Pre-psychosis in later life as a risk factor for progressive cognitive decline: Findings from the IPA psychosis in neurodegenerative disease working group

Abstract

Pre-clinical Alzheimer’s disease (AD) has traditionally been characterized by subtle cognitive deficits alongside biomarker changes. However, emerging evidence suggests a spectrum of neuropsychiatric changes, including apathy, affective disturbances, agitation, impulse control deficits, and psychosis, may precede cognitive decline. Late-onset psychotic disorders, such as Very Late-Onset Schizophrenia-Like Psychosis (VLOSLP), differ from pre-psychosis, the latter presenting with subtle symptoms and retained insight. These subtler late-life onset symptoms are associated with incident cognitive decline, particularly in APOE4 carriers. Screening with tools such as the Mild Behavioral Impairment Checklist (MBI-C) enables the standardisation of measurement, facilitating identification of at-risk individuals. Plasma biomarkers and neuropsychological assessments further aid diagnosis and risk stratification. Understanding the link between pre-psychosis and dementia-related psychosis will be crucial, as AD with psychosis is associated with a more aggressive disease course. Identifying and treating these individuals early may improve clinical outcomes and facilitate timely intervention with disease-modifying therapies. Moreover, there remains a need to better define in what circumstances treatment interventions are indicated and what those interventions should be.