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Development of machine learning-based models to predict 10-year risk of cardiovascular disease:a prospective cohort study

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Stroke & Vascular Neurology 2023年第6期8卷 475-485页

作者： Jia You yu Guo Ju-Jiao Kang Hui-Fu Wang Ming Yang Jian-Feng Feng jin-tai yu Wei Cheng Institute of Science and Technology for Brain-Inspired Intelligence Department of NeurologyHuashan HospitalState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceFudan UniversityShanghaiChina Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence Fudan UniversityMinistry of EducationShanghaiChina Zhangjiang Fudan International Innovation Center Fudan UniversityShanghaiChina School of Data Science Fudan UniversityShanghaiChina Fudan ISTBI-ZJNU Algorithm Centre for Brain-inspired Intelligence Zhejiang Normal UniversityZhejiangChina Shanghai Medical College and Zhongshan Hospital Immunotherapy Technology Transfer Center Fudan UniversityShanghaiChina

Background Previous prediction algorithms for cardiovascular diseases(CVD)were established using risk factors retrieved largely based on empirical clinical *** study sought to identify predictors among a comprehensive variable space,and then employ machine learning(ML)algorithms to develop a novel CVD risk prediction *** From a longitudinal population-based cohort of UK Biobank,this study included 473611 CVD-free participants aged between 37 and 73 years *** implemented an ML-based data-driven pipeline to identify predictors from 645 candidate variables covering a comprehensive range of health-related factors and assessed multiple ML classifiers to establish a risk prediction model on 10-year incident *** model was validated through a leave-one center-out *** During a median follow-up of 12.2 years,31466 participants developed CVD within 10 years after baseline visits.A novel UK Biobank CVD risk prediction(UKCRP)model was established that comprised 10 predictors including age,sex,medication of cholesterol and blood pressure,cholesterol ratio(total/high-density lipoprotein),systolic blood pressure,previous angina or heart disease,number of medications taken,cystatin C,chest pain and pack-years of *** model obtained satisfied discriminative performance with an area under the receiver operating characteristic curve(AUC)of 0.762±0.010 that outperformed multiple existing clinical models,and it was well-calibrated with a Brier Score of 0.057±***,the UKCRP can obtain comparable performance for myocardial infarction(AUC 0.774±0.011)and ischaemic stroke(AUC 0.730±0.020),but inferior performance for haemorrhagic stroke(AUC 0.644±0.026).Conclusion ML-based classification models can learn expressive representations from potential high-risked CVD participants who may benefit from earlier clinical decisions.

关键词： cardiovascular prediction learning

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Association of Polygenic Risk Score with Age at Onset and Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease in a Chinese Cohort

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Neuroscience Bulletin 2020年第7期36卷 696-704页

作者： Wei-Wei Li Zhen Wang Dong-yu Fan Ying-Ying Shen Dong-Wan Chen Hui-yun Li Ling Li Heng Yang yu-Hui Liu Xian-Le Bu Wang-Sheng jin Fan Zeng Zhi-Qiang Xu jin-tai yu Li-Yong Chen Yan-Jiang Wang Department of Neurology and Centre for Clinical Neuroscience Duping HospitalThird Military Medical UniversityChongqing 400042China Department of Anaesthesiology Daping HospitalThird Military Medical UniversityChongqing 400042China Chongqing Key Laboratory of Aging and Diseases Chongqing 400042China Centre for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghai 200031China Department of Neurology Huashan HospitalFudan UniversityShanghai 200040China

To evaluate whether the polygenic profile modifies the development of sporadic Alzheimer’s disease(sAD)and pathological biomarkers in cerebrospinal fluid(CSF),462 sAD patients and 463 age-matched cognitively normal(CN)controls were genotyped for 35 singlenucleotide polymorphisms(SNPs)that are significantly associated with ***,the alleles found to be associated with sAD were used to build polygenic risk score(PRS)models to represent the genetic *** operating characteristic(ROC)analyses and the Cox proportional hazards model were used to evaluate the predictive value of PRS for the sAD risk and age at *** measured the CSF levels of Aβ42,Aβ42/Aβ40,total tau(T-tau),and phosphorylated tau(P-tau)in a subgroup(60 sAD and 200 CN participants),and analyzed their relationships with the *** found that 14 SNPs,including SNPs in the APOE,BIN1,CD33,EPHA1,SORL1,and TOMM40 genes,were associated with sAD risk in our *** PRS models built with these SNPs showed potential for discriminating sAD patients from CN controls,and were able to predict the incidence rate of sAD and age at ***,the PRSs were correlated with the CSF levels of Aβ42,Aβ42/Aβ40,T-tau,and *** study suggests that PRS models hold promise for assessing the genetic risk and development of *** genetic risk profiles vary among populations,large-scale genome-wide sequencing studies are urgently needed to identify the genetic risk loci of sAD in Chinese populations to build accurate PRS models for clinical practice.

