Magnetic Resonance Spectroscopy Study of Memantine in Alzheimer's Disease

Summary

We are studying subjects with mild to moderate Alzheimer's disease who have been on a stable dose of any cholinesterase inhibitor \[donepezil (Aricept), rivastigmine (Exelon), or galantamine (Razadyne)\] for at least 3 months, and have not previously taken memantine (Namenda). This is an open-label study, with magnetic resonance spectroscopy (MRS) as the primary outcome measure, along with neuropsychological testing, and optional lumbar puncture, evaluating patients on their stable dose of a cholinesterase inhibitor over 24 weeks, followed by another 24 weeks on memantine in combination with stable dose of cholinesterase inhibitor. The purpose of this study is to characterize the progression of disease using MRS, cerebrospinal fluid (CSF) biomarkers, and cognitive outcome measures, and to determine whether changes in cognitive function on neuropsychological testing are correlated to changes in MR spectroscopic and/or CSF biomarkers.

Timeline

Start

2007-08

Primary completion

2011-12

Completion

2011-12

Publications

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• Background Huang W, Alexander GE, Chang L, Shetty HU, Krasuski JS, Rapoport SI, Schapiro MB. Brain metabolite concentration and dementia severity in Alzheimer's disease: a (1)H MRS study. Neurology. 2001 Aug 28;57(4):626-32. doi: 10.1212/wnl.57.4.626.
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• Background Lin A, Ross BD, Harris K, Wong W. Efficacy of proton magnetic resonance spectroscopy in neurological diagnosis and neurotherapeutic decision making. NeuroRx. 2005 Apr;2(2):197-214. doi: 10.1602/neurorx.2.2.197.
• Background Linker G, Mirza N, Manetti G, Meyer M, Putnam KT, Sunderland T. Fine-needle, negative-pressure lumbar puncture: a safe technique for collecting CSF. Neurology. 2002 Dec 24;59(12):2008-9. doi: 10.1212/01.wnl.0000038360.01635.39. No abstract available.
• Background Miguel-Hidalgo JJ, Alvarez XA, Cacabelos R, Quack G. Neuroprotection by memantine against neurodegeneration induced by beta-amyloid(1-40). Brain Res. 2002 Dec 20;958(1):210-21. doi: 10.1016/s0006-8993(02)03731-9.
• Background Modrego PJ, Fayed N, Pina MA. Conversion from mild cognitive impairment to probable Alzheimer's disease predicted by brain magnetic resonance spectroscopy. Am J Psychiatry. 2005 Apr;162(4):667-75. doi: 10.1176/appi.ajp.162.4.667.
• Background Rose SE, de Zubicaray GI, Wang D, Galloway GJ, Chalk JB, Eagle SC, Semple J, Doddrell DM. A 1H MRS study of probable Alzheimer's disease and normal aging: implications for longitudinal monitoring of dementia progression. Magn Reson Imaging. 1999 Feb;17(2):291-9. doi: 10.1016/s0730-725x(98)00168-4.
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• Background Waldman AD, Rai GS. The relationship between cognitive impairment and in vivo metabolite ratios in patients with clinical Alzheimer's disease and vascular dementia: a proton magnetic resonance spectroscopy study. Neuroradiology. 2003 Aug;45(8):507-12. doi: 10.1007/s00234-003-1040-y. Epub 2003 Jul 22.

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