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Progress in blood biomarkers of subjective cognitive decline in preclinical Alzheimer’s disease

Chinese Medical Journal 2023年第5期136卷 505-521页

作者： Xianfeng Yu Kai Shao Ke Wan Taoran Li Yuxia Li Xiaoqun Zhu Ying Han Department of Neurology Xuanwu Hospital of Capital Medical UniversityBeijing 100053China Department of Neurology The First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230022China Department of Neurology Tangshan Central HospitalTangshanHebei 063000China School of Biomedical Engineering Hainan UniversityHaikouHainan 570228China Center of Alzheimer’s Disease Beijing Institute for Brain DisordersBeijing 100053China National Clinical Research Center for Geriatric Diseases Beijing 100053China.

Alzheimer's disease(AD)is a neurodegenerative disease that gradually impairs cognitive ***,there has been a conceptual shift toward AD to view the disease as a *** AD is currently incurable,effective intervention to delay or prevent pathological cognitive decline may best target the early stages of symptomatic disease,such as subjective cognitive decline(SCD),in which cognitive function remains relatively *** methods for identifying AD,such as cerebrospinal fluid biomarkers and positron emission tomography,are invasive and ***,it is imperative to develop blood biomarkers that are sensitive,less invasive,easier to access,and more cost effective for AD *** review aimed to summarize the current data on whether individuals with SCD differ reliably and effectively in subjective and objective performances compared to cognitively normal elderly individuals,and to find one or more convenient and accessible blood biomarkers so that researchers can identify SCD patients with preclinical AD in the population as soon as *** to the heterogeneity and complicated pathogenesis of AD,it is difficult to make reliable diagnoses using only a single blood *** review provides an overview of the progress achieved to date with the use of SCD blood biomarkers in patients with preclinical AD,highlighting the key areas of application and current challenges.

关键词： Alzheimer’s disease Biomarker Blood Evolving technologies subjective cognitive decline

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The compensatory phenomenon of the functional connectome related to pathological biomarkers in individuals with subjective cognitive decline

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Translational Neurodegeneration 2020年第2期9卷 234-247页

作者： Haifeng Chen Xiaoning Sheng Caimei Luo Ruomeng Qin Qing Ye Hui Zhao Yun Xu Feng Bai 无 Department of Neurology Drum Tower HospitalMedical School and The State Key Laboratory of Pharmaceutical BiotechnologyInstitute of Brain ScienceNanjing University321 Zhongshan RoadNanjingJiangsu210008P.R.China Jiangsu Key Laboratory of Molecular Medicine Medical School of Nanjing UniversityNanjingChina Jiangsu Province Stroke Center for Diagnosis and Therapy NanjingChina Nanjing Neuropsychiatry Clinic Medical Center NanjingChina for the Alzheimer’s Disease Neuroimaging Initiative

Background subjective cognitive decline(SCD)is a preclinical stage along the Alzheimer’s disease(AD)***,little is known about the aberrant patterns of connectivity and topological alterations of the brain functional connectome and their diagnostic value in *** Resting-state functional magnetic resonance imaging and graph theory analyses were used to investigate the alterations of the functional connectome in 66 SCD individuals and 64 healthy controls(HC).Pearson correlation analysis was computed to assess the relationships among network metrics,neuropsychological performance and pathological ***,we used the multiple kernel learning-support vector machine(MKL-SVM)to differentiate the SCD and HC *** SCD individuals showed higher nodal topological properties(including nodal strength,nodal global efficiency and nodal local efficiency)associated with amyloid-βlevels and memory function than the HC,and these regions were mainly located in the default mode network(DMN).Moreover,increased local and medium-range connectivity mainly between the bilateral parahippocampal gyrus(PHG)and other DMN-related regions was found in SCD individuals compared with HC *** aberrant functional network measures exhibited good classification performance in the differentiation of SCD individuals from HC individuals at an accuracy up to 79.23%.Conclusion The findings of this study provide insight into the compensatory mechanism of the functional connectome underlying *** proposed classification method highlights the potential of connectome-based metrics for the identification of the preclinical stage of AD.

