Behavioral outcomes in clinical trials for Alzheimer disease.

The use of behavioral scales is an important component in determining efficacy of new drugs in clinical trials for Alzheimer disease (AD). Behavioral assessment in clinical trials must be sensitive to disease heterogeneity, disease progression, and drug modification of behavior. Three such scales, the Behavior Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD), the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Behavior Rating Scale for Dementia (C-BRSD), and the Cohen-Mansfield Agitation Inventory (CMAI), are useful in clinical trials. The BEHAVE-AD reliably assesses the severity of a range of AD symptoms (7 areas with 25 items) and rates behavioral impact on caregivers. The C-BRSD enables reliable assessment of the frequency of behaviors (8 areas with 48 items) in AD and monitors relevant behaviors throughout the course of the disease. However, it does not assess the impact of behaviors on caregivers. The CMAI focuses on assessment of agitation and aggression and is compatible with C-BRSD but does not assess the impact of agitation on caregivers. A recent trial evaluated the C-BRSD and the CMAI in more than 300 AD and normal elderly individuals. Both of these scales discriminated between AD and non-AD patients, were sensitive across disease severity, and could track behavioral changes over 12 months of AD progression. The BEHAVE-AD, C-BRSD, and CMAI scales are valid, reliable, rapid to administer, cover relevant behaviors occurring during the course of the disease, and are appropriate for use in AD clinical trials.