Clinical utility of cerebrospinal fluid Alzheimer’s disease biomarkers in the diagnostic workup of complex patients with cognitive impairment

Abstract Cerebrospinal fluid (CSF) biomarkers have been widely adopted in Alzheimer’s disease (AD) diagnosis. However, no studies focused on the application of CSF biomarkers in the clinical practice of complex and atypical patients with cognitive impairment in China. This study aimed to evaluate th...

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Main Authors: Ming-Yu Wang, Ke-Liang Chen, Yu-Yuan Huang, Shu-Fen Chen, Rong-Ze Wang, Yi Zhang, He-Ying Hu, Ling-Zhi Ma, Wei-Shi Liu, Jun Wang, Jia-Wei Xin, Xue Zhang, Meng-Meng Li, Yu Guo, Qiang Dong, Wei Cheng, Lan Tan, Mei Cui, Ya-Ru Zhang, Jin-Tai Yu
Format: Article
Language:English
Published: Nature Publishing Group 2025-04-01
Series:Translational Psychiatry
Online Access:https://doi.org/10.1038/s41398-025-03345-z
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author Ming-Yu Wang
Ke-Liang Chen
Yu-Yuan Huang
Shu-Fen Chen
Rong-Ze Wang
Yi Zhang
He-Ying Hu
Ling-Zhi Ma
Wei-Shi Liu
Jun Wang
Jia-Wei Xin
Xue Zhang
Meng-Meng Li
Yu Guo
Qiang Dong
Wei Cheng
Lan Tan
Mei Cui
Ya-Ru Zhang
Jin-Tai Yu
author_facet Ming-Yu Wang
Ke-Liang Chen
Yu-Yuan Huang
Shu-Fen Chen
Rong-Ze Wang
Yi Zhang
He-Ying Hu
Ling-Zhi Ma
Wei-Shi Liu
Jun Wang
Jia-Wei Xin
Xue Zhang
Meng-Meng Li
Yu Guo
Qiang Dong
Wei Cheng
Lan Tan
Mei Cui
Ya-Ru Zhang
Jin-Tai Yu
author_sort Ming-Yu Wang
collection DOAJ
description Abstract Cerebrospinal fluid (CSF) biomarkers have been widely adopted in Alzheimer’s disease (AD) diagnosis. However, no studies focused on the application of CSF biomarkers in the clinical practice of complex and atypical patients with cognitive impairment in China. This study aimed to evaluate the added value of CSF AD biomarkers in cognitively impaired patients with complex conditions in a memory clinical setting. A total of 633 participants were included from the National Center for Neurological Disorders in Shanghai, China. The CSF AD biomarkers were measured with ELISA. Cutoff values were firstly identified using Youden’s index. The neurologists proposed etiology diagnosis with a percentage estimate of their confidence and prescribed medication before and after CSF disclosure. Changes in etiological diagnosis, diagnostic confidence, and management plan were compared across the groups. Of the 633 patients (mean [SD] age, 61.1 [11.3] years; 295 males [46.6%]), 372 (58.8%) were diagnosed with dementia, 103 (16.3%) with mild cognitive impairment, and 158 (24.9%) with subjective cognitive decline. Using those pre-defined cutoffs, we categorized patients into 3 groups: Alzheimer’s continuum (68.1%), non-AD pathologic change (11.1%), and normal AD biomarkers (20.8%). After CSF disclosure, the proposed etiology changed in 158 (25.0%) participants and the prescribed medication changed in 200 (31.6%) patients. Mean diagnostic confidence increased from 69.5–83.0% (+13.5%; P < 0.001). In conclusion, CSF AD biomarkers significantly impacted the diagnosis, diagnostic confidence, and treatment plans for Chinese patients with complex cognitive impairment. CSF AD biomarkers are a useful tool for clinicians beyond routine clinical assessment.
