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.

21世纪发达国家面临的最大挑战之一是人口越来越大，预期寿命不断提高。在英国，将近四分之一的人口将在20年内年龄在65岁以上。结果，越来越多的人将患有慢性，长期存在的健康问题。这提出了重大挑战，特别是在医疗保健中，需要转向旨在预防或减慢慢性疾病进展以应对这种不断变化的人口统计学的预先治疗。Parkinson的疾病是大脑的常见变性疾病，随着年龄的增长而变得更有可能。肌肉僵硬，震颤和缓慢运动的结合使临床医生的存在提醒。一旦一个称为黑质的大脑区域内的一半神经细胞已经死亡，这些症状就开始被发现。一旦诊断出，疾病的进展就高度可变。大约一半的被诊断的人会在四年内出现重大问题。它从大脑的另一部分开始，并缓慢地导致更细微的问题。这段介入时期称为“临床前帕金森氏症”。在此期间，存在某些问题，例如气味或某些睡眠障碍，患有这种情况的人更有可能经历。但是，目前无法确定这些人中谁患有临床前帕金森氏症或疾病一旦诊断出疾病的进展速度。这是一项纵向研究，使用非侵入性的脑扫描技术来理解帕金森氏病为什么如此可变的方式，开发出预测疾病基于个人的大脑结构的快速进展的方法，并在临床前阶段诊断疾病​​。这项研究完全取决于面对面的面对面评估，因此由于19号大流行的影响而显着延迟了。从这一时期恢复是复杂的，耗时的，并影响了引入其他延迟的许多其他因素。尽管存在这些前所未有的挑战，但该研究还是设法招募和评估了250多名个人，现在已经对其中许多人进行了后续评估。为了实现最初的目的，需要短暂的额外支持以分析和发布此获得的数据，从而实现了原始的实验目标。通过实现这些目标，可以更准确地研究旨在减慢病情的策略，并且可以在个人内部更好地表征该疾病，从而可以根据目前和未来的需求量身定制当前治疗方法。

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