scores. Few studies have used MRS in mild cognitive deficit. Ml/Cr was found to be higher in MCI subjects113, 114 and NAA lower in A AMI subjects115 and AD patients than in controls, whereas MI values were intermediate between AD patients and controls.115 Follow-up studies are necessary to confirm the predictive value of such findings. The magnetization transfer imaging (MTI)116 signal arises from the magnetization exchange between waterand macromolecule -bound protons; this technique is useful in the study of membranes and membrane-linked diseases such as

multiple sclerosis, in which decreased magnetic transfer ratio (MTR) is a marker of demyelination117 Inhibitors,research,lifescience,medical and axonal medical density loss.118 MTI studies involving AD patients119-125 agree on decreased Inhibitors,research,lifescience,medical values compared with NCs, expressing structural changes in the temporal lobe, and also the frontal lobe and the whole brain.119-120 Hippocampal MTR had a discrimination rate relative to controls of 85% in mild AD (CDR=0.5), 89% in mild AD (CDR=1), and 100% in moderate AD (CDR=2); the values for visually rated atrophy were of 73%, 80%, and 91% respectively.124 MTR was also able to differentiate Inhibitors,research,lifescience,medical AD from non-AD dementia with a success rate of 77%.123 Studies comparing MCI subjects with AD patients and healthy controls119-122

identified structural changes in MCI in the absence of significant, atrophy; they were Inhibitors,research,lifescience,medical located in gray matter, whereas those found in AD patients involved white and gray matters.122 These changes were found to be correlated with cognitive impairment.119-120 MTI thus seems able to identify structural changes before atrophy is manifest. Follow-up studies should confirm

its Inhibitors,research,lifescience,medical predictive value and comparison with functional imaging should assess which technique detects the earlier changes. The ApoE ε4 allele is acknowledged to be a risk factor for AD.126, 127 Few studies have specifically addressed its influence on the evolution of MCI subjects. The ApoE ε4 carrier status was found the best predictor of conversion to AD (risk ratio=4.36),21 a nonsignificant predictor (relative risk of 1 .49)79 or to have no predictive value.54, 128 In subjects with memory impairment and Global Deterioration next Scale (GDS) score of 2 to 3,129 ApoE ε4 alone predicted progression to dementia with a 73.8% accuracy; combining genotype and memory scores increased the accuracy to 92.5%. In subjects with MMSE, scores of 21 to 26, the ApoE, genotype was found to be associated with an odds ratio for progression to dementia of 3.31130 and with memory decline.131 Among the various substances that have been assayed in blood and CSF,132 increased CSF-tau and decreased βA1-42 proteins are the best markers for AD to date.