Norwich Clinical Trial Unit, Norwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, England.
School of Education and Lifelong Learning, Faculty of Social Sciences, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, England.
BMC Neurol. 2019 Sep 7;19(1):223. doi: 10.1186/s12883-019-1447-7.
Hip fracture represents a substantial acute inflammatory trauma, which may constitute a significant insult to the degenerating brain. Research suggests that an injury of this kind can affect memory and thinking in the future but it is unclear whether, and how, inflammatory trauma injures the brain. The impact of Acute SystematiC inflammation upon cerebRospinal fluId and blood BiomarkErs of brain inflammation and injury in Dementia: a study in acute hip fracture patients (ASCRIBED) explores this relationship, to understand the effect of inflammation on the progression of dementia.
This protocol describes a multi-centre sample collection observational study. The study utilises the unique opportunity provided by hip fracture operations undertaken via spinal anaesthesia to collect cerebrospinal fluid (CSF) and blood, to investigate the impact of acute brain inflammation caused by hip fracture on the exacerbation of dementia. We will recruit 200 hip fracture patients with a diagnosis or evidence of dementia; and 200 hip fracture patients without dementia. We will also recruit 'Suitable informants', individuals in regular contact with the patient, to provide further proxy evidence of a patient's potential cognitive decline. We will compare these 400 samples with existing CSF and blood samples from a cohort of dementia patients who had not experienced a systemic inflammatory response due to injury. This will provide a comparison between patients with and without dementia who are suffering a systemic inflammatory response; with stable patients living with dementia.
We will test the hypothesis that hip fracture patients living with dementia show elevated markers of brain inflammation, as well as neuronal injury and Alzheimer-related plaque pathology, in comparison to (1) stable patients living with dementia and (2) hip fracture patients without dementia, as measured by biomarkers in CSF and blood. The findings will address the hypothesis that systemic inflammatory events can exacerbate underlying dementia and inform the search for new treatments targeting inflammation in dementia.
ISRCTN43803769 . Registered 11 May 2017.
髋部骨折代表了一种严重的急性炎症性创伤，可能对退化的大脑造成严重损伤。研究表明，这种类型的损伤可能会影响未来的记忆和思维，但尚不清楚炎症性创伤是如何损伤大脑的。急性系统性炎症对痴呆患者脑脊液和血液中脑炎症和损伤生物标志物的影响：急性髋部骨折患者的研究（ASCRIBED）探讨了这种关系，以了解炎症对痴呆进展的影响。
本方案描述了一项多中心样本采集观察性研究。该研究利用通过脊髓麻醉进行髋部骨折手术提供的独特机会，收集脑脊液（CSF）和血液，以研究由髋部骨折引起的急性脑炎症对痴呆加重的影响。我们将招募 200 名诊断或有痴呆证据的髋部骨折患者；和 200 名无痴呆的髋部骨折患者。我们还将招募“合适的知情人”，即与患者有定期联系的人，以提供患者潜在认知能力下降的进一步代理证据。我们将把这 400 个样本与因受伤而未经历全身性炎症反应的痴呆患者的现有 CSF 和血液样本进行比较。这将提供一个因全身性炎症反应而患有和不患有痴呆的患者之间的比较；与患有稳定型痴呆的患者进行比较。
我们将测试以下假设：与（1）患有稳定型痴呆的患者和（2）无痴呆的髋部骨折患者相比，患有痴呆的髋部骨折患者的 CSF 和血液中的生物标志物显示出更高的脑炎症标志物，以及神经元损伤和阿尔茨海默病相关斑块病理学。研究结果将解决全身性炎症事件是否会加重潜在痴呆的假设，并为寻找针对痴呆炎症的新治疗方法提供信息。
ISRCTN43803769。注册于 2017 年 5 月 11 日。
