Pain and Nutrition in Dementia and Alzheimers PANDA

痴呆症和阿尔茨海默病的疼痛和营养 PANDA

• 批准号: 10644355
• 负责人: Larissa J Strath
• 金额: $ 13.31万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10644355
• 关键词: Acceleration; Achievement; Address; Affect; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease patient; Alzheimer' s disease related dementia; Ancillary Study; Cell Aging; Chronic; Clinical Research; Cognition; Cognitive; Cognitive aging; Communities; Consumption; DNA Methylation; Data; Dementia; Development; Development Plans; Diagnosis; Diet; Dietary Assessment; Dietary Intervention; Disease; Early identification; Elderly; Environment; Environmental Risk Factor; Epigenetic Process; Etiology; Functional disorder; Future; Gene Expression; Genes; Goals; Grant; Health; High Prevalence; Human; Immune; Immune System Diseases; Immune system; Impaired cognition; Individual; Inflammation; Inflammatory; Institution; Intervention; K-Series Research Career Programs; Knowledge; Link; Literature; Maintenance; Measurement; Mediating; Mentors; Methylation; Modality; Modification; Morbidity - disease rate; Nervous System; Nutrient; Nutrition Assessment; Nutritional; Nutritional status; Outcome; Pain; Pain Free; Pain management; Pathologic; Pathology; Pathway interactions; Pattern; Persons; Phase; Physiological; Population; Prevalence; Prevention; Prevention strategy; Reporting; Research; Research Personnel; Risk; Serum; Statistical Data Interpretation; Symptoms; Techniques; Testing; Training; Translational Research; Vitamin A; Vitamin D; Work; age related; aging population; career development; chronic pain; chronic painful condition; clinical pain; cognitive function; comorbidity; design; dietary; effective therapy; epigenetic regulation; epigenome; epigenomics; forging; genome-wide; improved; indexing; innovation; knee pain; methylation pattern; middle age; mild cognitive impairment; multidisciplinary; novel; nutrition; nutritional genomics; nutritional supplementation; pain outcome; pre-clinical; protein expression; side effect; skills; standardize measure; translational scientist

PROJECT ABSTRACT/SUMMARY Growing evidence suggests the presence of dysregulated pain modulation in older adults, and affect which may heighten age-associated risk for chronic pain. Additionally, chronic pain and Alzheimer’s Disease and related dementias (AD/ADRD) are highly prevalent and comorbid in older adults, and research suggests that they may have overlapping etiologies and pathologies. Chronic pain may a predictor for the development of AD, and almost half of AD patients report having pain. Thus, understanding of the shared mechanisms underlying both is critical in order to develop effective treatment and prevention modalities. Recently, epigenetics has been implicated in both disease states, with many modifications of the epigenome that may go on to result in immune system dysfunction, of which is a hallmark of both chronic pain and AD. While there are many environmental factors that can influence the epigenome, nutrition status has been shown to be one of the most common and modifiable factors therein. Thus, it may be efficacious to understand dietary interactions with the epigenome to target epigenetic regulation of the development and maintenance of chronic pain and AD. Therefore, the overall goal for this mentored career development proposal (K99/R00) is to fill this knowledge gap and determine the influence of overall diet pattern as well as Vitamins A and D specifically on the epigenetic environment as it relates to chronic pain and AD/ADRD. Primary training goals for the current proposal are to: Increase knowledge and understanding of measurement techniques used to assess cognitive aging in humans, with a specific focus on mild cognitive impairment, and AD/ADRD; Further expand knowledge of nutri-epigenetics, and apply it to cognitive aging outcomes; Enhance clinical research skills related to the design, conduct and statistical analysis of multidisciplinary studies and rigorous translational research skills to function as an independent investigator. Study 1 (K99 Phase) will assess dietary differences and their associations with differences in epigenetic aging, pain, and cognition in individuals with and without chronic pain. Study 2 (R00 phase) will allow for the assessment of diet pattern as well as vitamin A and D status on DNA methylation patterns, gene and protein expression, pain and cognitive outcomes in older adults with and without mild cognitive impairment. This proposed career development plan extends from the PIs prior work in dietary and immune system modulation of pain, and will forge a path towards understanding and investigating side-effect free nutrigenomic targets that improve pain and AD/ADRD outcomes in older adults.

项目摘要/总结 越来越多的证据表明老年人存在疼痛调节失调， 可能会增加与年龄相关的慢性疼痛风险。此外，慢性疼痛和阿尔茨海默病， 相关性痴呆（AD/ADRD）在老年人中高度流行和共病，研究表明， 它们可能具有重叠的病因和病理。慢性疼痛可能是发展中国家的一个预测因素， 几乎一半的AD患者报告有疼痛。因此，对共享机制的理解 两者的基础对于制定有效的治疗和预防模式至关重要。最近， 表观遗传学与这两种疾病都有牵连，表观基因组的许多修饰可能会导致 导致免疫系统功能障碍，这是慢性疼痛和AD的标志。虽然有 许多环境因素可以影响表观基因组，营养状况已被证明是其中之一 其中最常见的和可修改的因素。因此，了解饮食相互作用可能是有效的 用表观基因组靶向慢性疼痛的发展和维持的表观遗传调节， AD.因此，本辅导式职业发展建议书（K99/R 00）的总体目标是 知识差距，并确定整体饮食模式以及维生素A和D的影响，特别是 表观遗传环境与慢性疼痛和AD/ADRD相关。当前的主要培训目标 建议是：增加知识和了解用于评估认知能力的测量技术 人类衰老，特别关注轻度认知障碍和AD/ADRD;进一步扩大 营养表观遗传学的知识，并将其应用于认知老化的结果;提高临床研究技能 与多学科研究的设计、进行和统计分析以及严格的翻译有关。 研究技能，作为一个独立的调查员。研究1（K99阶段）将评估饮食差异 以及它们与表观遗传衰老、疼痛和认知差异的关系， 慢性疼痛研究2（R 00阶段）将允许评估饮食模式以及维生素A和D 老年人DNA甲基化模式、基因和蛋白质表达、疼痛和认知结果的现状 有无轻度认知障碍这一拟议的职业发展计划延伸到PI之前， 工作在饮食和免疫系统调节疼痛，并将锻造一条通往理解和 研究无副作用的营养基因组靶点，改善老年人的疼痛和AD/ADRD结局。