Neurophysiological Changes in Pre-clinical Alzheimer's Disease

临床前阿尔茨海默病的神经生理学变化

• 批准号: 10570248
• 负责人: Hannes Devos
• 金额: $ 13.1万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10570248
• 关键词: Adult; Aging; Alzheimer' s Disease; Amyloid; Back; Behavioral; Brain; Brain imaging; Burn injury; Clinical; Clinical Research; Clinical Sciences; Clinical Trials Design; Cognitive; Cohort Studies; Complex; Control Groups; Data; Deterioration; Development; Development Plans; Diagnosis; Disease; Early Diagnosis; Elderly; Electroencephalography; Environment; Event-Related Potentials; Evoked Potentials; Exhibits; Faculty; Foundations; Funding; Future; Goals; Grant; Hippocampus; Impaired cognition; Impairment; Individual; Kansas; Knowledge; Learning; Magnetic Resonance Imaging; Measures; Medical center; Mentored Research Scientist Development Award; Mentors; Mentorship; Metabolic; Methods; Molecular; Nerve Degeneration; Neuropsychological Tests; Neuropsychology; Normal Range; P300 Event-Related Potentials; Parkinson Disease; Patients; Performance; Physical Rehabilitation; Physical therapy; Physiological; Positron-Emission Tomography; Postdoctoral Fellow; Prevention trial; Process; Productivity; Property; Psychometrics; Research; Research Personnel; Research Project Grants; Research Scientist Award; Research Training; Resources; Risk; Severities; Short-Term Memory; Statistical Data Interpretation; System; Testing; Training; Translational Research; United States National Institutes of Health; Universities; Workload; attentional control; brain volume; career; career development; cognitive change; cognitive task; cohort; coping; experience; follow-up; functional decline; healthy aging; imaging facilities; mild cognitive impairment; multidisciplinary; neural recruitment; neuroimaging; neurophysiology; normal aging; pre-clinical; rehabilitation science; response; skills; tenure track

ABSTRACT This is a resubmission for a K01 Mentored Research Scientist Award for Dr. Hannes Devos, an Early Career, Tenure Track Faculty of Physical Therapy and Rehabilitation Science at the University of Kansas Medical Center. While I have received clinical research training in my postdoctoral years, I seek to expand my scientific foundation in becoming an independent researcher in applied neurophysiology of Alzheimer's disease (AD). My primary goal is to attain independence, capable of leading a multidisciplinary group in investigating neurophysiological markers —event-related potentials (ERP), heartbeat-evoked potentials (HEP), and task- evoked pupillary response (TEPR)— of early neurodegenerative decline in pre-clinical AD. I am at a critical point in my career to make this transition after gaining initial experience with pupillometry in Parkinson's disease. Thus, I am proposing a career development plan in which I will train with renowned experts in clinical methods (Dr. Burns), neurophysiology (Dr. Gustafson), neuro-imaging (Dr. Brooks and Dr. Burns), and research independence (Dr. Burns, Dr. Brooks, and Dr. Mahnken). From these experts' mentoring I will learn: (1) Expertise in clinical methods, including the study of cognitive changes due to normal aging and neurodegeneration on molecular, cellular, and systems level; (2) Expertise in neurophysiology of non-invasive brain activity measures such as ERP, HEP, and TEPR; (3) Experience in neuro-imaging, including the ability to read and analyze MRI and PET data; (4) Advanced experience in research independence, especially complex statistical analyses, scholarly productivity, and research funding. The proposed research offers a unique opportunity to (1) compare neurophysiological responses to cognitive demand between healthy aging, pre-clinical AD, and MCI/AD; (2) correlate neurophysiological responses to structural brain changes; and (3) examine the intrasubject variability of neurophysiological responses in the short- and long-term. The central hypothesis is that neurophysiological changes will manifest prior to decrements in neuropsychological performance in pre-clinical AD, reflecting a compensatory mechanism for excessive neural recruitment to cope with cognitive task demand. The knowledge gained from my career development and research training will enable me to compete for R01 funding to investigate neurophysiological markers of early neurodegenerative, cognitive, and functional decline in pre-clinical AD. This project will capitalize on KUMC's major research strengths: the NIH-designated Alzheimer's Disease Center, the Hoglund Brain Imaging Center, and the Clinical and Translational Science Unit (NIH CTSA). In summary, this K01-award will bring together my clinical research experience and my new skills in applied neurophysiology of AD. The mentor team and research environment will provide essential support on my track towards research independence.

