With Noncognitive Symptoms in

Behavioral and psychological symptoms (that is, noncog-nitive symptoms) are frequently present in patients with Alzheimer’s disease (AD). These symptoms, which include depression, euphoria, agitation, aggression, psychosis, dis-inhibition, irritability, apathy, and aberrant motor behav-ior, are a source of distress for caregivers,1 one of the main reasons for nursing home placement,2 and one of the main component of the cost of AD.3 Although noncognitive behav-ioral changes are ubiquitous in AD,4,5 the manifestation of these disturbances is highly heterogeneous across AD patients.6 Distinct genetic determinants have been hypoth-esized to be related to several noncognitive symptoms. Association between APOE allele ε4, the most important genetic risk factor for AD, and behavior abnormalities has been documented7-9; however, other studies have not found any relation.10-16 Besides APOE, other genes such as dopamine (DRD1 and DRD3) and serotonine receptors (5-HT2A and 5-HT2C) have been related to neuropsychi-atric abnormalities in AD patients.17,18 Recently, a study using a large cohort of AD patients and their siblings has showed a familial aggregation of psychotic symptoms in AD.19 These data support the hypothesis that genetic fac-tors may play a role in the manifestation of noncognitive symptoms in AD; therefore, the behavioral heterogeneity found in AD patients could be related to an individual genetic background. One crucial event in the pathological process of AD is oxidative stress.20,21 Evidences of oxidative damage in AD brains include lipid peroxidation, protein oxidation, an