Chronic Pain and Risk of Alzheimer's-Related Neurodegeneration

慢性疼痛和阿尔茨海默病相关神经变性的风险

• 批准号: 10644253
• 负责人: Tyler Reed Bell
• 金额: $ 13.14万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-15 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10644253
• 关键词: Address; Adult; Affect; Age; Aging; Alzheimer associated neurodegeneration; Alzheimer' s Disease; Alzheimer' s disease brain; Alzheimer' s disease risk; Amyloid; Amyloid beta-Protein; Amyloidosis; Animal Model; Animals; Automobile Driving; Biological; Biological Markers; Biological Process; Biology; Brain; Brain region; California; Chronic; Cognitive aging; Competence; Complement; Data; Data Set; Dementia; Diagnosis; Early Diagnosis; Education; Elderly; Environment; Female; Framingham Heart Study; Goals; Health; Health Care Costs; Helping to End Addiction Long-term; Human; Impaired cognition; K-Series Research Career Programs; Knowledge; Light; Link; Measures; Memory; Mentors; National Institute on Alcohol Abuse and Alcoholism; Nerve Degeneration; Neuroanatomy; Neuronal Injury; Pain; Pain management; Pathologic; Persons; Predisposition; Proteins; Psychiatry; Race; Research; Research Personnel; Retrospective Studies; Risk; Risk Factors; Risk Reduction; Sampling; Statistical Data Interpretation; Thick; Training; Training Activity; Twin Studies; United States; United States National Institutes of Health; Universities; Vietnam; Work; brain volume; career development; chronic pain; dementia risk; depressive symptoms; ethnic minority; factor A; follow-up; high risk; improved; innovation; interest; locus ceruleus structure; middle age; mild cognitive impairment; modifiable risk; multidisciplinary; multiple chronic conditions; multiple datasets; neurofilament; neuroimaging; neuron loss; novel; opioid use; physical inactivity; preventive intervention; programs; racial minority; religious order study; secondary analysis; sex; skills; tau Proteins

7. PROJECT SUMMARY The long-term goal of the proposed career development award is to provide the training necessary to develop an independent research program investigating how chronic pain is related to dementia risk. Such research is timely given recent links between chronic pain and a doubled risk of dementia due to Alzheimer's disease (AD). Chronic pain may lead to general, AD-unspecific, neurodegeneration that increases susceptibility to AD dementia, supported by studies linking chronic pain to smaller brain volumes in adults. Alternatively, recent animal studies suggest that the biological processes underneath chronic pain may promote amyloidosis and tau seeding, but there is less focus on the relationship of chronic pain and AD-related neurodegeneration in humans. A training emphasis focused on incorporating biological measures will complement my existing expertise in chronic pain, cognitive aging, and advanced statistical analysis to conduct this research program. The proposed training goals are to: 1) attain proficiency in neuroanatomy and neuroimaging relevant to aging and AD; 2) obtain competence in assessment and biology of pain; and 3) establish a multidisciplinary program studying brain changes and AD risk. Training will involve a combination of formal coursework, and hands-on activities, and discussion with mentors and other field experts. The Department of Psychiatry at the University of California San Diego is an ideal environment for the proposed training activities with access to world-renown researchers and research centers focused on chronic pain, neuroimaging, and Alzheimer's disease as well as an excellent departmental record of career development for junior researchers. The proposed project will examine how chronic pain relates to indicators of general neurodegeneration and AD-related neurodegeneration across independent samples of older adults including the Framingham Heart Study, the Religious Orders Study/Memory Aging Project, and the Vietnam Era Twin Study of Aging. Aim 1 will examine how chronic pain relates to indicators of general neurodegeneration, including brain age, an estimation of age based on thickness/volume across a wide arrange of AD-unspecific brain regions, as well as neurofilament light, a protein released during neurodegeneration. Aim 2 will examine how chronic is associated with indicators of AD-related neurodegeneration. Indicators include AD brain signatures capturing thickness/volume and mean diffusivity in AD-vulnerable brain regions, biomarkers of amyloid and tau, and diagnosis of mild cognitive impairment and AD dementia. Analyses will help clarify how chronic pain contributes to dementia risk, either through general neurodegeneration or AD-related neurodegeneration. Multiple datasets will improve the rigor of analyses by allowing for replication.

7。项目摘要 拟议的职业发展奖的长期目标是提供开发必要的培训 一项独立研究计划，研究了慢性疼痛与痴呆症风险有何关系。这样的研究是 及时鉴于由于阿尔茨海默氏病而导致的慢性疼痛与痴呆症的两倍风险之间的联系 （广告）。慢性疼痛可能会导致一般，无标准的神经变性，从而增加对AD的敏感性 痴呆症，由将慢性疼痛与成年人的脑量较小的研究联系起来的支持。另外，最近 动物研究表明，慢性疼痛下的生物学过程可能会促进淀粉样变性和 tau播种，但对慢性疼痛和与广告相关的神经退行性的关系的关注较少 人类。培训重点是纳入生物学措施，将补充我现有的 慢性疼痛，认知衰老和高级统计分析的专业知识，以进行该研究计划。 拟议的培训目标是：1）获得与衰老有关的神经解剖学和神经影像学 和广告； 2）获得疼痛评估和生物学的能力； 3）建立一个多学科计划 研究大脑变化和AD风险。培训将涉及正式课程和动手的结合 活动以及与导师和其他现场专家的讨论。大学精神病学系 加利福尼亚圣地亚哥是拟议的培训活动的理想环境，获得世界著名的培训活动 研究人员和研究中心着重于慢性疼痛，神经影像学和阿尔茨海默氏病以及 初级研究人员的职业发展的出色部门记录。拟议的项目将 检查慢性疼痛如何与一般神经变性和广告相关的指标相关 跨老年人的独立样本的神经变性，包括弗雷明汉心脏研究， 宗教秩序研究/记忆衰老项目以及越南时代的衰老研究。 AIM 1将检查 慢性疼痛与一般神经退行性的指标（包括脑年龄）如何相关 基于厚度/体积的广泛布置，大脑区域以及神经丝 光，一种在神经退行性期间释放的蛋白质。 AIM 2将检查慢性与 与广告相关的神经变性指标。指标包括捕获厚度/音量的广告脑签名 以及在可膨胀的大脑区域，淀粉样蛋白和tau的生物标志物以及轻度诊断中的平均扩散率 认知障碍和痴呆症。分析将有助于阐明慢性疼痛如何导致痴呆症风险， 通过一般的神经变性或与AD相关的神经变性。多个数据集将改善 通过允许复制来严格分析。