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

Abstract

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 was rated using the Mild Behavioral Impairment Checklist (henceforth MBI-psychosis). The whole sample was analyzed before stratification on APOE-ε4 status. RESULTS: In Cox proportional hazards models, MBI-psychosis had a higher hazard for cognitive impairment relative to the No Psychosis group (hazard ratio (HR):3.6, 95% CI:2.2-11 6, p<0.0001). The hazard for MBI-psychosis was higher in APOE-ε4 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.