The Effect of Drugs for Alzheimer Disease Assessed by Means of Neuroradiological Techniques

Pedro   J.   Modrego

doi:10.2174/092986706779010289

Abstract

Cholinesterase inhibitors constitute the standard of care for Alzheimers disease in westerncountries. Donepezil, rivastigmine and galantamine had showed similar efficacy according to meta-analysisfrom randomised clinical trials. A mean modest 2 point-improvement has been observed in the Alzheimersdisease Assessment Scale (ADAS). Memantine has emerged as an alternative for advanced stages of the disease.Apart from clinical scales, neuroradiologic techniques have proven useful to assess the effect of these drugs onthe brain of AD patients. Methods. An extensive search for papers dealing with neuroradiological techniques in the assessment of AD drugs has been conducted, especially based on MEDLINE and EMBASE systems. Results. Several techniques have demonstrated to be useful to assess the effects of drugs and diseaseprogression. Magnetic Resonance Imaging (MRI)-based volumetry of the hippocampus showed moreconsistency to monitor progression than clinical variables, and thus, the sample size for clinical trials may bereduced. Donepezil is able to slow progression of atrophy in two controlled studies suggesting aneuroprotective effect Proton Magnetic Resonance Spectroscopy (MRS) measures metabolite concentration of living tissues. In AD the most characteristic findings are decreased N-acetyl aspartate (neuronal marker) and choline-compoundselevation (marker of cell membrane turnover and degradation). A placebo controlled trial showed thattreatment with donepezil increased transiently the NAA/Cr ratio in both hippocampi in AD. Changes inaspartate levels correlated to clinical response to rivastigmine in a non-randomised trial. Some studies evaluated cholinesterase inhibition in vivo with PET (Positron Emission Tomography) withhigher reductions for rivastigmine than for donepezil in several cortical areas. Metabolism of glucose was alsostudied in patients taking galantamine or rivastigmine. Rivastigmine may stabilise glucose metabolism in asmall series of AD patients. Correlation between glucose metabolism and changes in clinical scales has beenobserved in patients treated with galantamine. Most studies point to the frontal cortex as the best area to detectchanges after treatment with cholinesterase inhibitors. Conclusions. Neuroradiologic techniques are of help to evaluate the effect of drugs in AD, and to monitordisease progression.

Keywords: Alzheimer's disease, Effect of drugs, Neuroradiologic techniques

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