Conversion to dementia in very late-onset schizophrenia-like psychosis classified with Alzheimer's disease and Lewy body disease biomarkers: A retrospective cohort study

Conversion to dementia in very late-onset schizophrenia-like psychosis classified with Alzheimer's disease and Lewy body disease biomarkers: A retrospective cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Short Report Conversion to dementia in very late-onset schizophrenia-like psychosis classified with Alzheimer's disease and Lewy body disease biomarkers: A retrospective cohort study Yuto Satake, Hideki Kanemoto, Daiki Taomoto, Kayo Takeda, Shigeki Katakami, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5655144/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract This study aimed to examine the conversion rate to dementia and cognitive changes in individuals with very late-onset schizophrenia-like psychosis (VLOSLP) classified with Alzheimer's disease (AD) and Lewy body disease (LBD) biomarkers. Patients with VLOSLP were retrospectively enrolled in the study, and follow-up assessments were conducted at least once up to approximately 2 years. Participants were classified into AD and LBD biomarker-negative (BMs-neg), AD-biomarker-positive and LBD biomarker-negative (AD-pos/LBD-neg), and LBD biomarker-positive (LBD-pos) groups. The conversion rate during the study period and longitudinal cognitive changes between the initial and final assessments were analyzed. Nineteen participants were enrolled in the study among patients who visited the neuropsychology clinic of the Department of Psychiatry, Osaka University Hospital, for the first time between 2018 and 2023. The conversion rates to dementia were 14%, 67%, and 50% in the BMs-neg, AD-pos/LBD-neg, and LBD-pos groups, respectively, without a significant difference (p = 0.187). At the follow-up assessment, all four participants who experienced conversion in the AD-pos/LBD-neg group were diagnosed with AD dementia, while in the LBD-pos group, two of such patients were diagnosed with dementia with Lewy bodies, and one was diagnosed with idiopathic normal pressure hydrocephalus. The only participant in the BMs-neg group converted was diagnosed with an unclassified form of dementia. Mixed-design analysis of variance revealed a significant group-by-time interaction in the Clinical Dementia Rating sum of boxes (p = 0.004). Patients with VLOSLP who are positive for AD and/or LBD biomarkers may be more likely to progress to dementia within 2 years than those who are negative. late paraphrenia late-onset schizophrenia delusional disorder Alzheimer's disease Lewy body disease dementia mild cognitive impairment biomarker Introduction The term "very late-onset schizophrenia-like psychosis" (VLOSLP) is currently used to describe a group of late-onset psychotic disorders that manifest after 60 years of age. Although the criteria define psychosis as not being explained by organic diseases or affective disorders, there is no explicit method for excluding psychosis in cases with a latent neurodegenerative disease [ 1 ]. Additionally, several reports have shown that VLOSLP is likely to cause dementia [ 2 , 3 ]. Some patients demonstrate positive results for Alzheimer's disease (AD) biomarkers [ 4 ] and Lewy body disease (LBD) biomarkers [ 5 ]. However, whether the results of the biomarkers contribute to dementia conversions. Methods Study design This retrospective observational cohort study was approved by the Ethical Review Board of Osaka University Hospital (identification number: 19117[T1]). The review board waived the requirement for written informed consent, and an opt-out procedure was implemented. All data were anonymized prior to analysis. All procedures were performed in accordance with the ethical standards of the 1964 Declaration of Helsinki and subsequent updates. Participants Study participants were enrolled from a database of consecutive patients who visited the neuropsychology clinic of the Department of Psychiatry at Osaka University Hospital for the first time between January 2018 and December 2023. The study excluded patients lacking data on the Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), and either the Neuropsychiatric Inventory (NPI) or the Brief Psychiatric Rating Scale. VLOSLP was defined according to the criteria used in our previous study, in which the absence of dementia was defined as a CDR < 1 [ 5 ]. Patients whose native language was not Japanese were excluded. Subsequently, data of patients with VLOSLP who were followed up at least once within a 2-year and 1.5-month period (equivalent to 775 days) were