Prediction of Psychosis in Alzheimer Disease

Psychotic symptoms, defined as the occurrence of delusions or hallucinations, are frequent in Alzheimer disease (AD with psychosis, AD+P), affecting ~ 40% to 60% of individuals with AD. AD+P identifies a subgroup of AD patients with poor outcomes. The strongest clinical predictor of AD+P is a greater degree of cognitive impairment than in AD subjects without psychosis (AD- P). Although the estimated heritability of psychosis in AD is 61%, the underlying genetic sources of this risk is not known.

We conducted a genome-wide meta-analysis of 12,317 probable, possible, or autopsy-confirmed AD subjects, each of whom were characterized to be negative or positive for psychosis. The presence of psychosis was defined by the occurrence of delusions and/or hallucinations as assessed by standardized rating scales (see published manuscript for the details of the psychosis assessments in each contributing study program). The absence of psychosis required individuals to have no symptoms of psychosis at all evaluations and additionally to have progressed past the early stage of AD. This latter criterion was operationalized as a mini-mental state exam score =<20 or a clinical dementia rating scale score >=1.