摘要 这是一个K 01指导研究科学家奖博士Hannes Devos，早期职业生涯， 堪萨斯医科大学物理治疗和康复科学系终身教职 中心虽然我在博士后期间接受了临床研究培训，但我寻求扩大我的科学研究领域， 为成为阿尔茨海默病（AD）应用神经生理学的独立研究人员奠定了基础。 我的主要目标是获得独立，能够领导一个多学科小组进行调查 神经生理学标志物-事件相关电位（ERP）、心跳诱发电位（HEP）和任务- 诱发瞳孔反应（TEPR）-临床前AD的早期神经退行性衰退。我正处于 在我的职业生涯中，在获得帕金森氏症瞳孔测量的初步经验后， 疾病因此，我提出了一个职业发展计划，在这个计划中，我将与临床领域的知名专家一起培训， 方法（Dr. Burns）、神经生理学（Dr. Gustafson）、神经成像（Dr.布鲁克斯和Dr. Burns），以及 研究独立性（Burns博士、布鲁克斯博士和Mahnken博士）。 从这些专家的指导中，我将学到：（1）临床方法的专业知识，包括认知研究 由于正常衰老和神经退行性病变在分子、细胞和系统水平上的变化;（2） 非侵入性脑活动测量的神经生理学，如ERP，HEP和TEPR;（3）经验， 神经成像，包括阅读和分析MRI和PET数据的能力;（4）在以下方面的先进经验： 研究独立性，特别是复杂的统计分析，学术生产力和研究资金。 拟议的研究提供了一个独特的机会，（1）比较神经生理反应的认知 健康老龄化，临床前AD和MCI/AD之间的需求;（2）将神经生理反应与 结构性脑变化;和（3）检查受试者内的神经生理反应的变异性， 短期和长期。核心假设是，神经生理学变化将在 临床前AD的神经心理学表现下降，反映了一种代偿机制， 过度的神经募集以科普认知任务的需求。从我的职业生涯中获得的知识 发展和研究培训将使我能够竞争R 01基金，以研究神经生理学 临床前AD的早期神经退行性、认知和功能下降的标志物。 该项目将利用KUMC的主要研究优势：NIH指定的阿尔茨海默病 中心，Hoglund脑成像中心和临床和转化科学单位（NIH CTSA）。 总之，这个K 01奖将把我的临床研究经验和我在应用领域的新技能结合起来， AD的神经生理学导师团队和研究环境将提供必要的支持我的轨道 走向研究独立。

项目成果

EEG/ERP evidence of possible hyperexcitability in older adults with elevated beta-amyloid.

• DOI: 10.1186/s40035-022-00282-5
• 发表时间: 2022-02-09
• 期刊: Translational neurodegeneration
• 影响因子: 12.6
• 作者: Devos H;Gustafson K;Liao K;Ahmadnezhad P;Estes B;Martin LE;Mahnken JD;Brooks WM;Burns JM
• 通讯作者: Burns JM

Cortical Correlates of Increased Postural Task Difficulty in Young Adults: A Combined Pupillometry and EEG Study.

• DOI: 10.3390/s22155594
• 发表时间: 2022-07-26
• 期刊: SENSORS
• 影响因子: 3.9
• 作者: Kahya, Melike;Liao, Ke;Gustafson, Kathleen M.;Akinwuntan, Abiodun E.;Manor, Brad;Devos, Hannes
• 通讯作者: Devos, Hannes

Reliability and Validity of Pupillary Response During Dual-Task Balance in Parkinson Disease.

• DOI: 10.1016/j.apmr.2020.08.008
• 发表时间: 2021-03
• 期刊: Archives of physical medicine and rehabilitation
• 影响因子: 4.3
• 作者: Kahya M;Lyons KE;Pahwa R;Akinwuntan AE;He J;Devos H
• 通讯作者: Devos H

Reliability of P3 Event-Related Potential During Working Memory Across the Spectrum of Cognitive Aging.

• DOI: 10.3389/fnagi.2020.566391
• 发表时间: 2020
• 期刊: Frontiers in aging neuroscience
• 影响因子: 4.8
• 作者: Devos H;Burns JM;Liao K;Ahmadnezhad P;Mahnken JD;Brooks WM;Gustafson K
• 通讯作者: Gustafson K

Effectiveness of Brain Gaming in Older Adults With Cognitive Impairments: A Systematic Review and Meta-Analysis.

• DOI: 10.1016/j.jamda.2021.05.022
• 发表时间: 2021-11
• 期刊: Journal of the American Medical Directors Association
• 影响因子: 7.6
• 作者: Kletzel SL;Sood P;Negm A;Heyn PC;Krishnan S;Machtinger J;Hu X;Devos H
• 通讯作者: Devos H