extracted. Participants were classified into three groups: 1) AD and LBD biomarker-negative (BMs-neg), 2) AD biomarker-positive and LBD biomarker-negative (AD-pos/LBD-neg), and 3) LBD biomarker-positive (LBD-pos). Those who did not have sufficient biomarker results to be classified into these groups and lacked CDR at follow-up were excluded from the final selection of participants. The results of the AD biomarkers (amyloid positron emission tomography and cerebrospinal fluid phosphorylated tau) and LBD biomarkers (2β-carbometoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane [FP-CIT] single photon emission computed tomography [SPECT] and metaiodobenzylguanidine myocardial scintigraphy) were collected from the initial assessments to the subsequent 3 years. The process of collecting these biomarkers is outlined in the Supplementary Note . Measures Clinical data, including demographic information, biomarker results, MMSE, Wechsler Memory Scale-Revised (WMS-R) Logical Memory (LM) I/II, and CDR, were extracted from the hospital's electronic health records. Since the clinical assessments were not necessarily conducted annually for each patient, the most recent results of the assessments carried out during the 775 days (approximately 2 years and 1.5 months) from the initial examination were considered as the follow-up assessment results. A CDR score of 1 was used to define conversion to dementia. Analyses First, we compared the demographic characteristics of the participants and other patients with VLOSLP to check the selection bias. Also, the participants' demographics at the first assessment were compared among the three groups classified with biomarker results. Thereafter, as a primary outcome, we compared the conversion rates to dementia at follow-up using Fisher’s exact test. We also compared changes in the CDR sum of boxes (CDR-SB) scores, MMSE scores, and the sum of scores of delusions and hallucinations of the NPI (NPI-psychosis) from the initial to follow-up assessments between the three groups using a mixed-model Analysis of Variance (ANOVA) with age as a covariate. Post hoc pairwise comparisons were performed with the Bonferroni correction when significant differences were found. We conducted the Kolmogorov–Smirnov test before the mixed-model ANOVA to examine the normality of the data. This study allowed missing data on scales other than the MMSE and CDR when the statistical tests were performed. All statistical analyses adopted a two-tailed p-value < 0.05 as the threshold for statistical significance and were performed using SPSS Statistics for Windows, Version 27.0. (IBM Corp., Armonk, NY, USA). A detailed chart review of psychotic symptoms and medication details was conducted in all cases. To draw graphs, we used JMP Pro 17.2.0. (SAS Institute Inc., Cary, NC, USA). Results Enrollment and Patients’ baseline characteristics From 1241 patients who visited our neuropsychological clinic between January 2018 and December 2023, we specified 67 patients with VLOSLP and enrolled 19 for this study ( Supplementary Fig. 1 ). The demographic data of participants and unenrolled patients with VLOSLP did not show any significant differences ( Supplementary Table 1 ). There were seven patients in the BMs-neg group, six in the AD-pos/LBD-neg group, and six in the LBD-pos group. The onset age and WMS-R LM scores were significantly different ( Supplementary Table 2 ). The conversion rate to dementia During the observation period, one of seven BMs-neg (14.3%) participants, four of six AD-pos/LBD-neg (66.7%) participants, and three of six LBD-pos (50%) participants showed the CDR score of one. The conversion rates were not significantly different between the groups (p = 0.187, Table 1 ). At the follow-up assessment, in the AD-pos/LBD-neg group, all four participants who experienced conversion were diagnosed with AD dementia, while in the LBD-pos group, two were diagnosed with dementia with Lewy bodies (DLB), and the other was diagnosed with possible idiopathic normal pressure hydrocephalus (iNPH). The patient who experienced conversion in the BMs-neg group was not clinically diagnosed with a particular type of dementia because her functional deficits were affected by severe apathy rather than cognitive deterioration. Table 1 The conversion rate to dementia BMs-neg (n = 7) AD-pos/LBD-neg (n = 6) LBD-pos (n = 6) Converted, n 1 (14.3%) 4 (66.7%) 3 (50.0%) Stable, n 6 (85.7%) 2 (33.3%) 3 (50.0%) Data are presented as numbers (%). “Converted” and “Stable” refer to those who experienced conversion to dementia and those who did not, respectively, during the