关键词： Alzheimer's disease Single nucleotide polymorphism Polygenic risk score Cerebrospinal fluid Biomarker Amyloid-beta Tau

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Voxel-based meta-analysis of grey matter changes in Alzheimer’s disease

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Translational Neurodegeneration 2015年第1期4卷 39-47页

作者： Wen-Ying Wang jin-tai yu Yong Liu Rui-Hua Yin Hui-Fu Wang Jun Wang Lin Tan Joaquim Radua Lan Tan Department of Neurology Qingdao Municipal HospitalSchool of MedicineQingdao UniversityNo.5 Donghai Middle RoadQingdaoShandong Province 266071China College of Medicine and Pharmaceutics Ocean University of ChinaQingdao 266011China Department of Neurology Qingdao Municipal HospitalNanjing Medical UniversityNanjing 266071China Brainnetome Center Institute of AutomationChinese Academy of SciencesBeijing 100190China National Laboratory of Pattern Recognition Institute of AutomationChinese Academy of SciencesBeijing 100190China Department of Psychosis Studies Institute of PsychiatryKing’s College LondonLondonUK Research Unit FIDMAG Germanes Hospitala’ries—CIBERSAMSant Boi de LlobregatBarcelonaSpain

Background:Voxel-based morphometry(VBM)using structural brain MRI has been widely used for the assessment of impairment in Alzheimer’s disease(AD),but previous studies in VBM studies on AD remain ***:We conducted meta-analyses to integrate the reported studies to determine the consistent grey matter alterations in AD based on VBM ***:The PubMed,ISI Web of Science,EMBASE and Medline database were searched for articles between 1995 and June *** searches were also conducted,and authors of studies were contacted for additional *** were extracted from clusters with significant grey matter difference between AD patients and healthy controls(HC).Meta-analysis was performed using a new improved voxel-based meta-analytic method,Effect Size Signed Differential Mapping(ES-SDM).Results:Thirty data-sets comprising 960 subjects with AD and 1195 HC met inclusion *** matter volume(GMV)reduction at 334 coordinates in AD and no GMV increase were found in the current *** reductions in GMV were robustly localized in the limbic regions(left parahippocampl gyrus and left posterior cingulate gyrus).In addition,there were GM decreases in right fusiform gyrus and right superior frontal *** findings remain largely unchanged in the jackknife sensitivity ***:Our meta-analysis clearly identified GMV atrophy in *** findings confirm that the most prominent and replicable structural abnormalities in AD are in the limbic regions and contributes to the understanding of pathophysiology underlying AD.

关键词： Voxel-based morphometry(VBM) Alzheimer’s disease(AD) Grey matter(GM) Meta-analysis Magnetic resonance imaging(MRI) Effect size signed differential mapping(ES-SDM)

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TREM in Alzheimer's Disease: Genetics, Mechanisms and Therapy

TREM in Alzheimer's Disease: Genetics, Mechanisms and Therap...

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中国神经科学学会第十二届全国学术会议

作者： Lan Tan jin-tai yu Department of Neurology Qingdao Municipal Hospital Qingdao University

Triggering receptor expressed on myeloid cells(TREMs) receptors constitute a family modulator in human innate immunity system that encode by a gene cluster, including TREM1、TREM2、TLT-1 and TLT-2. Two recent studies have identified that a rare coding variant(p. R47 H) in exon 2 of TREM2 gene increases susceptibility to lateonset Alzheimer’s disease(LOAD) with an odds ratio similar to that of the apolipoprotein E ε4 allele in Caucasian population, suggesing TREM2 represents an important susceptibility gene for LOAD. We then resequenced all exons of TREM2 and provided the first evidence that a rare coding variant(p.H157 Y) in TREM2 exon 3 conferred a considerable risk of AD with an odds ratio of 11.01. Furthermore, we decipher the expression and biologic functions of TREM2 under AD context. We showed that TREM2 was upregulated in microglia during disease progression. By knockdown and overexpression of TREM2 in cultured primary microglia, we revealed that TREM2 modulated microglial functions under AD context, as it facilitated Aβ(1-42) phagocytosis and inhibited Aβ(1-42)-triggered proinflammatory responses. Besides, TREM2 overexpression rescued spatial cognitive impairments and ameliorated neuropathologies by suppressing neuroinflammation and subsequently attenuating tau kinase activity. For the first time, we declare the crucial role of TREM2 in AD pathogenesis. More importantly, overexpression of TREM2 in the brain of APPswe/PS1 d E9 mice/P301 S mice markedly ameliorated AD-related neuropathology including Aβ deposition, tau hyperphosphorylation, neuroinflammation, neuronal and synaptic losses. These findings provide insights into the role of TREM2 in AD pathogenesis, and highlight TREM2 as a novel potential therapeutic target for this disease. At the same time, rs6910730, an intronic variant of TREM1, is associated with an increased Aβ neuropathology in the brains of elderly subjects. We further provided evidence that rs6910730 reduced the ability of human monocytes

