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

21世纪发达国家面临的最大挑战之一是日益老龄化的人口和日益增长的预期寿命。在英国，近四分之一的人口将在20年内达到65岁或以上。因此，将有更多的人生活在长期存在的慢性健康问题中。这带来了巨大的挑战，特别是在医疗保健领域，需要转向旨在预防或减缓慢性病进展的预防性治疗，以应对这种不断变化的人口结构。帕金森氏症是一种常见的大脑退行性疾病，随着年龄的增长，这种疾病变得更有可能。肌肉僵硬、震颤和缓慢运动的组合提醒临床医生注意它的存在。一旦被称为黑质的大脑区域中一半的神经细胞已经死亡，这些症状就开始被检测到。一旦确诊，疾病的进展是高度可变的。大约一半的确诊患者将在四年内出现严重问题。有证据表明，帕金森氏症实际上在确诊前20年就开始了；它始于大脑的不同部分，进展缓慢，导致更细微的问题。这段间歇期被称为“临床前帕金森氏症”。在此期间会出现某些问题，如嗅觉丧失或某些睡眠障碍，这些问题更有可能是患有这种疾病的人所经历的。然而，目前还不可能确定这些人中谁患有临床前帕金森病，或者一旦被诊断出来，疾病会以多快的速度发展。为了解决这些问题，帕金森病的解剖表型定量MRI项目(qMAP-PD)于2018年在伦敦大学学院惠康人类神经成像中心启动。这是一项使用非侵入性脑扫描技术的纵向研究，目的是了解为什么帕金森氏症如此多变，开发基于个人大脑结构预测疾病进展速度的方法，并在临床前阶段诊断病情。这项研究完全依赖于面对面的评估，因此受到新冠肺炎大流行的影响而显著延迟。从这一时期恢复是复杂、耗时的，并影响了其他一些因素，导致了更多的延误。尽管面临这些前所未有的挑战，这项研究还是设法招募和评估了250多人，现在已经对其中许多人进行了后续评估。为了实现最初的目标，需要短期的额外支持来分析和公布所获得的数据，从而实现最初的实验目标。通过实现这些，旨在减缓病情的战略可以得到更准确的研究，疾病可以更好地在个人身上表现出来，从而使目前的治疗能够根据他们现在和未来的需求进行量身定做。

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.