Increased familial risk of the psychotic phenotype of Alzheimer disease

BACKGROUND: Psychotic symptoms in patients with AD (AD with psychosis [AD+P]) define a phenotype characterized by more rapid cognitive and functional decline and a liability to aggressive behaviors. OBJECTIVE: To determine if AD+P aggregates within families. METHODS: Case-control study of AD+P frequency in 461 siblings of 371 probands diagnosed with AD. All siblings were ascertained as part of a genetic investigation and also were diagnosed with AD. Statistical analysis used Generalized Estimating Equations to adjust for clustering within families. RESULTS: AD+P in probands was associated with a significantly increased risk for AD+P in family members (OR, 2.41; 95% CI 1.46-4.0; p = 0.0006). The correlation among siblings for AD+P status was modest: 0.16. CONCLUSION: AD+P demonstrates familial aggregation. Further studies are required to investigate a possible genetic basis of AD+P.