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Late-life onset psychotic symptoms and incident cognitive impairment in people without dementia: modification by genetic risk for Alzheimer disease

INTRODUCTION: Late-life onset psychosis is associated with faster progression to dementia in cognitively normal people, but little is known about its relationship to cognitive impairment in advance of dementia. METHODS: Clinical and genetic data from 2,750 people over 50 without dementia were analyzed. Incident cognitive impairment was operationalized using the IQCODE and psychosis (MBI-psychosis) was rated using the Mild Behavioral Impairment Checklist. The whole sample was analyzed before stratification on APOE-{varepsilon}4 status. RESULTS: In Cox proportional hazards models, MBI-psychosis had a higher hazard rate (HR) for cognitive impairment relative to the No Psychosis group (HR:3.6, 95% CI:2.2-6, p<0.0001). The HR for MBI-psychosis was higher in APOE-{varepsilon}4 carriers and there was an interaction between the two (HR for interaction: 3.4, 95% CI:1.2-9.8, p=0.02). DISCUSSION: Psychosis assessment in the MBI framework is associated with incident cognitive impairment in advance of dementia, these symptoms may be particularly important in the context of APOE genotype.