observation period. Abbreviations: BMs-neg, biomarker-negative group; AD-pos/LBD-neg, Alzheimer’s disease biomarker-positive and Lewy body disease biomarker-negative group; LBD-pos, Lewy body disease biomarker-positive group. The longitudinal changes The mixed-design ANOVA revealed a significant group-by-time interaction in the CDR-SB scores (p = 0.004) and significant group effects in the MMSE scores (p = 0.022) (Table 2 ). Pairwise post hoc tests using Bonferroni correction showed significant differences in CDR-SB scores between the groups at the follow-up assessment (p = 0.007, Supplementary Table 3 ) and in MMSE scores between the BMs-neg and LBD-pos groups at the follow-up assessment (p = 0.006, Supplementary Table 4 ). The trend in change in MMSE scores showed a similar decline in the AD-pos/LBD-neg and LBD-pos groups and was almost stable in the BMs-neg group ( Supplementary Fig. 2 ). The CDR-SB worsened in the AD-pos/LBD-neg group, slightly worsened in the LBD-pos group, and slightly improved in the BMs-neg group. Regarding the change in the scores of the NPI-psychosis domains, the Kolmogorov–Smirnov test showed a p-value of 0.034 for the NPI-psychosis score at the second evaluation; therefore, we prepared the line graph for each group at each assessment only. The mean changes in the NPI-psychosis domains were highest in the BMs-neg group, intermediate in the AD-pos/LBD-neg group, and lowest in the LBD-pos group. Table 2 Mixed ANOVA for MMSE and CDR-SB df Sums of Squares Mean Squares F p CDR-SB Group 2 31.0 15.5 4.753 0.025 Time 1 1.6 1.6 0.977 0.339 Group*Time 2 25.9 13.0 7.923 0.004 Error 15 48.9 3.3 ˗ ˗ MMSE Group 2 71.4 35.7 4.99 0.022 Time 1 8.5 8.5 3.117 0.098 Group*Time 2 12.4 6.2 2.264 0.138 Error 15 107.3 7.2 ˗ ˗ Abbreviations: ANOVA, Analysis of Variance; df, degree of freedom; MMSE, Mini-Mental State Examination; CDR-SB, Clinical Dementia Rating-sum of boxes. Supplementary Table 5 summarizes the core features of DLB, converted dementia type, psychotic content, and medications in each case. Discussion The present study did not identify any statistically significant differences in the conversion rates to dementia among the three VLOSLP groups classified with AD and LBD biomarkers. Nevertheless, mixed ANOVA demonstrated a significant group-by-time interaction in the CDR-SB. Furthermore, the line graphs indicate that the BM-neg group exhibited stable MMSE and CDR-SB scores compared to the other two groups. Our findings indicate that positivity for AD and LBD biomarkers may serve as potential predictors for dementia conversion in patients with VLOSLP. Of the three converts in the LBD-pos group, one was diagnosed with iNPH. The participant showed a positive result in FP-CIT SPECT ( Supplementary Table 5) . While this patient may have LBD as a comorbidity, it is also possible that FP-CIT showed a false positive result for LBD. Gibson et al. reported that the core symptoms of DLB are highly reliable predictors of future DLB diagnoses in VLOSLP [ 6 ]. To predict future dementia types, it will be necessary to take into account such symptomatic characteristics along with biomarker results. This study has some limitations. First, the minimal number of participants and multiple statistical comparisons without statistical corrections could cause a large possibility of α- and β-errors, respectively. Second, as this was a retrospective study and the number of patients available for analysis was small compared to the original number of VLOSLP patients, there was a severe selection bias. Third, the timing of follow-up varied between the participants. Fourth, multiple statistical comparisons were performed without statistical corrections. In conclusion, although our study found no significant difference in the conversion rate to dementia among the three groups, the results suggest that patients with VLOSLP who were positive for AD and/or LBD biomarkers were more likely to show progressive cognitive decline within 2 years than those who were negative. Further studies with larger numbers of participants and regular longitudinal assessments are required. Glossary AD, Alzheimer's disease; CDR, Clinical Dementia Rating; iNPH, idiopathic normal pressure hydrocephalus; LBD, Lewy body disease; LM, Logical Memory; VLOSLP, very late-onset schizophrenia-like psychosis; WMS-R, Wechsler Memory Scale-Revised Declarations Funding sources This study was supported by JSPS KAKENHI Grant Number TK21K157300. Acknowledgments: We would like to thank all Neuropsychology Laboratory members of the Department of Psychiatry, Osaka University, for their helpful input regarding the