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

Byron Creese; Ryan Arathimos; Dag Aarsland; Clive Ballard; Helen Brooker; Adam Hampshire; Anne Corbett; Zahinoor Ismail

doi:10.1002/trc2.12386

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

Alzheimers Dement (N Y). 2023 Apr 30;9(2):e12386. doi: 10.1002/trc2.12386. eCollection 2023 Apr-Jun.

Authors

Byron Creese¹, Ryan Arathimos², Dag Aarsland^{3

4}, Clive Ballard¹, Helen Brooker⁵, Adam Hampshire⁶, Anne Corbett⁷, Zahinoor Ismail^{8

9}

Affiliations

¹ Department of Clinical and Biomedical Sciences Faculty of Health and Life Sciences University of Exeter Exeter UK.
² Social Genetic and Developmental Psychiatry Centre Institute of Psychiatry, Psychology and Neuroscience King's College London London UK.
³ Department of Old Age Psychiatry Institute of Psychiatry Psychology and Neuroscience King's College London London UK.
⁴ Centre for Age-Related Medicine Stavanger University Hospital Stavanger Norway.
⁵ Department of Health and Community Sciences Faculty of Health and Life Sciences University of Exeter Exeter UK.
⁶ Department of Brain Sciences Faculty of Medicine Imperial College London London UK.
⁷ Department of Health and Community Sciences Faculty of Health and Life Sciences University of Exeter UK.
⁸ Departments of Psychiatry Clinical Neurosciences, and Community Health Sciences Hotchkiss Brain Institute and O'Brien Institute for Public Health University of Calgary Calgary Alberta Canada.
⁹ Department of Health and Community Sciences, Faculty of Health and Life Sciences University of Exeter Exeter UK.

Abstract

Introduction: Late-life onset psychosis is associated with faster progression to dementia in cognitively normal people, but little is known about its relationship with cognitive impairment in advance of dementia.

Methods: Clinical and genetic data from 2750 people ≥50 years of age without dementia were analyzed. Incident cognitive impairment was operationalized using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) and psychosis was rated using the Mild Behavioral Impairment Checklist (henceforth MBI-psychosis). The whole sample was analyzed before stratification on apolipoprotein E (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% confidence interval [CI]: 2.2-6, 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.

Keywords: APOE; cognition; mild behavioral impairment; neuropsychiatric symptoms; psychosis.