TTiis chronic excitotoxicity results in a cognitive deficit due to decrease in signal-to-noise ratio and neuronal death due to chronic insult.19, 20 NMDA receptor antagonists block the influx of calcium resulting in a reduction in intracellular calcium. Consequently, the noise is reduced and the signal is processed. Memantine, an NMDA receptor antagonist, is

currently Inhibitors,research,lifescience,medical being investigated in the treatment of AD. Memantine In a 28-week, double-blind treatment trial comparing 20 mg/day memantine with placebo, 252 participants were randomized and 181 completed the study. Participants had MM’SE scores between 3 and 14, GDS scores of 5 or 6, and Functional Assessment Staging (FAST) greater than 6a. TTttcre was also a 24-wcek open-label extension for 175 participants who completed Inhibitors,research,lifescience,medical the 28-week study. The CIBTC-plus (Clinicians’ Interview-based Impression of Change-plus), ADAS-Activities of Daily Living, Severe Impairment Battery (SIB), and FAST were used to measure outcome.21 Participants on memantine had a slower rate of decline than those find more receiving placebo. During the open-label extension, participants switched to memantine showed a more gradual decline compared with the first 28 weeks Inhibitors,research,lifescience,medical of placebo treatment.22 Serotonergic and dopaminergic pathway: implications for treatment behavioral disturbances Newer

antipsychotics, such as risperidone, are combined serotonin and dopamine antagonists. Most of the newer antipsychotics exhibit strong antagonistic affinity Inhibitors,research,lifescience,medical for the serotonin (5-hydroxytryptamine) receptor 5-HT2.22 Risperidone has been shown to be efficacious in the treatment of psychosis and behavioral disturbances associated with dementia. Katz et al23 evaluated 625 participants in a 12-week, double-blind Inhibitors,research,lifescience,medical treatment study comparing 0.5 to 2 mg/day of risperidone to placebo. Participants had a diagnosis of AD and/or vascular

dementia (73% had AD), FAST scale score of >4, MMSE of <23, Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD) rating of >8 and a global rating of >1 . Outcome measures included BEHAVE-AD, Cohen-Mansfield Agitation Inventor}’ (CMAI), and CGI.23 Significant reductions in BEHAVE-AD total scores, psychosis, and aggressiveness subscale scores were seen in patients receiving 1 and 2 mg/day risperidone, compared with patients on placebo. Adverse events were more commonly seen in the 2 mg/day group and included extrapyramidal symptoms, somnolence, and mild peripheral edema.23 Antidepressants such as aminophylline sertraline exert their main effects via the serotonergic system. Sertraline has been evaluated for its efficacy in the treatment of depression in AD (Lyketsos C, personal communication). Twentynine patients were assessed with the Neuropsychiatrie Inventory (NPI). Average baseline scores were 7.3. After 12 weeks of treatment, patients on sertraline had a reduction in scores by 2.78 points, while the placebo group scores were increased by 0.18 points.