MR spectroscopy for assessment of memantine treatment in mild to moderate Alzheimer dementia

Abstract

Objectives: Magnetic Resonance Spectroscopy (MRS) may provide a precise and reliable assessment of the extent and severity of neural tissue loss caused by various diseases. In particular, the N-Acetyl Aspartate (NAA) and Creatine (Cr) ratio has been found to be an indicator of the degree of neuronal loss in Alzheimer's disease (AD). Memantine is thought to benefit the AD brain by stabilizing the NMDA receptors on neurons in turn reducing excitotoxicity. Despite its effectiveness in treating moderate to severe AD, memantine has not had similar success in the treatment of mildly demented AD patients. The objective of this study was to test whether memantine would slow or prevent the loss of neurons in mild to moderate AD patients.

Methods: A double-blind placebo-controlled study was designed to measure the effect of a year-long course of memantine in patients with a probable AD diagnosis with mild to moderate dementia. The primary outcome measure was stipulated to be change in MRS NAA/Cr ratio in inferior parietal cortex in memantine relative to the placebo treatment condition. The secondary outcome measures were changes in cognitive and function scale scores.

Results: This pilot study failed to demonstrate a benefit of memantine on the primary outcome measure, the inferior parietal NAA/Cr ratio, or the secondary outcome measures.

Conclusions: More studies are needed to determine the effect of memantine on regions of the brain significantly affected by AD pathology.

Fig. 1

MRS scans were performed on a 3 Tesla GE Signa Excite magnet. Voxels were 2×2×2 cm, with centers chosen on a plane 1 cm superior to the plane through the anterior-posterior commissure line, and to include as much gray matter as possible and as little CSF as possible. Three voxels were selected in the Left hemisphere, an inferior parietal voxel, placed as far laterally as possible, behind the sylvian sulcus (shown), an occipital voxel, as posterior as possible, just lateral to the inter-hemispheric sulcus, and a posterior-cingulate voxel, anterior to the occipital cortex and behind the corpus callosum, just lateral to the inter-hemispheric sulcus.