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spelling doaj-art-1e1a0960243e4e78a22fac5bf583e2462025-08-20T03:10:14ZengNature Publishing GroupTranslational Psychiatry2158-31882025-04-0115111010.1038/s41398-025-03345-zClinical utility of cerebrospinal fluid Alzheimer’s disease biomarkers in the diagnostic workup of complex patients with cognitive impairmentMing-Yu Wang0Ke-Liang Chen1Yu-Yuan Huang2Shu-Fen Chen3Rong-Ze Wang4Yi Zhang5He-Ying Hu6Ling-Zhi Ma7Wei-Shi Liu8Jun Wang9Jia-Wei Xin10Xue Zhang11Meng-Meng Li12Yu Guo13Qiang Dong14Wei Cheng15Lan Tan16Mei Cui17Ya-Ru Zhang18Jin-Tai Yu19Department of Neurology, Qingdao Municipal Hospital, Qingdao UniversityDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan UniversityDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan UniversityDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan UniversityDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan UniversityDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan UniversityDepartment of Neurology, Qingdao Municipal Hospital, Qingdao UniversityDepartment of Neurology, Qingdao Municipal Hospital, Qingdao UniversityDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan UniversityDepartment of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical UniversityDepartment of Neurology, Fujian Institute of Geriatrics, Fujian Medical University Union HospitalDepartment of Neurology, Qingdao Central Hospital, University of Health and Rehabilitation SciencesDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan UniversityDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan UniversityDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan UniversityDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan UniversityDepartment of Neurology, Qingdao Municipal Hospital, Qingdao UniversityDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan UniversityDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan UniversityDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan UniversityAbstract Cerebrospinal fluid (CSF) biomarkers have been widely adopted in Alzheimer’s disease (AD) diagnosis. However, no studies focused on the application of CSF biomarkers in the clinical practice of complex and atypical patients with cognitive impairment in China. This study aimed to evaluate the added value of CSF AD biomarkers in cognitively impaired patients with complex conditions in a memory clinical setting. A total of 633 participants were included from the National Center for Neurological Disorders in Shanghai, China. The CSF AD biomarkers were measured with ELISA. Cutoff values were firstly identified using Youden’s index. The neurologists proposed etiology diagnosis with a percentage estimate of their confidence and prescribed medication before and after CSF disclosure. Changes in etiological diagnosis, diagnostic confidence, and management plan were compared across the groups. Of the 633 patients (mean [SD] age, 61.1 [11.3] years; 295 males [46.6%]), 372 (58.8%) were diagnosed with dementia, 103 (16.3%) with mild cognitive impairment, and 158 (24.9%) with subjective cognitive decline. Using those pre-defined cutoffs, we categorized patients into 3 groups: Alzheimer’s continuum (68.1%), non-AD pathologic change (11.1%), and normal AD biomarkers (20.8%). After CSF disclosure, the proposed etiology changed in 158 (25.0%) participants and the prescribed medication changed in 200 (31.6%) patients. Mean diagnostic confidence increased from 69.5–83.0% (+13.5%; P < 0.001). In conclusion, CSF AD biomarkers significantly impacted the diagnosis, diagnostic confidence, and treatment plans for Chinese patients with complex cognitive impairment. CSF AD biomarkers are a useful tool for clinicians beyond routine clinical assessment.https://doi.org/10.1038/s41398-025-03345-z
spellingShingle Ming-Yu Wang
Ke-Liang Chen
Yu-Yuan Huang
Shu-Fen Chen
Rong-Ze Wang
Yi Zhang
He-Ying Hu
Ling-Zhi Ma
Wei-Shi Liu
Jun Wang
Jia-Wei Xin
Xue Zhang
Meng-Meng Li
Yu Guo
Qiang Dong
Wei Cheng
Lan Tan
Mei Cui
Ya-Ru Zhang
Jin-Tai Yu
Clinical utility of cerebrospinal fluid Alzheimer’s disease biomarkers in the diagnostic workup of complex patients with cognitive impairment
Translational Psychiatry
title Clinical utility of cerebrospinal fluid Alzheimer’s disease biomarkers in the diagnostic workup of complex patients with cognitive impairment
title_full Clinical utility of cerebrospinal fluid Alzheimer’s disease biomarkers in the diagnostic workup of complex patients with cognitive impairment
title_fullStr Clinical utility of cerebrospinal fluid Alzheimer’s disease biomarkers in the diagnostic workup of complex patients with cognitive impairment
title_full_unstemmed Clinical utility of cerebrospinal fluid Alzheimer’s disease biomarkers in the diagnostic workup of complex patients with cognitive impairment
title_short Clinical utility of cerebrospinal fluid Alzheimer’s disease biomarkers in the diagnostic workup of complex patients with cognitive impairment
title_sort clinical utility of cerebrospinal fluid alzheimer s disease biomarkers in the diagnostic workup of complex patients with cognitive impairment
url https://doi.org/10.1038/s41398-025-03345-z
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