data in this report and Editage ( www.editage.com ) for English language editing. References Howard R, Rabins PV, Seeman MV, Jeste DV (2000) Late-onset schizophrenia and very-late-onset schizophrenia-like psychosis: An international consensus. The International Late-Onset Schizophrenia Group. Am J Psychiatry 157:172–178. https://doi.org/10.1176/appi.ajp.157.2.172 Brodaty H, Sachdev P, Koschera A, Monk D, Cullen B (2003) Long-term outcome of late-onset schizophrenia: 5-year follow-up study. Br J Psychiatry 183:213–219. https://doi.org/10.1192/bjp.183.3.213 Stafford J, Dykxhoorn J, Sommerlad A, Dalman C, Kirkbride JB, Howard R (2023) Association between risk of dementia and very late-onset schizophrenia-like psychosis: A Swedish population-based cohort study. Psychol Med 53:750–758. https://doi.org/10.1017/S0033291721002099 Satake Y, Kanemoto H, Taomoto D, Suehiro T, Koizumi F, Sato S et al (2024) Characteristics of very late-onset schizophrenia-like psychosis classified with the biomarkers for Alzheimer's disease: A retrospective cross-sectional study. Int Psychogeriatr 36:64–77. https://doi.org/10.1017/S1041610222001132 Kanemoto H, Satake Y, Suehiro T, Taomoto D, Koizumi F, Sato S et al (2022) Characteristics of very late-onset schizophrenia-like psychosis as prodromal dementia with Lewy bodies: A cross-sectional study. Alzheimers Res Ther 14:137. https://doi.org/10.1186/s13195-022-01080-x Gibson LL, Mueller C, Stewart R, Aarsland D Characteristics associated with progression to probable dementia with Lewy bodies in a cohort with very late-onset psychosis. Psychol Med https://doi.org/10.1017/S0033291724001922 Additional Declarations The authors declare no competing interests. Supplementary Files Supplements2412162.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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study\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe term \"very late-onset schizophrenia-like psychosis\" (VLOSLP) is currently used to describe a group of late-onset psychotic disorders that manifest after 60 years of age. Although the criteria define psychosis as not being explained by organic diseases or affective disorders, there is no explicit method for excluding psychosis in cases with a latent neurodegenerative disease [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Additionally, several reports have shown that VLOSLP is likely to cause dementia [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Some patients demonstrate positive results for Alzheimer's disease (AD) biomarkers [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] and Lewy body disease (LBD) biomarkers [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, whether the results of the biomarkers contribute to dementia conversions.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003e This retrospective observational cohort study was approved by the Ethical Review Board of Osaka University Hospital (identification number: 19117[T1]). The review board waived the requirement for written informed consent, and an opt-out procedure was implemented. All data were anonymized prior to analysis. All procedures were performed in accordance with the ethical standards of the 1964 Declaration of Helsinki and subsequent updates.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eParticipants\u003c/h3\u003e\n\u003cp\u003eStudy participants were enrolled from a database of consecutive patients who visited the neuropsychology clinic of the Department of Psychiatry at Osaka University Hospital for the first time between January 2018 and December 2023. The study excluded patients lacking data on the Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), and either the Neuropsychiatric Inventory (NPI) or the Brief Psychiatric Rating Scale. VLOSLP was defined according to the criteria used in our previous study, in which the absence of dementia was defined as a CDR\u0026thinsp;\u0026lt;\u0026thinsp;1 [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Patients whose native language was not Japanese were excluded. Subsequently, data of patients with VLOSLP who were followed up at least once within a 2-year and 1.5-month period (equivalent to 775 days) were extracted. Participants were classified into three groups: 1) AD and LBD biomarker-negative (BMs-neg), 2) AD biomarker-positive and LBD biomarker-negative (AD-pos/LBD-neg), and 3) LBD biomarker-positive (LBD-pos). Those who did not have sufficient biomarker results to be classified into these groups and lacked CDR at follow-up were excluded from the final selection of participants. The results of the AD biomarkers (amyloid positron emission tomography and cerebrospinal fluid phosphorylated tau) and LBD biomarkers (2β-carbometoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane [FP-CIT] single photon emission computed tomography [SPECT] and metaiodobenzylguanidine myocardial scintigraphy) were collected from the initial assessments to the subsequent 3 years. The process of collecting these biomarkers is outlined in the \u003cb\u003eSupplementary Note\u003c/b\u003e.