Chronic Pain and Risk of Alzheimer's-Related Neurodegeneration

7.项目摘要 拟议的职业发展奖的长期目标是提供必要的培训， 一个独立的研究项目，调查慢性疼痛与痴呆症风险的关系。这类研究 鉴于最近慢性疼痛与阿尔茨海默病导致的痴呆症风险增加一倍之间的联系， （AD）。慢性疼痛可能导致全身性、AD非特异性、神经退行性变，增加对AD的易感性 老年痴呆症，这一点得到了将慢性疼痛与成年人较小的脑容量联系起来的研究的支持。或者，最近 动物研究表明，慢性疼痛下的生物学过程可能促进淀粉样变性， Tau播种，但对慢性疼痛和AD相关神经退行性变的关系关注较少， 人类以纳入生物措施为重点的培训将补充我现有的 在慢性疼痛，认知老化和先进的统计分析专业知识进行这项研究计划。 建议的培训目标是：1）熟练掌握与衰老相关的神经解剖学和神经影像学 和AD; 2）获得疼痛评估和生物学能力; 3）建立多学科计划 研究大脑变化和AD风险。培训将包括正式的课程作业和动手操作 活动，并与导师和其他领域专家进行讨论。大学精神病学系 加州圣地亚哥是一个理想的环境，拟议的培训活动，获得世界知名的 研究人员和研究中心专注于慢性疼痛，神经成像和阿尔茨海默病以及 初级研究人员职业发展的优秀部门记录。拟议项目将 研究慢性疼痛与一般神经退行性变和AD相关指标的关系 在老年人的独立样本中进行神经退行性变研究，包括心脏病研究， 宗教秩序研究/记忆老化项目，以及越南时代的老化双胞胎研究。目标1将检查 慢性疼痛如何与一般神经退行性变的指标相关，包括大脑年龄，年龄估计 基于广泛排列的AD非特异性脑区域以及神经丝的厚度/体积， 光是神经退化时释放的一种蛋白质目标2将研究慢性与 AD相关神经退行性变的指标。指标包括AD脑信号，捕获厚度/体积 AD易感脑区的平均扩散率、淀粉样蛋白和tau蛋白的生物标志物以及轻度AD的诊断。 认知障碍和AD痴呆。分析将有助于阐明慢性疼痛如何导致痴呆症风险， 无论是通过一般的神经退行性变还是AD相关的神经退行性变。多个数据集将改善 通过允许复制来提高分析的严谨性。

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.