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，并影响 此外，可能会增加与年龄相关的慢性疼痛和阿尔茨海默病的风险。 相关痴呆症 (AD/ADRD) 在老年人中非常普遍且存在共病，研究表明 它们可能具有重叠的病因和病理学，慢性疼痛可能是发展的预测因素。 AD，几乎一半的 AD 患者报告有疼痛，因此，了解共同的机制。 为了开发有效的治疗和预防方式，两者的基础至关重要。 表观遗传学与这两种疾病状态有关，表观基因组的许多修饰可能会影响 导致免疫系统功能障碍，这是慢性疼痛和 AD 的标志。 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 因此，了解饮食相互作用可能是有效的。 与表观基因组一起针对慢性疼痛的发展和维持的表观遗传调控 因此，本指导性职业发展提案（K99/R00）的总体目标就是填补这一空白。 知识差距并确定整体饮食模式以及维生素 A 和 D 的具体影响 表观遗传环境与慢性疼痛和 AD/ADRD 相关。 建议是： 增加对用于评估的测量技术的了解和理解 人类衰老，特别关注轻度认知障碍和AD/ADRD； 营养表观遗传学知识，并将其应用于认知衰老结果；提高临床研究技能； 涉及多学科研究的设计、实施和统计分析以及严格的转化 作为独立研究者的研究技能 研究 1（K99 阶段）将评估饮食差异。 以及它们与患有和不患有这种疾病的个体的表观遗传衰老、疼痛和认知差异的关系 研究 2（R00 阶段）将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 无论有或没有轻度认知障碍，本提议的职业发展计划均源自之前的 PI。 致力于饮食和免疫系统对疼痛的调节，并将开辟一条理解和治疗疼痛的道路 研究改善老年人疼痛和 AD/ADRD 结局的无副作用营养基因组目标。