\u003c/p\u003e\n\u003ch3\u003eMeasures\u003c/h3\u003e\n\u003cp\u003eClinical data, including demographic information, biomarker results, MMSE, Wechsler Memory Scale-Revised (WMS-R) Logical Memory (LM) I/II, and CDR, were extracted from the hospital's electronic health records. Since the clinical assessments were not necessarily conducted annually for each patient, the most recent results of the assessments carried out during the 775 days (approximately 2 years and 1.5 months) from the initial examination were considered as the follow-up assessment results. A CDR score of 1 was used to define conversion to dementia.\u003c/p\u003e\n\u003ch3\u003eAnalyses\u003c/h3\u003e\n\u003cp\u003eFirst, we compared the demographic characteristics of the participants and other patients with VLOSLP to check the selection bias. Also, the participants' demographics at the first assessment were compared among the three groups classified with biomarker results. Thereafter, as a primary outcome, we compared the conversion rates to dementia at follow-up using Fisher\u0026rsquo;s exact test. We also compared changes in the CDR sum of boxes (CDR-SB) scores, MMSE scores, and the sum of scores of delusions and hallucinations of the NPI (NPI-psychosis) from the initial to follow-up assessments between the three groups using a mixed-model Analysis of Variance (ANOVA) with age as a covariate. Post hoc pairwise comparisons were performed with the Bonferroni correction when significant differences were found. We conducted the Kolmogorov\u0026ndash;Smirnov test before the mixed-model ANOVA to examine the normality of the data. This study allowed missing data on scales other than the MMSE and CDR when the statistical tests were performed. All statistical analyses adopted a two-tailed p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 as the threshold for statistical significance and were performed using SPSS Statistics for Windows, Version 27.0. (IBM Corp., Armonk, NY, USA). A detailed chart review of psychotic symptoms and medication details was conducted in all cases. To draw graphs, we used JMP Pro 17.2.0. (SAS Institute Inc., Cary, NC, USA).\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eEnrollment and Patients\u0026rsquo; baseline characteristics\u003c/h2\u003e \u003cp\u003eFrom 1241 patients who visited our neuropsychological clinic between January 2018 and December 2023, we specified 67 patients with VLOSLP and enrolled 19 for this study (\u003cb\u003eSupplementary Fig.\u0026nbsp;1\u003c/b\u003e). The demographic data of participants and unenrolled patients with VLOSLP did not show any significant differences (\u003cb\u003eSupplementary Table\u0026nbsp;1\u003c/b\u003e). There were seven patients in the BMs-neg group, six in the AD-pos/LBD-neg group, and six in the LBD-pos group. The onset age and WMS-R LM scores were significantly different (\u003cb\u003eSupplementary Table\u0026nbsp;2\u003c/b\u003e).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eThe conversion rate to dementia\u003c/h3\u003e\n\u003cp\u003eDuring the observation period, one of seven BMs-neg (14.3%) participants, four of six AD-pos/LBD-neg (66.7%) participants, and three of six LBD-pos (50%) participants showed the CDR score of one. The conversion rates were not significantly different between the groups (p\u0026thinsp;=\u0026thinsp;0.187, Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). At the follow-up assessment, in the AD-pos/LBD-neg group, all four participants who experienced conversion were diagnosed with AD dementia, while in the LBD-pos group, two were diagnosed with dementia with Lewy bodies (DLB), and the other was diagnosed with possible idiopathic normal pressure hydrocephalus (iNPH). The patient who experienced conversion in the BMs-neg group was not clinically diagnosed with a particular type of dementia because her functional deficits were affected by severe apathy rather than cognitive deterioration.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe conversion rate to dementia\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBMs-neg (n\u0026thinsp;=\u0026thinsp;7)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAD-pos/LBD-neg (n\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLBD-pos (n\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConverted, n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (66.