关键词： Alzheimer’s disease TREM1 TREM2 Rare variant Aβ Tau phosphorylation Therapeutic target

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Cerebrospinal fluid α-synuclein predicts neurodegeneration and clinical progression in non-demented elders

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Translational Neurodegeneration 2020年第4期9卷 525-534页

作者： Jie-Qiong Li Yan-Lin Bi Xue-Ning Shen Hui-Fu Wang Wei Xu Chen-Chen Tan Qiang Dong Yan-Jiang Wang Lan Tan jin-tai yu 无 Department of Neurology and Institute of Neurology Huashan HospitalShanghai Medical CollegeFudan UniversityShanghai 20040China Department of Neurology Qingdao Municipal HospitalQingdao UniversityQingdao 266071China Department of Neurology The Affiliated Hospital of Qingdao UniversityQingdao 266071China Department of Anesthesiology Qingdao Municipal HospitalQingdao UniversityQingdao 266071China Department of Neurology and Center for Clinical Neuroscience Daping HospitalThird Military Medical UniversityChongqing 400042China Alzheimer's Disease Neuroimaging Initiative

Background:Accumulating reports have suggested that α-synuclein is involved in the pathogenesis of Alzheimer's disease(AD).As the cerebrospinal fluid(CSF)α-synuclein has been suggested as a potential biomarker of AD,this study was set out to test whether CSF α-synuclein is associated with other AD biomarkers and could predict neurodegeneration and clinical progression in non-demented ***:The associations between CSF a-synuclein and other AD biomarkers were investigated at baseline in non-demented Chinese *** predictive values of CSF a-synuclein for longitudinal neuroimaging change and the conversion risk of non-demented elders were assessed using linear mixed effects models and multivariate Cox proportional hazard models,respectively,in the Alzheimer's disease Neuroimaging Initiative(ADNI)***:The CSF α-synuclein levels correlated with AD-specific biomarkers,CSF total tau and phosphorylated tau levels,in 651 Chinese Han participants(training set).These positive correlations were replicated in the ADNI database(validation set).Using a longitudinal cohort from ADNI,the CSF α-synuclein concentrations were found to increase with disease *** CSF α-synuclein had high diagnostic accuracy for AD based on the"ATN"(amyloid,tau,neurodegeneration)system(A+T+versus A-T-control)(area under the receiver operating characteristic curve,0.84).Moreover,CSF α-synuclein predicted longitudinal hippocampus atrophy and conversion from MCI to AD ***:CSF α-synuclein is associated with CSF tau levels and could predict neurodegeneration and clinical progression in non-demented *** finding indicates that CSF α-synuclein is a potentially useful early biomarker for AD.

关键词： Alzheimer's disease α-Synuclein Biomarker Cerebrospinal fluid Neurodegeneration

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Longitudinal associations of cardiovascular health and vascular events with incident dementia

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Stroke & Vascular Neurology 2024年第4期9卷 418-428,I0066-I0130页

作者： Ya-Nan Ou Kevin Kuo Liu Yang Ya-Ru Zhang Shu-Yi Huang Shi-Dong Chen yue-Ting Deng yu Guo Rui-Qi Zhang Bang-Sheng Wu Lan Tan Qiang Dong Jian-Feng Feng Wei Cheng jin-tai yu Department of Neurology Qingdao Municipal HospitalQingdao UniversityQingdaoShandongPeople's Republic of China Department of Neurology and National Center for Neurological Disorders Huashan HospitalState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceShanghai Medical CollegeFudan UniversityShanghaiPeople's Republic of China Institute of Science and Technology for Brain-inspired Intelligence Fudan UniversityShanghaiPeople's Republic of China Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence Fudan UniversityMinistry of EducationShanghaiPeople's Republic of China

