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

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 involves

1. 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.

1. Who will benefit from this research?
Anybody developing a form of dementia is a potential beneficiary, and so correspondingly are the family, social workers, and medical teams that are looking after her or him. The numbers are very large: there were 800,000 people with dementia in the UK in 2012, of whom 17,000 were under 65. It is estimated that by 2021 there will be a million dementia patients in the UK, with a projected growth to 1.7 million by 2051. Looking beyond the UK, to the world as a whole, the predicted number for 2030 is 66 million. There are also potential benefits for industry: for the medical instruments industry in manufacturing the proposed device; and for the pharmaceutical industry in providing an easy-to-use method to follow up and evaluate on a day-to-day basis the effect of treatment. It can of course be used to evaluate any treatment - including drugs, diet, or life style changes.


2. How will they benefit from this research?
The research offers a route to improved diagnosis together with a means of quantifying the severity of the disease. The research is expected to lead to eventually a device that will be easy and reasonably quick (minutes) to use, that is non-invasive, and which does not cause discomfort. It will therefore become feasible to carry out tests at frequent intervals where necessary, to evaluate not only the progression or remission of the disease, but to make explicit evaluations of the efficacy of treatment and the effects of diet, exercise, and lifestyle changes. Although the basic research proposed here requires some relatively expensive general-purpose equipment, it is anticipated that, once we have established exactly what is needed, and with large-scale production, the final device can realistically find a place in every GP's surgery. Manufacturers stand to gain from industrial production of the new device.