Association of psychosis with cognitive impairment is mediated by amyloidopathy in cognitive impairment.
| Title: | Association of psychosis with cognitive impairment is mediated by amyloidopathy in cognitive impairment. |
|---|---|
| Authors: | Pyun JM; Department of Neurology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, Seongnam, Republic of Korea.; Han S; Department of Neurology, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Republic of Korea.; Park SW; Department of Next Generation Big Data Center, Kangwon National University Hospital, Chuncheon, Republic of Korea.; Department of Neurology, Kangwon National University Hospital, Kangwon National University College of Medicine, Chuncheon, Republic of Korea.; Yeo NY; Department of Medical Bigdata Convergence, Kangwon National University, Chuncheon, Republic of Korea.; Park YH; Department of Neurology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, Seongnam, Republic of Korea.; Kim SY; Department of Neurology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, Seongnam, Republic of Korea.; Youn YC; Department of Neurology, Chung-Ang University Hospital, Seoul, Republic of Korea.; Jang JW; Department of Next Generation Big Data Center, Kangwon National University Hospital, Chuncheon, Republic of Korea. |
| Corporate Authors: | and the Alzheimer’s Disease Neuroimaging Initiative |
| Source: | Frontiers in aging neuroscience [Front Aging Neurosci] 2026 Jan 12; Vol. 17, pp. 1663120. Date of Electronic Publication: 2026 Jan 12 (Print Publication: 2025). |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Frontiers Research Foundation Country of Publication: Switzerland NLM ID: 101525824 Publication Model: eCollection Cited Medium: Print ISSN: 1663-4365 (Print) Linking ISSN: 16634365 NLM ISO Abbreviation: Front Aging Neurosci Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Original Publication: Lausanne : Frontiers Research Foundation |
| Abstract: | Background: Psychosis, including delusions and hallucinations, is a significant neuropsychiatric symptom in Alzheimer's disease (AD) associated with poor prognosis. The relationship between psychosis and AD pathology remains controversial. This study investigates the role of AD pathology in mediating the association between psychosis and cognitive impairment.; Methods: Data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We included individuals with a Clinical Dementia Rating (CDR) score of 0.5 or higher. Among a total of 833 individuals, 96 individuals with psychosis were matched to 192 individuals without psychosis using propensity scores based on age, sex, education level, and follow-up duration. Baseline cognitive performance was assessed using composite memory scores (ADNI-MEM) and executive function scores (ADNI-EF). AD pathology was measured using baseline cerebralspinal fluid (CSF) levels of β-amyloid1-42 (Aβ1-42), hyperphosphorylated-tau181 (p-tau181), and total tau. Logistic regression was performed to evaluate the association of psychosis with baseline cognitive performance and CSF biomarkers. Mediation analysis was conducted to assess whether AD biomarkers mediate the relationship between cognitive impairment and psychosis.; Results: Psychosis was significantly associated with worse ADNI MEM score (β = -0.622, p = 0.013) and worse ADNI EF score (β = -0.516, p = 0.003), and lower CSF Aβ1-42 levels (β = -0.009, p = 0.007). No significant associations were found with p-tau181 or total tau levels. Mediation analysis revealed that low CSF Aβ1-42 levels mediated the relationship between cognitive impairment and psychosis.; Conclusion: These findings suggest that amyloid pathology may mediate the effect of baseline cognitive impairment on psychosis during disease in AD, highlighting a potential pathological link between cognitive decline and psychotic symptoms.; (Copyright © 2026 Pyun, Han, Park, Yeo, Park, Kim, Youn, Jang and the Alzheimer’s Disease Neuroimaging Initiative.) |
| Competing Interests: | The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. |
| References: | J Alzheimers Dis. 2014;39(4):759-73. (PMID: 24270207); J Psychiatr Res. 1975 Nov;12(3):189-98. (PMID: 1202204); Curr Neurol Neurosci Rep. 2020 Oct 13;20(12):57. (PMID: 33048274); Br J Psychiatry. 1994 Jul;165(1):53-9. (PMID: 7953058); J Alzheimers Dis. 2024;97(1):471-484. (PMID: 38143362); Brain Imaging Behav. 2012 Dec;6(4):502-16. (PMID: 22782295); Arch Gen Psychiatry. 2000 Dec;57(12):1165-73. (PMID: 11115331); Dement Geriatr Cogn Disord. 2012;33(6):393-9. (PMID: 22814093); Am J Geriatr Psychiatry. 2018 Mar;26(3):304-313. (PMID: 29174998); Brain Imaging Behav. 2012 Dec;6(4):517-27. (PMID: 22644789); Neurology. 1994 Dec;44(12):2308-14. (PMID: 7991117); Brain. 2021 Apr 12;144(3):999-1012. (PMID: 33501939); Int Psychogeriatr. 2024 Jan;36(1):64-77. (PMID: 36714996); Neurobiol Aging. 2014 Sep;35(9):2021-8. (PMID: 24731519); Transl Psychiatry. 2022 Feb 26;12(1):82. (PMID: 35217635); Neurology. 1993 Nov;43(11):2412-4. (PMID: 8232972); Int Psychogeriatr. 2017 Feb;29(2):195-208. (PMID: 27806743); Neurology. 2000 May 23;54(10):1965-71. (PMID: 10822438); BMJ Open. 2019 Dec 18;9(12):e031947. (PMID: 31857304); Int J Geriatr Psychiatry. 2008 Feb;23(2):170-7. (PMID: 17607801); J Clin Psychiatry. 2016 Dec;77(12):e1564-e1569. (PMID: 28086011); Ann Neurol. 2009 Apr;65(4):403-13. (PMID: 19296504); Int Psychogeriatr. 2009 Feb;21(1):78-85. (PMID: 18814807); JAMA Psychiatry. 2024 Aug 1;81(8):834-839. (PMID: 38922609); Neurology. 2021 Sep 28;97(13):e1276-e1287. (PMID: 34413181); Alzheimers Dement. 2020 Jan;16(1):192-199. (PMID: 31914223); Arch Neurol. 1991 Jun;48(6):619-24. (PMID: 1710105); Alzheimer Dis Assoc Disord. 2018 Jul-Sep;32(3):185-189. (PMID: 29553944); Alzheimers Dement. 2015 Jul;11(7):734-9. (PMID: 26194309); Neurobiol Aging. 2012 Dec;33(12):2807-16. (PMID: 22429885); Front Neurol. 2012 May 07;3:73. (PMID: 22586419); Arch Neurol. 2005 Oct;62(10):1601-8. (PMID: 16216946); Am J Psychiatry. 2015 May;172(5):460-5. (PMID: 25585033); Am J Psychiatry. 2005 Nov;162(11):2022-30. (PMID: 16263838); Am J Psychiatry. 2013 Oct;170(10):1212-3. (PMID: 24084821) |
| Contributed Indexing: | Keywords: Alzheimer’s disease; amyloidopathy; cerebrospinal fluid; cognition; mediation; neurodegeneration; psychosis; tauopathy |
| Entry Date(s): | Date Created: 20260128 Date Completed: 20260128 Latest Revision: 20260131 |
| Update Code: | 20260131 |
| PubMed Central ID: | PMC12832791 |
| DOI: | 10.3389/fnagi.2025.1663120 |
| PMID: | 41601598 |
| Database: | MEDLINE |
Journal Article