关键词： subjective cognitive decline rs-fMRI Machine learning Compensatory mechanism

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Hippocampal resting-state functional connectivity with the mPFC and DLPFC moderates and mediates the association between education level and memory function in subjective cognitive decline

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Brain Science Advances 2021年第2期7卷 124-140页

作者： Shurui Xu Qianqian Sun Ming Li Jia Luo Guiyan Cai Ruilin Chen Lin Zhang Jiao Liu National-Local Joint Engineering Research Center of Rehabilitation Medicine Technology Fujian University of Traditional Chinese MedicineFuzhou 350122FujianChina Affiliated Rehabilitation Hospital Fujian University of Traditional Chinese MedicineFuzhou 350122FujianChina College of Rehabilitation Medicine Fujian University of Traditional Chinese MedicineFuzhou 350122FujianChina Institute for Stroke and Dementia Research(ISD) Klinikum der UniversitätMünchenLudwig-Maximilians-Universität(LMU)MünchenMunich 81377Germany Fujian Key Laboratory of Rehabilitation Technology Fuzhou 350122FujianChina Traditional Chinese Medicine Rehabilitation Research Center of State Administration of Traditional Chinese Medicine Fujian University of Traditional Chinese MedicineFuzhou 350122FujianChina Key Laboratory of Orthopedics&Traumatology of Traditional Chinese Medicine and Rehabilitation Ministry of EducationFujian University of Traditional Chinese MedicineFuzhou 350122FujianChina

Objective:This study aims to determine the relationship between education level,memory function,and hippocampus functional and structural alterations in subjective cognitive decline(SCD).Methods:Seventy-five participants with SCD were divided into high education(HE)and low education(LE)level groups.A Wechsler Memory Scale-Chinese Revision test and functional and structural MRI were performed within 1 week after participant *** bilateral hippocampus resting-state functional connectivity(rsF C),gray matter volume(GMV)of brain regions identified by rsF C analysis,and moderating and mediating effects were ***:Compared with the LE group,HE individuals showed 1)higher memory quotient(MQ)and Digit Span subscore,2)decreased hippocampal rs FC with the right medial prefrontal cortex(mPFC)and dorsolateral prefrontal cortex(DLPFC),and 3)increased GMV in the right mP FC and *** bilateral hippocampus-right DLPFCrs FC significantly associated with the MQ and the bilateral hippocampus-right m PFCrs FC with the Digit Span subscore in each *** bilateral hippocampus-right DLPFCrsFC moderated the relationship between the education level and *** bilateral hippocampus-right mP FC rsF C mediated the relationship between the education level and Digit Span subscore in all ***:The hippocampal rsF C with the right mP FC and DLPFC contributes to the education level effect on memory function in SCD.

关键词： education level memory function resting-state functional connectivity subjective cognitive decline

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Optimizing Alzheimer’s Disease Therapy Using a Neural Intelligent Agent-Based Platform

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International Journal of Intelligence Science 2021年第2期11卷 70-96页

作者： Hamdi Ben Abdessalem Alexie Byrns Claude Frasson Département d’Informatique et de Recherche Opérationnelle Université de Montréal Montréal Canada

Alzheimer’s disease affects millions of persons every year. Negative emotions such as stress and frustration have a negative impact on memory function and Alzheimer's patients experience more negative emotions than healthy adults. Non-pharmacological treatment such as immersion in virtual environments could help Alzheimer patients by reducing their negative emotions, but it has restrictions and requirements. In this work, we present three virtual reality relaxing systems in which the patients are immersed in relaxing environments. We propose to use intelligent agents in order to adapt the relaxing environment to each participant and optimize its relaxation effect. The intelligent agents track the emotions of patients using electroencephalography as input in order to adapt the environments. We designed each system with different levels of intelligence in order to analyze the impact of the adaptation on the patients. Experiments were performed for each system on participants with subjective cognitive decline. Results show that these relaxing systems can reduce negative emotions and improve participants’ memory performance. The positive effects on affective state and memory persisted for a longer period of time and were generally more effective for the systems with more intelligence. We believe that the combination of a relaxing environment, virtual reality, intelligent agents for adapting