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStable, n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6 (85.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are presented as numbers (%). \u0026ldquo;Converted\u0026rdquo; and \u0026ldquo;Stable\u0026rdquo; refer to those who experienced conversion to dementia and those who did not, respectively, during the observation period. Abbreviations: BMs-neg, biomarker-negative group; AD-pos/LBD-neg, Alzheimer\u0026rsquo;s disease biomarker-positive and Lewy body disease biomarker-negative group; LBD-pos, Lewy body disease biomarker-positive group.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eThe longitudinal changes\u003c/h3\u003e\n\u003cp\u003eThe mixed-design ANOVA revealed a significant group-by-time interaction in the CDR-SB scores (p\u0026thinsp;=\u0026thinsp;0.004) and significant group effects in the MMSE scores (p\u0026thinsp;=\u0026thinsp;0.022) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Pairwise post hoc tests using Bonferroni correction showed significant differences in CDR-SB scores between the groups at the follow-up assessment (p\u0026thinsp;=\u0026thinsp;0.007, \u003cb\u003eSupplementary Table\u0026nbsp;3\u003c/b\u003e) and in MMSE scores between the BMs-neg and LBD-pos groups at the follow-up assessment (p\u0026thinsp;=\u0026thinsp;0.006, \u003cb\u003eSupplementary Table\u0026nbsp;4\u003c/b\u003e). The trend in change in MMSE scores showed a similar decline in the AD-pos/LBD-neg and LBD-pos groups and was almost stable in the BMs-neg group (\u003cb\u003eSupplementary Fig.\u0026nbsp;2\u003c/b\u003e). The CDR-SB worsened in the AD-pos/LBD-neg group, slightly worsened in the LBD-pos group, and slightly improved in the BMs-neg group. Regarding the change in the scores of the NPI-psychosis domains, the Kolmogorov\u0026ndash;Smirnov test showed a p-value of 0.034 for the NPI-psychosis score at the second evaluation; therefore, we prepared the line graph for each group at each assessment only. The mean changes in the NPI-psychosis domains were highest in the BMs-neg group, intermediate in the AD-pos/LBD-neg group, and lowest in the LBD-pos group.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMixed ANOVA for MMSE and CDR-SB\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003edf\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSums of Squares\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMean Squares\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCDR-SB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e31.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e15.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.753\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.025\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTime\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.977\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.339\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGroup*Time\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e25.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e13.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.923\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.004\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eError\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e48.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e˗\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e˗\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMMSE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e71.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e35.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.022\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTime\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e8.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e8.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.117\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.098\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGroup*Time\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.264\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.138\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eError\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e107.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e˗\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e˗\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eAbbreviations: ANOVA, Analysis of Variance; df, degree of freedom; MMSE, Mini-Mental State Examination; CDR-SB, Clinical Dementia Rating-sum of boxes.