Introduction Evidence supporting cardiovascular diseases could increase the risk of dementia remains fragmented.A comprehensive study to illuminate the distinctive associations across different dementia types is still *** study is sought to:(1)determine the clinical validity of Framingham General Cardiovascular Risk Score(FGCRS)for dementia assessment and(2)examine the associations between cardiovascular diseases and the risk of *** A total of 432079 dementia-free individuals at baseline from UK Biobank were *** Cox proportional hazard models were used to investigate the prospective associations for FGCRS and a series of cardiovascular diseases with all-cause dementia(ACD)and its major components,Alzheimer’s disease(AD)and vascular dementia(VaD).Results During a median follow-up of 110.1 months,4711 individuals were diagnosed with *** was associated with increased risks across the dementia *** stratification analysis,high-risk groups have demonstrated the greatest dementia burdens,particularly to *** 74 traits,9 adverse associations,such as chronic ischaemic heart disease(ACD:HR=1.354;AD:HR=1.269;VaD:HR=1.768),atrioventricular block(ACD:HR=1.562;AD:HR=1.556;VaD:HR=2.069),heart failure(ACD:HR=1.639;AD:HR=1.543;VaD:HR=2.141)and hypotension(ACD:HR=2.912;AD:HR=2.361;VaD:HR=3.315)were *** distinctions were also found,with atrial fibrillation,cerebral infarction,and haemorrhage only associated with greater risks of ACD and *** By identifying distinctive associations between cardiovascular diseases and dementia,this study has established a comprehensive‘mapping’that may untangle the long-standing *** has demonstrated its predictivity beyond cardiovascular diseases burdens,suggesting potential opportunities for implantation.

关键词： cardiovascular diseases supporting

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Plasma neurofilament light as a longitudinal biomarker of neurodegeneration in Alzheimer’s disease

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Brain Science Advances 2019年第2期5卷 94-105页

作者： Ya-Nan Ou Hao Hu Zuo-Teng Wang Wei Xu Lan Tan jin-tai yu 无 Department of Neurology Qingdao Municipal HospitalQingdao UniversityQingdao 266071ShandongChina College of Medicine and Pharmaceutics Ocean University of ChinaQingdao 266100ShandongChina Department of Neurology and Institute of Neurology Huashan HospitalShanghai Medical CollegeFudan UniversityShanghai 200433China Alzheimer’s Disease Neuroimaging Initiative

Objective:To examine whether plasma neurofilament light(NFL)might be a potential longitudinal biomarker for Alzheimer’s disease(AD).Methods:A total of 835 individuals from the Alzheimer’s Disease Neuroimaging Initiative were *** of the rate of change in plasma NFL with cerebrospinal fluid biomarkers,cognition,and brain structure were *** proportional hazards models were used to assess the associations between quartiles of plasma NFL and the risk of AD ***:Participants were further divided intoβamyloid-positive(Aβ+)versusβamyloid-negative(Aβ-),resulting in five biomarker group combinations,which are CN Aβ-,CN Aβ+,MCI Aβ-,MCI Aβ+and AD Aβ+.Plasma NFL concentration markedly increased in the five groups longitudinally(p<0.001)with the greatest rate of change in AD Aβ+*** rate of change in plasma NFL was associated with cognitive deficits and neuroimaging hallmarks of AD over time(p<0.005).Compared with the bottom quartile,the top quartile of change rate was associated with a 5.41-fold increased risk of AD(95%CI=1.83-16.01)in the multivariate ***:Our finding implies the potential of plasma NFL as a longitudinal noninvasive biomarker in AD.

关键词： Alzheimer’s disease plasma neurofilament light(NFL) longitudinal neurodegeneration

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Cerebrospinal fluid heart fatty acid-binding protein as a predictive biomarker of neurodegeneration in Alzheimer's disease

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Brain Science Advances 2021年第1期7卷 44-55,1-5页

作者： Lu Pan Ya-Nan Ou Lin Tan Lan Tan jin-tai yu Alzheimer’s Disease Neuroimaging Initiative Department of Neurology Qingdao Municipal HospitalDalian Medical UniversityDalian 116044LiaoningChina Department of Neurology Qingdao Municipal HospitalQingdao UniversityQingdao 266071ShandongChina Department of Neurology and Institute of Neurology Huashan HospitalShanghai Medical CollegeFudan UniversityShanghai 200040China 不详

Objective:This study aims to investigate whether the heart fatty acid-binding protein(HFABP)in the cerebrospinal fluid(CSF)was a potential predictive biomarker for Alzheimer’s disease(AD).Methods:We evaluated the associations of CSF HFABP levels with core biomarkers,cognition,and brain structure in a sample population(n=302)from the Alzheimer’s Disease Neuroimaging Initiative(ADNI)*** linear regression and mixed-effects models were employed in the *** progression was assessed using the Kaplan–Meier survival ***:CSF HFABP was higher in patients with mild cognitive impairment and AD than the normal controls(p<0.001)and was particularly higher in those with amyloid-β(Aβ)pathologic *** HFABP was associated with higher baseline CSF t-tau(p<0.001),CSF p-tau(p<0.001),and CSF t-tau/Aβ42 and CSF p-tau/Aβ42(p<0.01).Moreover,CSF HFABP was found to play predictive roles in hippocampal atrophy(p<0.01),cognitive decline(p<0.05),and the risk of AD(p<0.001).Conclusion:Our findings suggest that CSF HFABP can be a predictive biomarker of AD.

关键词： Alzheimer’s disease heart fatty acid-binding protein(HFABP) cerebrospinal fluid biomarker neurodegeneration

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