Modrego_2006_Curr.Med.Chem_13_3417

UNLABELLED: Cholinesterase inhibitors constitute the standard of care for Alzheimer's disease in western countries. Donepezil, rivastigmine and galantamine had showed similar efficacy according to meta-analysis from randomised clinical trials. A mean modest 2 point-improvement has been observed in the Alzheimer's disease 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 on the 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 disease progression. Magnetic Resonance Imaging (MRI)-based volumetry of the hippocampus showed more consistency to monitor progression than clinical variables, and thus, the sample size for clinical trials may be reduced. Donepezil is able to slow progression of atrophy in two controlled studies suggesting a neuroprotective 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-compounds elevation (marker of cell membrane turnover and degradation). A placebo controlled trial showed that treatment with donepezil increased transiently the NAA/Cr ratio in both hippocampi in AD. Changes in aspartate levels correlated to clinical response to rivastigmine in a non-randomised trial. Some studies evaluated cholinesterase inhibition in vivo with PET (Positron Emission Tomography) with higher reductions for rivastigmine than for donepezil in several cortical areas. Metabolism of glucose was also studied in patients taking galantamine or rivastigmine. Rivastigmine may stabilise glucose metabolism in a small series of AD patients. Correlation between glucose metabolism and changes in clinical scales has been observed in patients treated with galantamine. Most studies point to the frontal cortex as the best area to detect changes after treatment with cholinesterase inhibitors.
CONCLUSIONS: Neuroradiologic techniques are of help to evaluate the effect of drugs in AD, and to monitor disease progression.