关键词： EEG Brain Assessment Intelligent Agent Virtual Reality Alzheimer’s Disease subjective cognitive decline Emotions Adaptation Emotional Intelligence

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Computerized cognitive Training in Healthy Older Adults:Baseline cognitive Level and subjective cognitive Concerns Predict Training Outcome

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Health 2018年第1期10卷 20-55页

作者： Elke Kalbe Christophe Bintener Anja Ophey Christian Reuter Stefan Gobel Silvie Kloters Gisela Baller Josef Kessler Department of Medical Psychology/Neuropsychology and Gender Studies&Center for Neuropsychological Diagnostics and Intervention(CeNDI) University Hospital CologneCologneGermany Institute of Gerontology Department of Psychological GerontologyUniversity of VechtaVechtaGermany Multimedia Communications Lab-KOM Technische Universitat DarmstadtDarmstadtGermany Department of Neurology University Hospital CologneCologneGermany

Computerized cognitive training (CCT) can improve cognition in older adults. However, specific programs for this target group have rarely been developed, and predictors of training success are largely unclear. In a randomized controlled pilot trial, we examined effects of a six-week CCT, tailored to the cognitive profile of healthy older adults (EG, n = 21) as compared to a nonspecific CCT (CG, n = 18) matched in frequency and intensity. No interaction effects between Group and Time were found. However, within-group analysis showed significant gains in verbal and non-verbal memory, executive and visuospatial functions and subjective cognitive concerns (SCC) in the EG, while the CG only benefitted in non-verbal memory and set-shifting. Low cognitive performance and lower SCC at baseline were the most consistent predictors of cognitive gains in the EG. Thus, CCTs specifically tailored to older adults seem advantageous compared to non-specific CCT. Further, we conclude that SCC may be related to reduced cognitive plasticity.

关键词： Computerized cognitive Training Older Adults subjective cognitive decline Psychoeducation Predictors

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Effects of the rs1799986 Polymorphism of the LRP1 Gene on the Default Mode Network among Individuals in Preclinical and Prodromal Stage of Alzheimer's Disease

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神经药理学报 2019年第4期 48-48页

作者： ZANG Fei-fei ZHU Yao ZHANG Qian-qian TAN Chang XIE Chun-ming Alzheimer's Disease Neuroimaging Initiative Department of Neurology Affiliated ZhongDa HospitalSchool of MedicineSoutheast University Data in present study were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database

Objective:The low-density lipoprotein receptor-related protein 1( LRP1) as the receptor of apolipoprotein E,plays a critical role in the clearance of Amyloidβ-peptide. The present study aims to explore the effects of the LRP1 gene rs1799986 variant on the default mode network( DMN) among subjects from subjective cognitive decline( SCD) to mild cognitive impairment( MCI) and eventually to Alzheimer’s disease( AD). Methods:Twenty-six AD subjects,42 MCI subjects,45 SCD subjects,and 55 cognitively normal controls( CN) from Alzheimer’s Disease Neuroimaging Initiative( ADNI) database were included in this study. Restingstate functional MRI scans and neuropsychological assessments were collected at baseline. Grouplevel independent component analysis( ICA) was used to obtain the DMN patterns. Multivariate linear regression analysis was employed to measure the effects of gene,disease and gene×disease on the default mode network. Results:The LRP1 gene×disease interaction for four-group subjects was mainly detected in the bilateral middle frontal gyrus( bMFG),posterior cingulate cortex( PCC) as well as retrosplenial cortex( RSC). While,the brain areas such as left temporoparietal joint( TPJ),inferior parietal cortex( IPC),PCC and RSC represent the main effect of disease,and left middle frontal gyrus( lMFG) and PCC were responsible for the main effect of LRP1 gene. Furthermore,the Z-transformed mean functional connectivity( FC) of the interactive PCC region was correlated with the Z-transformation score of mini-mental state examination( MMSE) among non-normal subjects. Conclusion:The LRP1 gene could consistently affect the DMN patterns among individuals in preclinical and prodromal stage of Alzheimer’s disease.

关键词： Alzheimer’s disease low-density lipoprotein receptor related protein 1 LRP1 default mode network subjective cognitive decline mild cognitive impairment DMN ADNI

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