Longitudinal Multi-modal Imaging in Progressive Supranuclear Palsy Syndromes

进行性核上性麻痹综合征的纵向多模态成像

• 批准号: 10683769
• 负责人: Keith A Josephs
• 金额: $ 78.45万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-15 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10683769
• 关键词: Address; Anatomy; Apraxias; Atrophic; Autopsy; Behavior; Behavioral; Biological Markers; Brain; Brain Stem; Brain imaging; Brain region; Characteristics; Classification; Clinical; Data; Deglutition Disorders; Deposition; Development; Diagnosis; Diffusion Magnetic Resonance Imaging; Disease; Disease Progression; Evaluation; Evolution; Exhibits; Freezing; Future; Gait; Goals; Grant; Heterogeneity; Impairment; Knowledge; Language; Ligands; Limb structure; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Modality; Modeling; Monitor; Movement Disorders; Multimodal Imaging; Nerve Degeneration; Neurobiology; Neurodegenerative Disorders; Neurologic; Parkinsonian Disorders; Pathologic; Pathology; Patient Recruitments; Patients; Pattern; Positron-Emission Tomography; Progressive Supranuclear Palsy; Proteins; Publishing; Research; Research Personnel; Societies; Speech; Standardization; Symptoms; Syndrome; Time; Variant; Work; brain tissue; experience; falls; gaze palsy; improved; indexing; interest; multimodal neuroimaging; multimodality; neural; neurobiological mechanism; neuroimaging; neuropathology; oculomotor; posture instability; prognostic; rate of change; recruit; research study; tau Proteins; tau mutation; treatment effect; treatment trial; uptake; white matter

PROJECT SUMMARY Progressive supranuclear palsy (PSP) is a devastating neurodegenerative disorder that is characterized by deposition of the protein 4-repeat (4R) tau in the brain. Patients typically present with postural instability with falls, axial rigidity and vertical supranuclear gaze palsy, although other atypical clinical syndromes occur in which patients present with parkinsonism, freezing of gait, behavioral abnormalities, limb apraxia or speech and language difficulties. In the 1st cycle of the R01 we characterized the cross-sectional and longitudinal behavior of the tau-PET ligand [18F]AV-1451 in PSP and showed that it is related to other neuroimaging measures of neurodegeneration. The 1st cycle focused on the typical clinical presentation of PSP. Since the 1st cycle, a panel of leading experts published new criteria with a standard to diagnose the atypical clinical syndromes. We currently lack understanding of the neurobiology of the atypical PSP syndromes. The primary goal of the 2nd cycle is, therefore, to characterize the clinical, neuroimaging and neuropathological features across typical and atypical PSP syndromes. Specifically, we aim to characterize the cross- sectional and longitudinal multi-modal neuroimaging signatures of the PSP syndromes, determine the relationship between neuroimaging and clinical evolution, and evaluate the autopsy characteristics of the PSP syndromes. We will have data from 160 PSP patients to allow us to address our aims (84 recruited into the 1st cycle and 76 which will be recruited in the 2nd cycle). Each newly recruited patient will undergo the identical examinations as the 84 patients from the 1st cycle, including a neurological and dysphagia evaluation, a 3T magnetic resonance imaging (MRI) that includes structural MRI and diffusion tensor imaging (DTI), and tau- PET using the [18F]AV-1451 ligand. All patients will undergo two serial assessments one year apart. We will assess differences and commonalities in all three neuroimaging modalities across PSP syndromes primarily using a focused region-of-interest approach which will target key brainstem, subcortical and cortical regions that are involved in PSP. We will then ascertain whether the PSP syndromes exhibit unique multi-modal signatures using a classification model. Voxel-level analyses will also be performed to assess patterns across the whole brain. The relationship between clinical evolution, including the evolution of dysphagia, and the PSP syndromes and neuroimaging measures will be assessed. Autopsy examinations will be performed on all patients from both cycles that die and 4R tau burden will be compared across PSP syndromes. We will also determine the degree to which neuroimaging differences across syndromes are related to tau burden and investigate how additional pathologies are associated with the different syndromes. The results of this grant will increase our knowledge of the neural underpinnings of the clinical and anatomical heterogeneity in PSP and will also be essential for the development of optimum biomarkers for PSP that will aid diagnosis, track disease progression and allow patients with all PSP syndromes to be included in future treatment trials.

