Dementia: when do I know I have a problem, and what is happening in my brain?

Dr James Burrell is a Senior Research Officer and clinical neurologist whose research interests lie in linking clinical symptoms and pathology in dementia syndromes.

Dr James Burrell

Dr James Burrell

In my work as a clinical neurologist, I often encounter people who are concerned that they might be developing the dreaded d-word: dementia. They report being more forgetful than previously, forgetting the names of people, places or things, or perhaps just not feeling as ‘sharp’ as they once did. In my experience, these sorts of concerns are common. Importantly, however, only a proportion of people with such symptoms actually go on to develop dementia.

Working out who will develop dementia, and more specifically which type of dementia will be developed, is one of the major challenges cognitive researchers and clinicians face. We are presented with two separate, but related problems: first, how can we tell when minor forgetfulness heralds the onset of something more serious? Secondly, if someone has an obvious dementia, how can we make an early and accurate molecular diagnosis?

We know from many well-designed studies that neurodegenerative disorders begin years before any symptoms develop, and that to be effective a treatment will most likely need to start at the very earliest stages, before any significant and permanent damage develops. On the other hand, not everyone with mild cognitive symptoms actually progresses to develop dementia. Being able to accurately identify patients at risk of developing dementia at a very early stage is one of the major goals of research in neurodegenerative diseases.

In the Frontier clinic based here at NeuRA, we are often faced with the opposite problem: we assess patients with early dementia who present with memory, language, or behavioural disturbances, but it can be difficult to work out the specific underlying brain disease. In many ways, our research aims to bridge this gap between the problems related to ageing that people face in their everyday lives and the physical changes in the brain that are ultimately responsible. We use a combination of methods, including detailed clinical assessment, neuropsychological or cognitive testing, sophisticated brain imaging, neurophysiological techniques, gene testing, and even blood and tissue biomarkers, to try and better link cognitive symptoms and specific brain diseases. With collaborators in the UK we have even developed a new app, for cognitive testing in clinical practice (ACEmobile™ for iPad, available from the Apple App Store). Only after we can make an early and accurate diagnosis of a neurodegenerative brain disorder will the hunt for a meaningful treatment really forge ahead.

The art of skeptical neuro-imaging

DuBois Bowman and Ben Cassidy

Assoc Prof Bowman and Ben Cassidy, relaxing at the end of the workshop.

Over the past few decades, the neuroscience community has seen a huge growth in new types of experiments, and methods for analysing data.

But there is no magic wand for data analysis: having a large, flexible toolbox of methods can accidentally lead to the equivalent of baking a cake using salt instead of sugar: the ingredients look sensible and might give great-looking results, but overall you didn’t get what you thought you were making.  Similarly, we could use the correct ingredients, but pour them in the toaster rather than the oven. What’s wrong with that? It still cooks, doesn’t it?

Although you wouldn’t last long making these mistakes as a chef, it’s often less obvious when analogous mistakes are made in science. In my research, I am developing analysis methods for functional neuro-imaging. It’s always fun to facilitate new experiments which were previously out of reach, but equally as important  – though less glamorous – is to generate proper diagnostic tests to validate the research method. This has often been ignored in the excitement of tackling the big questions in brain science.

Neuro-imaging is a particularly difficult field to work within, since it requires collaboration between statistics, physics, psychology, engineering, neuroscience and many other disciplines. No-one can be an expert in everything, but we can at least know what common mistakes to watch out for.

With that in mind, NeuRA hosted a workshop on Skeptical Neuro-imaging Analysis: a course to keep our researchers at the forefront of statistical methods. The workshop was presented by a range of local experts as well as two international speakers, DuBois Bowman (Emery University, USA) and Roland Henry (UCSF, USA).

Key ideas from all speakers were to appreciate the range of assumptions we make at every step in the scientific process, and what we can reasonably assume to gain from different imaging modalities. For example, we can gain more information from an experiment mapping the white-matter pathways in the brain by including information about the heartbeat – otherwise, the heartbeat distorts the measurement.

Overall, the workshop successfully put researchers into a more skeptical mindset when conducting their own research.

‘A grown up is a child with layers on’

Evolution is the gradual development of something into a more complex or better form. I witness this everyday as a paediatric neurologist: A newborn is vulnerable and fully dependent on its parents and during childhood movements become smooth and an infant learns to stand, walk and then run. Compared to development in other species, human children take a long time to grow up. Continue reading