This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a randomized, placebo-controlled, double blind, multicenter, two-year trial of valproate therapy at a target dose of 10-12 mg/kg/d in 300 outpatients with mild to moderate AD who lack agitation and psychosis at baseline and since onset of illness. Participants will have regular clinic visits as well as telephone contacts for assessment of behavior, cognition, function, safety and tolerability. Valproate was selected because of its possible symptomatic efficacy for agitation in AD, known safety profile in numerous clinical populations, and in view of recent data supporting its neuroprotective potential in AD. The primary hypothesis is that chronic valproate administration to participants with AD who lack agitation and psychosis at baseline will delay the emergence of agitation and/or psychosis. Secondary hypotheses will be addressed as well. The first of these is that chronic valproate administration to participants with AD will attenuate clinical progression of illness measured by reduced rate of cognitive or functional decline. Participants will remain in the study and be followed per protocol for two years even if they discontinue experimental treatment prematurely, in order to examine possible effects on progression of cognitive or functional decline. In addition, the safety and tolerability of chronic low dose therapy will be addressed. Biological specimens will be obtained to study markers selected for their relevance to the disease as well as the postulated mechanism of action of the therapy. MRI scans will be performed prior to experimental treatment and after one year in a subset of participants in order to address possible drug-placebo differences in brain volume measures. After the double-blind phase, there will be a 2-month single-blind placebo-controlled washout phase to address whether withdrawal will result in differential effects on behavior, cognition, function, or global measures of disease severity from month 24 to 26.