MRC TS Award: Defining and predicting variability in early Parkinson's disease using quantitative MRI

MRC TS 奖：使用定量 MRI 定义和预测早期帕金森病的变异性

• 批准号: MR/X023494/1
• 负责人: Christian Lambert
• 金额: $ 20.12万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX023494%2F1
• 关键词: MRC; TS; Award; Defining; predicting

One of the biggest challenges facing developed countries in the 21st centaury is the increasingly aged population and rising life expectancy. In the UK nearly a quarter of the population will be aged 65 or over within 20 years. As a consequence, more people will be living with chronic, long-standing health problems. This poses significant challenges, particularly in healthcare, and will require a shift towards pre-emptive treatments designed to prevent or slow the progression of chronic diseases in order to cope with this changing demographic.Parkinson's disease is a common degenerative disorder of the brain that becomes more likely with age. A combination of muscle stiffness, tremor and slow movements alert the clinician to its presence. These symptoms begin to be detectable once half of the nerve cells within a brain region called the substantia nigra have already died. Once diagnosed, disease progression is highly variable. About half the people diagnosed will develop significant problems within four years.There is evidence that Parkinson's disease actually begins up to 20 years before it is diagnosed; it starts in a different part of the brain and progresses slowly causing more subtle problems. This intervening period is called "pre-clinical Parkinson's". During this period there are certain problems, such as loss of smell or certain sleep disturbances, which are more likely to be experienced by individuals with the condition. However, it is not currently possible to identify who amongst these individuals have pre-clinical Parkinson's or how quickly the disease will progress once diagnosed.To address these questions, the Quantitative MRI for Anatomical Phenotyping in Parkinson's Disease project (qMAP-PD) was started in 2018 at the Wellcome Centre for Human Neuroimaging, UCL. This is a longitudinal study using non-invasive brain-scanning techniques to understand why Parkinson's disease is so variable, develop ways to predict how quickly the disease will progress based on an individual's brain structure and diagnose the condition during the pre-clinical phase. The study was entirely dependent on in-person, face-to-face assessments, and therefore was significantly delayed by the impact of the COVID-19 pandemic. Recovery from this period has been complex, time-consuming and impacted a number of other factors that introduced additional delays. Despite these unprecedented challenges, the study has managed to recruited and assess over 250 individuals, and has now achieved follow-up assessments for many of these. In order to deliver on the original aims, a short period of additional support is required to analyse and publish this acquired data, allowing the original experimental aims to be met. By achieving these, strategies aimed at slowing the condition can be researched more accurately, and the disease can be better characterized within an individual, allowing current treatments to be tailored to their present and future needs.

发达国家在21世纪面临的最大挑战之一是人口老龄化和预期寿命的提高。在英国，近四分之一的人口将在20年内年满65岁或以上。因此，更多的人将生活在慢性、长期的健康问题中。这就带来了巨大的挑战，特别是在医疗保健方面，需要转向旨在预防或减缓慢性疾病进展的先发制人的治疗，以科普这一不断变化的人口结构。帕金森病是一种常见的大脑退行性疾病，随着年龄的增长，这种疾病的发生率更高。肌肉僵硬、震颤和缓慢运动的组合提醒临床医生它的存在。这些症状开始是可检测到的，一旦一半的神经细胞在大脑区域称为黑质已经死亡。一旦确诊，疾病进展是高度可变的。有证据表明，帕金森病实际上在被诊断出来之前的20年就已经开始了;它开始于大脑的不同部位，进展缓慢，导致更微妙的问题。这段时间被称为“临床前帕金森病”。在此期间，有某些问题，如嗅觉丧失或某些睡眠障碍，这些问题更有可能由患有这种疾病的人经历。然而，目前还无法确定这些人中谁患有临床前帕金森病，或者一旦确诊，疾病的进展速度有多快。为了解决这些问题，帕金森病解剖表型定量MRI项目（qMAP-PD）于2018年在伦敦大学学院威康人类神经影像中心启动。这是一项纵向研究，使用非侵入性脑扫描技术来了解帕金森病为什么如此多变，开发方法来预测疾病的进展速度，并在临床前阶段诊断病情。该研究完全依赖面对面的评估，因此受到COVID-19疫情的影响而大幅延迟。从这一时期恢复工作是复杂和费时的，并影响到其他一些因素，造成更多的拖延。尽管面临这些前所未有的挑战，该研究仍成功招募和评估了250多人，现在已对其中许多人进行了后续评估。为了实现最初的目标，需要短期的额外支持来分析和发布这些获得的数据，从而实现最初的实验目标。通过实现这些目标，可以更准确地研究旨在减缓病情的策略，并且可以在个体内更好地表征疾病，从而使当前的治疗方法能够适应他们现在和未来的需求。

项目成果

Outcome Measures for Disease-Modifying Trials in Parkinson's Disease: Consensus Paper by the EJS ACT-PD Multi-Arm Multi-Stage Trial Initiative.

• DOI: 10.3233/jpd-230051
• 发表时间: 2023
• 期刊: JOURNAL OF PARKINSONS DISEASE
• 影响因子: 5.2
• 作者: Gonzalez-Robles, Cristina;Weil, Rimona S.;van Wamelen, Daniel;Bartlett, Michele;Burnell, Matthew;Clarke, Caroline S.;Hu, Michele T.;Huxford, Brook;Jha, Ashwani;Lambert, Christian;Lawton, Michael;Mills, Georgia;Noyce, Alastair;Piccini, Paola;Pushparatnam, Kuhan;Rochester, Lynn;Siu, Carroll;Williams-Gray, Caroline H.;Zeissler, Marie-Louise;Zetterberg, Henrik;Carroll, Camille B.;Foltynie, Thomas;Schrag, Anette
• 通讯作者: Schrag, Anette

Refining the Diagnostic Accuracy of Parkinsonian Disorders using Metaphenomic Annotation of the Clinicopathological Literature

使用临床病理文献的元表型注释提高帕金森病的诊断准确性

• DOI: 10.1101/2023.12.12.23299891
• 发表时间: 2023
• 作者: Massey Q