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，英国和世界上患有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。正是认识到这种严峻的形势，总理在2012年发起了痴呆症挑战。科学背景是，政府和制药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级联假说。但这种方法迄今为止并没有取得明显的成功，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，并期待在理解阿尔茨海默病以及可能的许多或大多数其他痴呆症方面的范式转变。有许多指标表明，痴呆症通常与神经元水平的营养不良有关，这些营养不良可以通过改变生活方式和饮食来逆转或至少改善。如果能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有所帮助的高危人群，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程度的方法。它将应用新的、复杂的分析方法来分析从患者身上测量到的大脑信号，包括电信号（EEG）和心血管（血流/氧合）信号。其目的是创建一种能够提供疾病进展或消退的定量测量的设备，在治疗和/或饮食或生活方式的改变产生有益结果的情况下。我们提出的设备是一个由市售最先进仪器和新型数据分析算法组成的系统。它的独特之处在于它涉及1。同时和非侵入性地评估心血管和神经元/认知振荡，从而评估其相互作用中的功能障碍。最终，以图像和从0到100.3的单个系数来标准化呈现结果。一种相对舒适和廉价的评估方法（特别是与MRI相关方法相比），可以很容易地在同一天或根据需要或期望的频率重复使用。我们将在Addenbrooke医院（剑桥）的10名临床评估的痴呆患者和10名健康对照的帮助下，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使用一系列复杂的方法进行，其中一些方法是完全新颖的，非常有前途。假设该项目取得成功，预计将进行临床试验，包括纵向研究，但这些超出了本提案的范围。尽管如此，我们可以期望实现该设备的概念验证，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，部分原因是使近红外光谱仪（NIRS）专用设计，而不是依赖于灵活的多功能仪器，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.