Progression to Dementia in Very Late‐Onset Schizophrenia‐Like Psychosis Stratified by Alzheimer's Disease and Lewy Body Disease Biomarkers: A Retrospective Cohort Study

Abstract

ABSTRACT Background Very late‐onset schizophrenia‐like psychosis (VLOSLP) is clinically heterogeneous, and its relationship with dementia‐related neurodegenerative disease remains unresolved. We examined whether Alzheimer's disease (AD) and Lewy body disease (LBD) biomarker status were associated with dementia progression in VLOSLP. Methods We retrospectively identified patients who visited the University of Osaka Hospital between January 2018 and December 2023 and met criteria for VLOSLP. Twenty‐two participants with AD and/or LBD biomarker data and at least one follow‐up assessment within 775 days were classified as biomarker‐negative (BMs‐neg; n = 7) or biomarker‐positive (BMs‐pos; n = 15). Group comparisons were performed using Mann–Whitney U tests and Fisher's exact tests. Results The BMs‐pos group showed older onset age and lower memory scores than the BMs‐neg group. Dementia progression was more frequent in the BMs‐pos group than in the BMs‐neg group, although the difference was not statistically significant (8/15 [53.3%] vs. 1/7 [14.3%]; p = 0.165; odds ratio 6.31; 95% CI 0.55–353.18). Five of eight participants with AD biomarker positivity progressed to AD dementia. Three of seven participants with LBD biomarker positivity progressed to dementia, including two diagnosed with dementia with Lewy bodies. Follow‐up MMSE, CDR, and CDR‐SB scores differed significantly between groups. Conclusions AD and/or LBD biomarker‐positive VLOSLP may be associated with greater dementia progression and cognitive decline, although findings should be interpreted cautiously given the small sample size and retrospective design. These results support the clinical value of considering neurodegenerative biomarkers when evaluating the prognosis and underlying pathology of VLOSLP.