Cognitive Effects of Opioids in Older Adults

描述(申请人提供)：持续性疼痛，足以导致日常功能严重受损，影响高达50%的老年人。止痛药是用于控制疼痛的最常见的疗法，阿片类药物在老年人慢性致残性疼痛的药物治疗中发挥着越来越重要的作用。阿片类药物治疗的疗效需要与潜在的副作用进行权衡，包括神经认知障碍的风险。到目前为止，还没有研究阿片类药物对老年人神经认知功能的影响。这项拟议的研究将测量羟考酮对健康老年人(65岁)的客观和主观神经认知影响。由于老年人对阿片类药物的反应模式可能与年轻人不同，我们还将在健康的中年(35-55岁)人群中测量羟考酮的客观和主观神经认知影响。通过这种方式，我们将能够使用横断面方法系统地检查老化效应。我们还将描述一定剂量水平的羟考酮在中老年人样本中的药代动力学特征。这项研究集中在NIA的优先研究领域，即疼痛管理和认知障碍。此外，它还阐述了持续性疼痛治疗中一个重要但研究不足的领域。许多关于阿片类药物治疗持续性疼痛的研究没有包括老年人，也缺乏对老年人神经认知影响的检查。该项目非常适合R21机制，因为该项目将建立给一组健康的老年人管理特定水平的阿片类药物的可行性。这一可行性项目的结果将为随后的实验室阿片剂量反应研究以及阿片类药物在患有持续性疼痛的老年人的临床样本中的神经认知和副作用表征提供重要的初步数据和背景信息。

DESCRIPTION (provided by applicant): Persistent pain, sufficient to cause significant impairment in daily functioning, affects up to 50 percent of older adults. Analgesics are the most common therapy used to manage pain, with opioids playing an increasingly important role in the pharmacological treatment of chronic disabling pain in older adults. The efficacy of opioid therapy needs to be balanced against potential side effects, including the risk of neurocognitive impairment. To date, no studies have examined the effects of opioids on the neurocognitive function of older adults. The proposed study will measure the objective and subjective neurocognitive effects of oxycodone in healthy older (>65 years) adults. Because older adults may evidence a different pattern of response to opioid medication than younger adults, we will also measure objective and subjective neurocognitive effects of oxycodone in a healthy middle age (35-55 years of age) population. In this manner we will be able to systematically examine aging effects using cross sectional methodology. We will also characterize the pharmacokinetics of a dose level of oxycodone in a sample of middle age and older adults. This study focuses on priority research areas for the NIA, those of pain management and cognitive impairment. Moreover, it addresses an important but understudied area in the treatment of persistent pain. Much of the research on opioid use for persistent pain has not included older adults and the examination of neurocognitive effects in elders is lacking. This project is well suited for the R21 mechansim as the project will establish the feasability of administring a specific level of opiod medication to a group of healthy older adults. Results of this feasability project will provide important preliminary data and background information for subsequent opiod dose response studies in the laboratory as well as neuorcognitive and side effect characterization of opioids in a clinical sample of older adults with persistent pain.