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Research paper
Longitudinal multimodal imaging in mild to moderate Alzheimer disease: a pilot study with memantine
  1. R Schmidt1,2,
  2. S Ropele1,
  3. B Pendl1,
  4. P Ofner3,
  5. C Enzinger1,
  6. H Schmidt4,
  7. A Berghold3,
  8. M Windisch5,
  9. H Kolassa6,
  10. F Fazekas1
  1. 1
    Department of Neurology, Medical University of Graz, Austria
  2. 2
    Divisions of Neuroradiology and Nuclear Medicine, Medical University of Graz, Austria
  3. 3
    Department of Radiology, Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Austria
  4. 4
    Institute for Molecular Biology and Biochemistry, Medical University of Graz, Austria
  5. 5
    JSW Research, Forschungslabor GmbH, Graz, Austria
  6. 6
    Merz Pharma Austria GmbH, Vienna, Austria
  1. R Schmidt, Department of Neurology, Medical University of Graz, Auenbruggerplatz 22, A-8036 Graz, Austria; reinhold.schmidt{at}meduni-graz.at

Abstract

Objective: To study the feasibility of multimodal neuroimaging in mild to moderate Alzheimer disease (AD) and to estimate the size of possible treatment effects of memantine on potential functional, structural and metabolic biomarkers of disease progression.

Methods: In this randomised, double-blind, placebo-controlled pilot study, 36 patients with moderate AD received 52 weeks of memantine (20 mg/day) or placebo. Patients were re-evaluated after 26 and 52 weeks to measure the change from baseline in several outcome measures including global and regional glucose metabolism, total brain and hippocampal volumes, as well as chemical shift imaging-derived global and regional N-acetylaspartate and myoinositol concentrations.

Results: In the total population, global glucose metabolism decreased by 2.3% (p<0.01), total brain volume by 2.1% (p<0.001) and hippocampal volume by 2.7% (p<0.01) after 52 weeks. Chemical shift imaging (CSI) spectra were severely affected by patient-induced artefacts and highly variable. Patients receiving memantine showed less decline in glucose metabolism in all brain areas than patients on placebo. Their loss of hippocampal volume was substantially smaller (2.4% vs 4.0%). No between-group differences were seen for changes in total brain volume.

Conclusions: The results support the use of multimodal imaging including MRI and positron emission tomography (PET) to monitor the progression of moderate AD. CSI yielded unreliable longitudinal results. The data suggest that memantine has potentially protective effects in AD and they can be used for planning larger confirmatory studies on the cerebral effects of memantine.

https://doi.org/10.1136/jnnp.2007.141648

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    Footnotes

    • Funding: The study was sponsored by Merz Pharma Austria GmbH.

    • Competing interests: RS has received compensation for lectures, consulting fees and research funding from the sponsor of the reported study. MW has received consulting fees and research funding, and acted on behalf of the sponsor of the reported study. HK was a general manager at Merz Pharma Austria GmbH acting as sponsor of the reported study. FF has received consulting fees, reimbursement and research funding (including funds for a staff member) from the sponsor of the reported study.

    • Ethics approval: None of the patients included in the trial could obtain licensed treatment at study entry or would be withheld such treatment during the study, hence the local ethics committee approved a 1-year placebo-controlled trial. Written informed consent was obtained from the patients and their caregivers.