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Where next for dementia research?

Writing about the science of dementia has been different from any of my previous book projects in one rather sad respect. This time I have never had to explain the topic, or my choice of it. Dementia, once hidden in homes and institutions, has come out of the shadows. Almost everyone I know is afraid of it, and many have felt its impact on sufferers and their families.

Modern medicine has done well in helping Western citizens live longer. So have other changes like improved diets, better public hygiene, and less smoking. Dementia, which is primarily though not entirely age-related, has come to prominence in part as other lethal diseases have diminished. It recently surpassed heart disease as the number one killer in England and Wales (overall and in women, according to the UK Office for National Statistics). Dementia is also now being highlighted by charities convinced that, as with cancer before it, fear and stigma make patients’ and carers’ lives worse.

Charity campaigners also want dementia care and research to get much more funding. Diseases which affect brains tend to come off worse in the competition for resources, especially for charitable giving. As well as funds, researchers need volunteers for studies, including younger adults (if you are in the United Kingdom you can volunteer at Join Dementia Research). Dementia research needs all the help it can get, because this is an immensely challenging and complex problem to solve.

Just why is dementia so difficult? One reason is of course the sheer complexity of human brains. Dementia research must consider not only the interactions of billions of neurons and trillions of synapses, with all their proteins, lipids, ions, and genetic material, but also the roles of non-neuronal brain cells such as microglia, astrocytes, and oligodendrocytes. There is still much to do, for instance, to sort out the contributions of cholesterol signalling, or understand whether, and when, microglia in neurodegenerative disorders are helping the brain and/or harming it.

Until recently we have not had the tools to assess the leading hypotheses about what underlies dementia in human beings.

Another reason, as so often in science, is to do with methods. Until recently we have not had the tools to assess the leading hypotheses about what underlies dementia in human beings. In addition, several of the brain regions which may be crucial early sites of damage in dementia are buried deep in the brain, making them hard to study. There has also been a chronic shortage of donor brains for pathological analysis.

Now, however, technical advances are having a gigantic impact on the field. New imaging techniques can ‘see’ key brain proteins, or changes in microglia, astrocytes, and the white matter which connects brain regions, in living people. Speedier mass analysis of genes and proteins has facilitated the search for mechanisms. Neuroimaging can look at functional connectivity – networking between different parts of the brain. And new ways of obtaining cell samples, such as making microglia from stem cells, look set to overcome many of the problems with older in vitro studies.

A third reason why dementia is so hard a challenge is that its science must extend beyond the brain: this condition is a whole-body disorder. Here again, considerable advances have been made lately in understanding how problems with other organs, such as the heart and pancreas, can push an ageing brain towards degeneration. Alongside this, we now have a much better understanding of the risk factors which may raise our chances of getting dementia in old age.

Perhaps the most important conclusion to have emerged from research so far is that the processes underlying dementia seem to start long before the disorder becomes apparent. Very long before: decades, not years. That is a huge problem for any cure – should one emerge from the clinical trials currently in progress – because new drugs are usually extremely expensive. Given how many people are at risk of dementia, the costs of having to treat them all for, say, 20 years before symptoms appear – and it might be longer – are unaffordable. And if the drugs have unpleasant side effects, the prospect for patients isn’t great either.

Yet thinking of dementia as a whole-body condition brings the hope that looking after our physical health can help stave off later problems. For now, we cannot cure dementia. We can however try to delay it until, to be blunt, we die of something else. Research suggests that dementia rates may already be leveling off in Britain and Europe because fewer people are smoking and getting heart disease. Eating healthily, taking plenty of exercise, staying sociable … all the familiar things we’re told to do to keep our hearts in good condition apply to our brains as well, and more so as we age.

Lifestyle changes aren’t easy. While we await a cure, though, they’re our best hope of avoiding the shadows of dementia.

Featured image credit: Neurons by geralt. CC0 public domain via Pixabay.

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