Chronic Pain and Risk of Alzheimer's-Related Neurodegeneration

7.项目总结 拟议的职业发展奖的长期目标是提供发展所需的培训。 一项独立的研究计划，调查慢性疼痛与痴呆症风险的关系。这样的研究是 考虑到最近慢性疼痛与阿尔茨海默病导致的痴呆症风险加倍之间的联系，这一点是及时的 (Ad)。慢性疼痛可能导致全身性的、非AD特异性的神经变性，从而增加对AD的易感性 痴呆症，由研究支持将慢性疼痛与成年人较小的脑体积联系起来。或者，最近 动物研究表明，慢性疼痛背后的生物过程可能会促进淀粉样变性和 Tau种植，但较少关注慢性疼痛与AD相关神经变性的关系。 人类。侧重于纳入生物措施的培训将补充我现有的 在慢性疼痛、认知老化和高级统计分析方面的专业知识，以进行这项研究计划。 拟议的培训目标是：1)熟练掌握与衰老相关的神经解剖学和神经成像 和AD；2)获得疼痛评估和生物学方面的能力；3)建立一个多学科的计划 研究大脑变化和阿尔茨海默病风险。培训将包括正式课程和实践相结合。 活动，以及与导师和其他实地专家的讨论。大学精神病学系 加州圣地亚哥的圣迭戈是一个理想的环境，为拟议的培训活动，与世界知名 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 初级研究人员在院系职业发展方面的优秀记录。拟议的项目将 检查慢性疼痛与一般神经变性指标和AD相关指标之间的关系 包括弗雷明翰心脏研究在内的老年人独立样本的神经退行性变 宗教教团研究/记忆老龄化项目，以及越南时代的双胞胎老龄化研究。Aim 1将检查 慢性疼痛如何与一般神经退行性变的指标有关，包括脑年龄，年龄的估计 根据广泛排列的AD非特异性脑区以及神经丝的厚度/体积 光，一种在神经退化过程中释放的蛋白质。目标2将研究慢性疾病与 阿尔茨海默病相关神经变性的指标。指标包括AD脑信号捕获厚度/体积 以及阿尔茨海默病易患脑区的平均弥散率、淀粉样蛋白和tau的生物标记物，以及轻度 认知障碍和阿尔茨海默病。分析将有助于澄清慢性疼痛如何导致痴呆症风险， 通过全身神经退行性变或AD相关神经退行性变。多个数据集将提高 通过允许复制来提高分析的严密性。

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.