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 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.

Exploring the Genetic Landscape of Mild Behavioral Impairment as an Early Marker of Cognitive Decline: An Updated Review Focusing on Alzheimer’s Disease

“…These results suggest that the APOE e4 allele might at least partially mediate the relationship between MBI and cognitive function. Another study based on the same dataset demonstrated that the relationship between psychosis and incident cognitive impairment, as assessed by the MBI-C, was modified by the APOE genotype [ 41 ]. In this study, cognitive decline was determined via the progression of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) from <3.6 at baseline to >3.6 at annual re-evaluations with a maximum follow-up of 5 years [ 41 ].…”

Schizophrenie im Alter

“…2 Merkmale der Schizophrenie [2,3,7,19,20,21,22,64]. der SCI und MCI unter den milden Verhaltensauffälligkeiten den stärksten Prädiktor einer kognitiven Verschlechterung dar [12,30]. Die Häufigkeiten psychotischer Symptome wurden bei der Lewykörperchendemenz [31] mit bis zu 75%, der Parkinsondemenz mit 50%, der Alzheimerdemenz mit 41-50%, der vaskulären Demenz mit 15%, der Chorea Huntington mit 13% und der Frontotemporalen Demenz mit 10% angegeben [12,15,32].…”

“…organischen Erkrankungen -Medikamentenänderungen -Drogengebrauch ▪ frühe medikamentöse Therapieresistenz ▶ Tab. 5 Charakteristika von psychotischen Symptomen bei Demenzerkrankungen im Vergleich zur Schizophrenie unabhängig vom Alter der Erstmanifestation [17,23,29,30,31,64].…”

Tau-PET in early cortical Alzheimer brain regions in relation to mild behavioral impairment in older adults with either normal cognition or mild cognitive impairment

“…Mild Behavioral Impairment (MBI) is a validated dementia risk syndrome (Ismail et al, 2016) distinct from chronic and/or recurrent psychiatric illness (Matsuoka et al, 2019;Taragano et al, 2018). While conventionally measured NPS are associated with incident dementia, MBI leverages neurodegenerative disease associations with later-life emergent and persistent NPS to identify a group at much higher risk (Bateman et al, 2020;Creese et al, 2023;Creese et al, 2019;Ebrahim et al, 2023;Gill et al, 2020;Gill, Sascha et al, 2021;Ismail et al, 2023a;Ismail et al, 2021;Kan et al, 2022;Matsuoka et al, 2019;McGirr, A. et al, 2022;Rouse et al, 2023;Vellone et al, 2022;Yoon et al, 2022). Several recent papers have demonstrated this point when MBI was compared to psychiatric disorders or NPS not meeting MBI criteria, with the MBI group having faster cognitive decline and progressing more rapidly to dementia (Ebrahim et al, 2023;Ghahremani, Maryam et al, 2023;Ismail et al, 2023a;Ismail et al, 2023b;Matsuoka et al, 2019;Taragano et al, 2018;Vellone et al, 2022), and even lower reversion rates from MCI to NC (McGirr, Alexander et al, 2022).…”