Rapidly Progressive Dementia: Moving Beyond CJD

快速进展性痴呆：超越克雅氏病

• 批准号: 10569540
• 负责人: GREGORY SCOTT DAY
• 金额: $ 15.72万
• 依托单位: MAYO CLINIC JACKSONVILLE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10569540
• 关键词: Acceleration; Active Learning; Address; Affect; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease patient; Alzheimer' s disease related dementia; Alzheimer’s disease biomarker; Amyloid beta-42; Autoantibodies; Autoimmune; Autoimmune encephalitis; Autopsy; Biological; Biological Markers; Cell Count; Cerebrospinal Fluid; Chitinase; Classification; Clinical; Clinical Research; Cognition; Consensus; Counseling; Creutzfeldt-Jakob Syndrome; Dementia; Detection; Development; Diagnosis; Diagnostic; Disease; Early identification; Enrollment; Ensure; Etiology; Evaluation; Functional disorder; Future; Gender; Goals; Image; Individual; Interview; Investigation; Knowledge; Legal patent; Lewy Bodies; Light; Longitudinal Studies; Measures; Memory; Mentored Patient-Oriented Research Career Development Award; Mentors; Methodology; Neurodegenerative Disorders; Neurologic Examination; Neurologist; Neuronal Injury; Neuropsychological Tests; Observational Study; Oligoclonal Bands; Outcome; Participant; Pathologic; Pathology; Patient-Focused Outcomes; Patients; Performance; Phenotype; Positioning Attribute; Proteins; Rare Diseases; Research; Research Personnel; Resources; Serum; Severities; Signs and Symptoms; Societies; Source; Specialist; Standardization; Symptoms; Synapses; Testing; Therapeutic Trials; Universities; Vascular Dementia; Visit; Washington; accurate diagnosis; biomarker signature; cohort; diagnostic criteria; diagnostic strategy; diagnostic value; experience; functional disability; improved; improved outcome; in vivo; inflammatory marker; medical schools; mixed dementia; neurocognitive test; neurofilament; neurogranin; neuroimaging; neuroinflammation; neuron loss; neuropathology; novel therapeutics; participant enrollment; patient oriented; patient oriented research; prospective; rapid diagnosis; research clinical testing; skills; synaptosomal-associated protein 25; tau Proteins

Project Summary / Abstract Patients with rapidly progressive dementia (RPD) account for 3-4% of dementia cases, with the majority attributed to Creutzfeldt-Jakob disease (CJD), Alzheimer disease (AD) or AD-related dementias (ADRD). More recently, recognition of autoimmune encephalitis (AE) as a cause of RPD has catalyzed the development of diagnostic approaches that emphasize the need for expeditious detection of patients with eminently treatable autoimmune causes of RPD. However, remarkable overlap in the presenting clinical features and results of investigations often confounds the etiologic diagnoses of RPD, contributing to diagnostic delays, missed opportunities for treatment and poorer outcomes. There is a critical need to determine the clinical features and biological signatures that define patients with specific causes of RPD, and to develop quantifiable biomarkers that reflect disease pathology, predict progression and inform the contributions of neuronal loss, neuroinflammation and synaptic dysfunction to rates of symptomatic decline. This project will address these needs by systematically defining the clinical features, results of investigations (including serum and cerebrospinal fluid tests [CSF], and neuroimaging), and biofluid biomarker signatures that define patients with RPD due to AD, ADRD and AE. Consensus etiologic diagnoses will be established following independent review of available clinical information by multiple neurologists (Aim 1). Biomarkers of AD neuropathology, neuronal injury, neuroinflammation and synaptic dysfunction will be measured in CSF obtained at presentation from RPD patients, and from age- and gender-similar individuals with typically progressive AD and ADRD enrolled in parallel studies of memory and aging at Washington University School of Medicine (WUSM). The results of this study will define the clinical features and CSF biomarkers that differentiate patients with RPD due to AD, ADRD and AE (Aim 2A), facilitating early identification of patients with eminently treatable autoimmune causes of RPD (Aim 2B). By defining the clinical and CSF biomarker profiles that distinguish individuals with rapid and typically progressive AD and ADRD, study results will also inform the contributions of AD neuropathology, neuronal injury, neuroinflammation and synaptic dysfunction to the phenotypic expression of AD and ADRD (Aim 3). Although this project will focus on patients with RPD, study findings and experience will inform the assessment and diagnosis of all dementia patients, aiding in the identification of mechanisms that affect rates of symptomatic decline and patient outcomes. These mechanisms may be targeted through future therapeutic trials, with the goal of improving outcomes in patients with rapid and typically progressive dementia. Dr. Day will acquire necessary skills in patient-oriented research through didactic and experiential learning completed at WUSM and the affiliated Knight Alzheimer Disease Research Center, and will benefit from the support of well established experts/mentors in patient-oriented dementia research and biofluid biomarker measures, including Drs. John C Morris, Anne M Fagan, Beau M Ances and Michael D Geschwind.

项目摘要/摘要

项目成果

A Neurologist's Practical Approach to Cognitive Impairment.

• DOI: 10.1055/s-0041-1726354
• 发表时间: 2021-12
• 期刊: Seminars in neurology
• 影响因子: 2.7
• 作者: Tipton PW;Day GS;Graff-Radford N
• 通讯作者: Graff-Radford N

Ovarian resection in anti-N-methyl-D-aspartate receptor encephalitis: A comparison of surgical approaches.

• DOI: 10.3389/fneur.2022.1043785
• 发表时间: 2022
• 期刊: FRONTIERS IN NEUROLOGY
• 影响因子: 3.4
• 作者: Iyengar, Yajur;Hebert, Julien;Climans, Seth A.;Muccilli, Alexandra;Lee, Sydney;Boruah, Abhilasha P.;Thakur, Kiran T.;Solnik, Jonathon;Wennberg, Richard A.;Day, Gregory S.;Tang-Wai, David F.
• 通讯作者: Tang-Wai, David F.

Three cases of Creutzfeldt-Jakob disease presenting with a predominant dysexecutive syndrome.

• DOI: 10.1007/s00415-022-11045-7
• 发表时间: 2022-08
• 期刊: Journal of neurology
• 影响因子: 6
• 作者: Corriveau-Lecavalier N;Li W;Ramanan VK;Drubach DA;Day GS;Jones DT
• 通讯作者: Jones DT

Analysis of Clinical Features, Diagnostic Tests, and Biomarkers in Patients With Suspected Creutzfeldt-Jakob Disease, 2014-2021.

• DOI: 10.1001/jamanetworkopen.2022.25098
• 发表时间: 2022-08-01
• 期刊: JAMA NETWORK OPEN
• 影响因子: 13.8
• 作者: Shir, Dror;Lazar, Evelyn B.;Graff-Radford, Jonathan;Aksamit, Allen J.;Cutsforth-Gregory, Jeremy K.;Jones, David T.;Botha, Hugo;Ramanan, Vijay K.;Prusinski, Christian;Porter, Amanda;Day, Gregory S.
• 通讯作者: Day, Gregory S.

Deciphering the contributions of neuroinflammation to neurodegeneration: lessons from antibody-mediated encephalitis and coronavirus disease 2019.

• DOI: 10.1097/wco.0000000000001033
• 发表时间: 2022-04-01
• 期刊: Current opinion in neurology
• 影响因子: 4.8
• 作者: Shir D;Day GS
• 通讯作者: Day GS