项目总结

项目成果

Longitudinal clinical decline and baseline predictors in progressive supranuclear palsy.

进行性核上性麻痹的纵向临床衰退和基线预测因素。

• DOI: 10.1016/j.parkreldis.2023.105290
• 发表时间: 2023
• 期刊: Parkinsonism & related disorders
• 影响因子: 4.1
• 作者: Pavone,Costanza;Weigand,StephenW;Ali,Farwa;Clark,HeatherM;Botha,Hugo;Machulda,MaryM;Savica,Rodolfo;Pham,NhaTrangThu;Grijalva,RosalieM;Schwarz,ChristopherG;Senjem,MatthewL;Agosta,Federica;Filippi,Massimo;Jack,CliffordR

Sensitivity-Specificity of Tau and Amyloid β Positron Emission Tomography in Frontotemporal Lobar Degeneration.

tau和淀粉样β正电子发射断层扫描的敏感性特异性。

• DOI: 10.1002/ana.25893
• 发表时间: 2020-11
• 期刊: Annals of neurology
• 影响因子: 11.2
• 作者: Ghirelli A;Tosakulwong N;Weigand SD;Clark HM;Ali F;Botha H;Duffy JR;Utianski RL;Buciuc M;Murray ME;Labuzan SA;Spychalla AJ;Pham NTT;Schwarz CG;Senjem ML;Machulda MM;Baker M;Rademakers R;Filippi M;Jack CR Jr;Lowe VJ;Parisi JE;Dickson DW;Josephs KA;Whitwell JL
• 通讯作者: Whitwell JL

Longitudinal Amyloid-β PET in Atypical Alzheimer's Disease and Frontotemporal Lobar Degeneration.

纵向淀粉样蛋白-β PET 在非典型阿尔茨海默病和额颞叶变性中的应用。

• DOI: 10.3233/jad-190699
• 发表时间: 2020
• 期刊: Journal of Alzheimer's disease : JAD
• 作者: Whitwell,JenniferL;Tosakulwong,Nirubol;Weigand,StephenD;Graff-Radford,Jonathan;Duffy,JosephR;Clark,HeatherM;Machulda,MaryM;Botha,Hugo;Utianski,ReneL;Schwarz,ChristopherG;Senjem,MatthewL;Strand,EdytheA;Ertekin-Taner,Nilufe
• 通讯作者: Ertekin-Taner,Nilufe

Influences of motor speech impairments on the presentation of dysphagia in progressive supranuclear palsy.

运动性言语障碍对进行性核上性麻痹吞咽困难表现的影响。

• DOI: 10.1080/17549507.2023.2221407
• 发表时间: 2024
• 期刊: International journal of speech-language pathology
• 影响因子: 1.8
• 作者: Petroi-Bock,Diana;Clark,HeatherM;Stierwalt,JulieAG;Botha,Hugo;Ali,Farwa;Whitwell,JenniferL;Josephs,KeithA
• 通讯作者: Josephs,KeithA

Longitudinal changes in dopamine transporter uptake scans in progressive apraxia of speech.

• DOI: 10.1016/j.prdoa.2023.100207
• 发表时间: 2023
• 期刊: CLINICAL PARKINSONISM & RELATED DISORDERS
• 作者: Utianski, Rene L.;Pham, Nha Trang Thu;Botha, Hugo;Ali, Farwa;Duffy, Joseph R.;Clark, Heather M.;Lowe, Val J.;Whitwell, Jennifer L.;Josephs, Keith A.
• 通讯作者: Josephs, Keith A.