135 CSF-tau levels were found to be higher in MCI than in healthy controls,136-140 lower than141 or similar to139, 140 those found in AD patients. In

follow-up studies, it identified MCI subjects who evolved to AD with a sensitivity of 65% to 68% and a specificity of 100% versus patients with memory complaints142 and 93% versus healthy controls139; baseline values in converters were higher than in nonconvcrtcrs.137 Inhibitors,research,lifescience,medical In one study,139 combining CSF-tau and βA, values did not. improve the predictability obtained with CSF-tau alone. In others, combined CSF-tau/βA1-42 values differentiated converters from healthy controls with 88% sensitivity and 80% specificity138 and from nonconverters with a 90% sensitivity and specificity.140 Medical diagnoses are Pifithrin�� rarely reached using a single marker; most often it results from the combination of different approaches, including thorough clinical evaluation. Once Inhibitors,research,lifescience,medical a consensus is obtained on cutoff values for the different techniques mentioned, it is likely that a combination of different markers for AD will allow early diagnosis with high sensitivity and specificity in individual cases. Therapeutic aspects The final goal of constructing criteria for age-associated mild cognitive deficit,

is to treat, it, and many therapeutic approaches Inhibitors,research,lifescience,medical are available.143-144 Some benefits have been reported, in terms of global stability and improved memory with

the acetylcholinesterase inhibitors (AChEI) donepezil145 and rivastigmine146 and the dopamine receptor agonist/α2 antagonist, piribedil147; trials are underway using Inhibitors,research,lifescience,medical donepezil and vitamin E, rivastigmine, the cyclooxygenase-2 (COX-2) inhibitors celccoxib and rofecoxib with the goal of delaying patients’ progression to dementia144 and the Inhibitors,research,lifescience,medical Ampakine® CX516 with the aim of short-term symptomatic improvement.148 Treating MCI using approaches initially intended for AD premises either that MCI equates to early AD in all cases, which is unlikely, or that the underlying mechanism is the same in both cases, the difference being merely a matter of intensity, which is not. confirmed by neuropathological data. Even if improved criteria others or techniques were able to predict, the progression to AD in a given patient, this strategy deserves discussion. As regards the cholinergic and glutamatergic systems in AD, it has been proposed that, the final deficiency state is preceded, in the early stages, by a hyperactive state149, 150 originating in βA-induced N-methyl-D-aspartate (NMDA) receptor hypersensitivity. It was recently found that the number of choline acetyltransferase (ChAT)-positive neurons in the nucleus basalis of Meynert was no lower in MCI than in NCs.