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 study will test the efficacy the B vitamin, nicotinamide (NA, also known as niacinamide), in patients with mild to moderate Alzheimers disease (AD). NA is a member of a class of drugs known as histone deacetylase (HDAC) inhibitors. HDAC inhibitors have recently been shown to be effective in animal models of Parkinsons and Huntingtons disease. We recently found that NA significantly reduced abnormal protein accumulation in the brain of AD transgenic mice while also improving behavioral abnormalities. In this study patients with probable mild to moderate AD will be randomized to receive either NA (1500 mg twice daily by mouth) or placebo for 24 weeks (N = 25 per group). Neurological and physical examinations will be performed at baseline and at the end of the study. Outcome measures will be obtained at baseline and at 6 week intervals up to 24 weeks. The behavioral measures will include the Alzheimers Disease Assessment Scale-Cognitive Subscale (ADAS-cog), Clinicians Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus), Alzheimers Disease Cooperative Study-Activities of Daily Living Scale (ADCSADL), and Clinical Dementia Rating Scale (CDR), some of which are informant-based measures. To assess protein accumulation, lumbar punctures will be performed to collect cerebrospinal fluid (CSF) at baseline and during the final study visit in a subset of 8 subjects from each group. The results from each group will be compared by Student t-test.