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eSupplementary Table\u0026nbsp;5\u003c/b\u003e summarizes the core features of DLB, converted dementia type, psychotic content, and medications in each case.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe present study did not identify any statistically significant differences in the conversion rates to dementia among the three VLOSLP groups classified with AD and LBD biomarkers. Nevertheless, mixed ANOVA demonstrated a significant group-by-time interaction in the CDR-SB. Furthermore, the line graphs indicate that the BM-neg group exhibited stable MMSE and CDR-SB scores compared to the other two groups. Our findings indicate that positivity for AD and LBD biomarkers may serve as potential predictors for dementia conversion in patients with VLOSLP.\u003c/p\u003e \u003cp\u003eOf the three converts in the LBD-pos group, one was diagnosed with iNPH. The participant showed a positive result in FP-CIT SPECT (\u003cb\u003eSupplementary Table\u0026nbsp;5)\u003c/b\u003e. While this patient may have LBD as a comorbidity, it is also possible that FP-CIT showed a false positive result for LBD. Gibson et al. reported that the core symptoms of DLB are highly reliable predictors of future DLB diagnoses in VLOSLP [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. To predict future dementia types, it will be necessary to take into account such symptomatic characteristics along with biomarker results.\u003c/p\u003e \u003cp\u003eThis study has some limitations. First, the minimal number of participants and multiple statistical comparisons without statistical corrections could cause a large possibility of α- and β-errors, respectively. Second, as this was a retrospective study and the number of patients available for analysis was small compared to the original number of VLOSLP patients, there was a severe selection bias. Third, the timing of follow-up varied between the participants. Fourth, multiple statistical comparisons were performed without statistical corrections.\u003c/p\u003e \u003cp\u003eIn conclusion, although our study found no significant difference in the conversion rate to dementia among the three groups, the results suggest that patients with VLOSLP who were positive for AD and/or LBD biomarkers were more likely to show progressive cognitive decline within 2 years than those who were negative. Further studies with larger numbers of participants and regular longitudinal assessments are required.\u003c/p\u003e"},{"header":"Glossary","content":"\u003cp\u003eAD, Alzheimer\u0026apos;s disease; CDR, Clinical Dementia Rating; iNPH, idiopathic normal pressure hydrocephalus; LBD, Lewy body disease; LM, Logical Memory; VLOSLP, very late-onset schizophrenia-like psychosis; \u0026nbsp;WMS-R, Wechsler Memory Scale-Revised\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding sources\u003c/h2\u003e\n\u003cp\u003eThis study was supported by JSPS KAKENHI Grant Number TK21K157300.\u003c/p\u003e\n\u003ch2\u003eAcknowledgments:\u003c/h2\u003e\n\u003cp\u003eWe would like to thank all Neuropsychology Laboratory members of the Department of Psychiatry, Osaka University, for their helpful input regarding the data in this report and Editage (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ewww.editage.com\u003c/span\u003e\u003c/span\u003e) for English language editing.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHoward R, Rabins PV, Seeman MV, Jeste DV (2000) Late-onset schizophrenia and very-late-onset schizophrenia-like psychosis: An international consensus. The International Late-Onset Schizophrenia Group. Am J Psychiatry 157:172\u0026ndash;178. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1176/appi.ajp.157.2.172\u003c/span\u003e\u003cspan address=\"10.1176/appi.ajp.157.2.172\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrodaty H, Sachdev P, Koschera A, Monk D, Cullen B (2003) Long-term outcome of late-onset schizophrenia: 5-year follow-up study. Br J Psychiatry 183:213\u0026ndash;219. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1192/bjp.183.3.213\u003c/span\u003e\u003cspan address=\"10.1192/bjp.183.3.213\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStafford J, Dykxhoorn J, Sommerlad A, Dalman C, Kirkbride JB, Howard R (2023) Association between risk of dementia and very late-onset schizophrenia-like psychosis: A Swedish population-based cohort study. Psychol Med 53:750\u0026ndash;758. