title: Neuroimaging basis in the conversion of aMCI patients with APOE-ε4 to AD: study protocol of a prospective diagnostic trial.
abstract: BACKGROUND
  The ε4 allele of the Apolipoprotein E gene (APOE-ε4) is a potent genetic risk factor for sporadic Alzheimer's disease (AD). Amnestic mild cognitive impairment (aMCI) is an intermediate state between normal cognitive aging and dementia, which is easy to convert to AD dementia. It is an urgent problem in the field of cognitive neuroscience to reveal the conversion of aMCI-ε4 to AD. Based on our preliminary work, we will study the neuroimaging features in the special group of aMCI-ε4 with multi-modality magnetic resonance imaging (structural MRI, resting state-fMRI and diffusion tensor imaging) longitudinally.
  
  
  METHODS
  In this study, 200 right-handed subjects who are diagnosed as aMCI with APOE-ε4 will be recruited at the memory clinic of the Neurology Department, XuanWu Hospital, Capital Medical University, Beijing, China. All subjects will undergo the neuroimaging and neuropsychological evaluation at a 1 year-interval for 3 years. The primary outcome measures are 1) Microstructural alterations revealed with multimodal MRI scans including structure MRI (sMRI), resting state functional MRI (rs-fMRI), diffusion tensor imaging (DTI); 2) neuropsychological evaluation, including the World Health Organization-University of California-LosAngeles Auditory Verbal Learning Test (WHO-UCLA AVLT), Addenbrook's cognitive examination-revised (ACE-R), mini-mental state examination (MMSE), Montreal Cognitive Assessment (MoCA), Clinical Dementia Rating scale (CDR).
  
  
  CONCLUSIONS
  This study is to find out the neuroimaging biomarker and the changing laws of the marker during the progress of aMCI-ε4 to AD, and the final purpose is to provide scientific evidence for new prevention, diagnosis and treatment of AD.
  
  
  BACKGROUND
  This study has been registered to ClinicalTrials.gov (NCT02225964, https://www.clinicaltrials.gov/ ) in August 24, 2014.
authors.affiliation: Department of Neurology, XuanWu Hospital of Capital Medical University, Beijing, 100053, China.
authors.forename: Guan-Qun
authors.initials: GQ
authors.lastname: Chen
authors.affiliation: Department of Neurology, XuanWu Hospital of Capital Medical University, Beijing, 100053, China.
authors.forename: Can
authors.initials: C
authors.lastname: Sheng
authors.affiliation: Department of Neurology, XuanWu Hospital of Capital Medical University, Beijing, 100053, China.|Department of Neurology, Tangshan Gongren Hospital, Tangshan, 063000, China.
authors.forename: Yu-Xia
authors.initials: YX
authors.lastname: Li
authors.affiliation: Department of Neurology, XuanWu Hospital of Capital Medical University, Beijing, 100053, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Neurology, XuanWu Hospital of Capital Medical University, Beijing, 100053, China.
authors.forename: Xiao-Ni
authors.initials: XN
authors.lastname: Wang
authors.affiliation: Department of Neurology, XuanWu Hospital of Capital Medical University, Beijing, 100053, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Neurology, XuanWu Hospital of Capital Medical University, Beijing, 100053, China.|Department of Neurology, Civil Aviation General Hospital, Beijing, 100123, China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Li
authors.affiliation: Department of Neurology, XuanWu Hospital of Capital Medical University, Beijing, 100053, China.
authors.forename: Xuan-Yu
authors.initials: XY
authors.lastname: Li
authors.affiliation: Department of Neurology, XuanWu Hospital of Capital Medical University, Beijing, 100053, China.
authors.forename: Yun-Yan
authors.initials: YY
authors.lastname: Xie
authors.affiliation: Department of Neurology, XuanWu Hospital of Capital Medical University, Beijing, 100053, China. hanying@xwh.ccmu.edu.cn.|Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, 100053, China. hanying@xwh.ccmu.edu.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Han
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000235:genetics / Q000523:psychology; D053327:Apolipoprotein E4 / Q000235:genetics; D015415:Biomarkers; D002681:China; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging* / Q000235:genetics / Q000523:psychology; D056324:Diffusion Tensor Imaging / Q000379:methods; D018450:Disease Progression; D005500:Follow-Up Studies; D059907:Functional Neuroimaging; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D009483:Neuropsychological Tests; D011446:Prospective Studies
chemical_list: D053327:Apolipoprotein E4; D015415:Biomarkers
keywords: APOE4 allele; Alzheimer’s disease; Amnestic mild cognitive impairment; Longitudinal study; Multimodality; Neuroimaging techniques