An Open-Label Exploratory Study with Memantine: Correlation between Proton Magnetic Resonance Spectroscopy and Cognition in Patients with Mild to Moderate Alzheimer’s Disease

Abstract

Aim: To characterize progression of Alzheimer’s disease (AD) using proton magnetic resonance spectroscopy (1H MRS). Methods: Eleven subjects with mild to moderate AD underwent neurocognitive testing and single-voxel 1H MRS from the precuneus and posterior cingulate region at baseline, after 24 weeks of monotherapy with a cholinesterase inhibitor, and after another 24 weeks of combination therapy with open-label memantine and a cholinesterase inhibitor. Baseline metabolites [N-acetylaspartate (NAA), myo-inositol (mI), choline (Cho), and creatine (Cr)] and their ratios in AD subjects were compared with those of an age-matched control group of 28 cognitively normal subjects. Results: AD subjects had significantly higher mI/Cr and lower NAA, NAA/Cr, NAA/Cho, and NAA/mI. Baseline Alzheimer’s Disease Cooperative Study Activities of Daily Living (ADCS-ADL) scores significantly correlated with NAA/Cr, mI/Cr, and NAA/mI. There was an increase in mI and a decrease in NAA/mI, but no significant change in other metabolites or ratios, or neurocognitive measures, when memantine was added to a cholinesterase inhibitor. Conclusion: Metabolite ratios significantly differed between AD and control subjects. Baseline metabolite ratios correlated with function (ADCS-ADL). There was an increase in mI and a decrease in NAA/mI, but no changes in other metabolites, ratios, or cognitive measures, when memantine was added to a cholinesterase inhibitor.

Keywords

• Magnetic resonance spectroscopy
• Alzheimer’s disease
• Activities of daily living
• Image biomarker
• Memantine
• Cholinesterase inhibitors