A device to detect and measure the progression of dementia by quantifying the interactions between neuronal and cardiovascular oscillations

这项研究的社会背景是人口迅速老龄化，英国和世界上患痴呆症的人数正在增加。据预测，到2030年，全球将有6600万人患有痴呆症。正是认识到这一严峻形势，首相于2012年发起了痴呆症挑战。科学背景是，政府和制药行业已经并正在将大量资源用于阿尔茨海默病。几乎所有这些都是基于淀粉样蛋白级联假说。但到目前为止，这种方法并没有取得显著的成功，而且看起来越来越令人怀疑。现在有强有力的论据支持寻找替代方案，并预期对阿尔茨海默病的理解将发生范式转变，可能还有许多或大多数其他痴呆症。有许多迹象表明，痴呆症通常与神经元层面的营养缺失有关，而这些可能会通过改变生活方式和饮食而得到逆转，或至少得到改善。如果能够设计出一种简单的方法来监测痴呆症的严重程度，并确定早期补救措施可能对其有帮助的高危人群，这将是非常有利的。因此，我们建议开发一种基于物理学的量化痴呆症程度的方法。它将应用新的、复杂的分析方法来测量患者的大脑信号，包括脑电图（EEG）信号和心血管（血流/氧合）信号。其目的是创造一种设备，在治疗和/或改变饮食或生活方式产生有益结果的情况下，能够提供疾病进展或消退的定量测量。我们提出的设备是一个由商业上可用的最先进的仪器和新颖的数据分析算法组成的系统。它的独特之处在于它涉及1。同时无创地评估心血管和神经元/认知振荡，从而评估它们相互作用中的功能障碍。最终，以图像和单个系数（从0到100.3）的形式对结果进行标准化表示。一种相对舒适和便宜的评估方法（特别是与核磁共振相关的方法相比），可以在同一天或根据需要或期望的频率轻松重复。我们将在阿登布鲁克医院（剑桥）的10名临床评估的痴呆患者和10名健康对照者的帮助下，测试该设备的可行性，并开发必要的数据分析算法。数据分析将全部在兰开斯特进行，使用一系列复杂的方法，其中一些是完全新颖的，非常有前途的。假设企业是成功的，它可能会导致反过来临床试验，包括纵向研究，但这些都超出了目前的建议的范围。尽管如此，我们仍有望实现该设备的概念验证，并在临床环境中运行。从长远来看，我们预计该设备的成本可以大幅降低，部分原因是近红外光谱仪（NIRS）是专门设计的，而不是依赖于灵活的多用途仪器，部分原因是大规模生产。

The social context of the research is the rapidly ageing population, and the fact that the number of people in the UK and the world experiencing dementia is increasing. It is predicted that 66 million individuals worldwide will have dementia in 2030. It was in recognition of this grim situation that the Prime Minister launched the Dementia Challenge in 2012.The scientific context is that vast resources have been and are being expended on Alzheimer's disease by governments and the pharmaceutical industry. Almost all of these are based on the amyloid-cascade hypothesis. But this approach has not been notably successful to date, and is looking increasingly doubtful. There are now powerful arguments in favour of looking at alternatives and anticipating a paradigm shift in the understanding of Altzheimer's disease and, probably, of many or most other dementias. There are many indicators suggesting that dementia is often connected with nutritional failures at the neuronal level and that these may be reversed, or at least ameliorated, by changes in lifestyle and diet. It will be enormously advantageous if a simple means can be devised to monitor the severity of dementia, and to identify the at-risk population for whom early remedial action is likely to be helpful. We therefore propose to develop a method of quantifying the degree of dementia, based on physics. It will apply new, sophisticated, analysis methods to brain signals measured from patients, including both electrical (EEG) signals and cardiovascular (blood flow/oxygenation) signals. The intention is to create a device that will be able to provide quantitative measurements of disease progression - or regression in cases where treatment and/or changes in diet or lifestyle are yielding beneficial results. The device we propose is a system consisting of commercially-available state-of-the-art instruments plus novel data analysis algorithms. Its unique features are that it involves1. Evaluation of both the cardiovascular and neuronal/cognitive oscillations simultaneously and noninvasively, leading to an assessment of the dysfunction in their mutual interactions.2. Eventually, a standardised presentation of the results in terms of images and a single coefficient spanning from 0 to 100.3. A relatively comfortable and inexpensive assessment method (especially when compared to MRI-related methods) that can easily be repeated either in the same day or as frequently as is needed or desired.We will test the feasibility of the device, and develop the necessary data analysis algorithms, with the help of 10 clinically assessed dementia patients and 10 healthy controls, in Addenbrooke's Hospital (Cambridge). The data analysis will all be carried out in Lancaster using a range sophisticated methods, some of which are completely novel and highly promising. Assuming that the enterprise is successful, it may be expected to lead in turn to clinical trials, including longitudinal studies, but these are beyond the scope of the present proposal. Nonetheless we can expect to achieve proof-of-concept for the device, operating in a clinical environment.In the longer term, we anticipate that the cost of the device can be substantially reduced, partly by making the near-infra-red-spectrometer (NIRS) purpose-designed, rather than relying on a flexible multi-purpose instrument, and partly by mass-production.