagonist.

Dr. Potkin and co-investigators designed their pilot PET study to see if memantine had effects on regional cerebral metabolism in mild to moderate Alzheimer's disease. Patients had been randomised to 10 mg of memantine twice daily or placebo. They conducted their study at a single site on a subgroup of 10 patients who had taken part in a 24-week, double blind, placebo-controlled multi-site, phase 3 trial involving 403 patients who were at least 50 years old. Mild to moderate Alzheimer's disease was defined by a Mini-Mental State Examination (MMSE) score of 10 to 22.

In the original study, the investigators subsequently assessed all of the patients who had been in the Phase III trial. Their baseline magnetic resonance imaging or computed tomography scans were consistent with probable Alzheimer's disease. They evaluated response to treatment using a Last Observation Carried Forward analysis, which included the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog; P = .003) and the Clinicians' Interview-Based Impression of Change-Plus Caregiver Input (CIBIC-Plus; P = .004)

They found that memantine-treated patients performed significantly better than placebo-treated patients on both primary outcome measures.

For the subgroup analysis, the investigators conducted PET imaging at baseline and at week 24 on 5 memantine-treated patients and 5 placebo-treated patients. The scans of the placebo-treated patients showed declines in glucose metabolism that are typical of Alzheimer's disease in several brain regions. These included the orbital, cingulated, retrosplenial, dorsal lateral prefrontal and inferior and superior parietal cortices, as well as the thalamic, basal ganglia and cerebellar cortical sites.

In these same areas the scans of memantine-treated subjects showed statistically significant metabolic increases, which were documented in particular in the attentional systems, the inferior parietal cortex (which is language-related), and the orbital cortex. Other affected areas included the cingulate, retrosplenial, parahippocampal and cerebellar cortices. Isolated subcortical sites in the thalamus, striatum, and brainstem also showed metabolic increases, Dr. Potkin said.

The findings suggest, "Memantine can reverse regionally-specific metabolic decreases associated with untreated mild to moderate Alzheimer's disease, he said.

He noted that the results support the study's efficacy results, which had shown benefits to treating patients with mild to moderate disease with memantine.

The study was sponsored by Forest Research Institute of Jersey City, New Jersey. Forest Labs markets Namenda in the United States.


[Presentation title: "Memantine monotherapy increases brain metabolism (PET) and effectively treats mild to moderate Alzheimer's disease." Abstract 226]

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