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1017/S0033291721002099\u003c/span\u003e\u003cspan address=\"10.1017/S0033291721002099\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSatake Y, Kanemoto H, Taomoto D, Suehiro T, Koizumi F, Sato S et al (2024) Characteristics of very late-onset schizophrenia-like psychosis classified with the biomarkers for Alzheimer's disease: A retrospective cross-sectional study. Int Psychogeriatr 36:64\u0026ndash;77. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1017/S1041610222001132\u003c/span\u003e\u003cspan address=\"10.1017/S1041610222001132\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKanemoto H, Satake Y, Suehiro T, Taomoto D, Koizumi F, Sato S et al (2022) Characteristics of very late-onset schizophrenia-like psychosis as prodromal dementia with Lewy bodies: A cross-sectional study. Alzheimers Res Ther 14:137. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/s13195-022-01080-x\u003c/span\u003e\u003cspan address=\"10.1186/s13195-022-01080-x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGibson LL, Mueller C, Stewart R, Aarsland D Characteristics associated with progression to probable dementia with Lewy bodies in a cohort with very late-onset psychosis. Psychol Med \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1017/S0033291724001922\u003c/span\u003e\u003cspan address=\"10.1017/S0033291724001922\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[{"identity":"28eb48c0-26a5-4e78-9d21-f7a32e31ea83","identifier":"10.13039/501100001691","name":"Japan Society for the Promotion of Science","awardNumber":"KAKENHI Grant Number TK21K157300","order_by":0}],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Osaka University","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"late paraphrenia, late-onset schizophrenia, delusional disorder, Alzheimer's disease, Lewy body disease, dementia, mild cognitive impairment, biomarker","lastPublishedDoi":"10.21203/rs.3.rs-5655144/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5655144/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThis study aimed to examine the conversion rate to dementia and cognitive changes in individuals with very late-onset schizophrenia-like psychosis (VLOSLP) classified with Alzheimer's disease (AD) and Lewy body disease (LBD) biomarkers. Patients with VLOSLP were retrospectively enrolled in the study, and follow-up assessments were conducted at least once up to approximately 2 years. Participants were classified into AD and LBD biomarker-negative (BMs-neg), AD-biomarker-positive and LBD biomarker-negative (AD-pos/LBD-neg), and LBD biomarker-positive (LBD-pos) groups. The conversion rate during the study period and longitudinal cognitive changes between the initial and final assessments were analyzed. Nineteen participants were enrolled in the study among patients who visited the neuropsychology clinic of the Department of Psychiatry, Osaka University Hospital, for the first time between 2018 and 2023. The conversion rates to dementia were 14%, 67%, and 50% in the BMs-neg, AD-pos/LBD-neg, and LBD-pos groups, respectively, without a significant difference (p\u0026thinsp;=\u0026thinsp;0.187). At the follow-up assessment, all four participants who experienced conversion in the AD-pos/LBD-neg group were diagnosed with AD dementia, while in the LBD-pos group, two of such patients were diagnosed with dementia with Lewy bodies, and one was diagnosed with idiopathic normal pressure hydrocephalus. The only participant in the BMs-neg group converted was diagnosed with an unclassified form of dementia. Mixed-design analysis of variance revealed a significant group-by-time interaction in the Clinical Dementia Rating sum of boxes (p\u0026thinsp;=\u0026thinsp;0.004). Patients with VLOSLP who are positive for AD and/or LBD biomarkers may be more likely to progress to dementia within 2 years than those who are negative.\u003c/p\u003e","manuscriptTitle":"Conversion to dementia in very late-onset schizophrenia-like psychosis classified with Alzheimer's disease and Lewy body disease biomarkers: A retrospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-20 04:55:17","doi":"10.21203/rs.3.rs-5655144/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e84dd574-55d7-4e24-a500-eaea691a1d61","owner":[],"postedDate":"December 20th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-12-20T04:55:17+00:00","versionOfRecord":[],"versionCreatedAt":"2024-12-20 04:55:17","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5655144","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5655144","identity":"rs-5655144","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}