Pain and Nutrition in Dementia and Alzheimers PANDA

项目摘要/摘要 越来越多的证据表明，在老年人中存在调节失调的疼痛调制，并影响 可能会增加与年龄相关的慢性疼痛的风险。此外，慢性疼痛和阿尔茨海默氏症以及 相关痴呆症(AD/ADRD)在老年人中非常普遍，并伴有痴呆，研究表明 它们可能有重叠的病因和病理。慢性疼痛可能是糖尿病发生的预测因子 AD，几乎一半的AD患者报告有疼痛。因此，对共享机制的理解 将两者结合起来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状态都有关联，表观基因组的许多修改可能会 导致免疫系统功能障碍，这是慢性疼痛和阿尔茨海默病的标志。虽然有 影响表观基因组的环境因素很多，营养状况被证明是其中之一 其中最常见和可修改的因素。因此，了解饮食之间的相互作用可能是有效的。 利用表观基因组靶向慢性疼痛的发生和维持的表观遗传调节 广告。因此，这份有指导的职业发展提案(K99/R00)的总体目标是填补这一空白 知识差距和确定总体饮食模式以及维生素A和D对 表观遗传环境，因为它与慢性疼痛和AD/ADRD有关。当前的主要培训目标 建议是：增加对用于评估认知能力的测量技术的知识和理解 人类的老龄化，特别关注轻度认知障碍，以及AD/ADRD；进一步扩大 营养表观遗传学知识，并将其应用于认知老化结果；提高临床研究技能 与多学科研究和严格翻译的设计、实施和统计分析有关 具备独立调查人员的研究技能。研究1(K99阶段)将评估饮食差异 及其与有无表观遗传衰老、疼痛和认知差异的关系 慢性疼痛。研究2(R00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、基因和蛋白表达、疼痛和认知结果的研究现状 伴有和不伴有轻度认知障碍。这项拟议的职业发展计划是从先前的绩效指标延伸而来的 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 研究改善老年人疼痛和AD/ADRD结局的无副作用营养组学靶点。

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.