Dementia research update

December 7, 2016 at 11:59 am | Posted in Uncategorized | Leave a comment
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The Fragile Brain coverFollowing a request on Twitter, this post summarises some of the major research developments in dementia science between the time when my book The Fragile Brain was submitted (March 2016) and its publication last month (November 2016).

For a more general study of growing older, there’s an OUP VSI (Very Short Introduction) on ageing just out, though I haven’t had a chance to look at it yet.


The big clinical news is surely the failure of the solanezumab trial, based on the amyloid cascade hypothesis. Some researchers reacted by giving reasons why the failure didn’t kill the hypothesis; others remarked that you can’t kill something that’s already dead. Apart from its implications for research, this is another setback for patients desperate for good news.


Good news may yet arrive from treatment trials, but we got some by another route this year, courtesy of big epidemiological studies such as Langa et al. and Matthews et al.. These support the idea that dementia rates may be slowing, at least in Western countries like the UK. That suggests that the lifestyle changes people have made so far may be having an effect.

These changes are sizeable. In the UK, for instance, smoking has dropped from 46% to 19% of adults since 1974, according to the Office for National Statistics. If so much change is possible, perhaps there’s hope for other risk factors like overeating, pollution, and physical inactivity. It would help if governments would take them more seriously, though there are hints of progress here too, such as the new UK sugar tax. Countries in which smoking rates remain high and diets are becoming more Western are storing up trouble – and expense – for future generations.


In research, one obvious change (certainly since I began work on The Fragile Brain) is that neuroimmunology – and the broader acceptance that blood factors can and do affect the brain far more than previously thought – is now mainstream. For example, the journal Neuropsychopharmacology has just issued a table of contents on the topic (Volume 42, Issue 1, January 2017). Emphasis on diabetes and depression as risk factors has increased accordingly, given the importance of inflammation in these disorders. Research into the gut and microbiome, and their potential impact on ageing brains, is also gathering pace (e.g. Sampson et al.).

Complementing this is the growing understanding that the brain’s non-neuronal cells – such as astrocytes, microglia, oligodendrocytes, pericytes and endothelial cells – really matter for neurons’ and synapses’ wellbeing. These formerly neglected cells, and the vascular system, are vital for keeping the brain healthy into old age (see e.g. Ma et al.).

There has also been progress on the notoriously difficult problem of the amyloid peptides’ structures (see for example Riek et al., Xu et al., Wälti et al., Eisenberg et al., and more).

Work on prions, and on the implication that amyloid too may be infectious, also proceeds: see for example the recent Nature Insight review by (of course) John Collinge et al. The other papers in that collection are also well worth a look. For example, the fascinating piece by Rebecca Canter and colleagues looks at neural circuitry failures in neurodegeneration.

Efforts continue to make the impact of new methods, such as organoids, ‘omics’ and neuroimaging, felt in neurodegeneration research, and to organise the masses of data they produce (see e.g. Rollo et al.). It’s becoming clearer that lipids, and the cell membrane, are more important players than previously realised, which potentially opens up new treatment and dietary avenues for research. For proteins, the importance of variants in genes other than ApoE, such as TREM2, is becoming more apparent, and ApoE studies are also branching out.

This is a brief summary of recent developments; there’s much more than I’ve covered here. It’s a fast-moving field, and 2017 should bring plenty of advances in basic research. And treatments? Well, here’s hoping. Perhaps some of the other antibody trials, or alternative approaches such as insulin, will produce encouraging results.

Whatever happens in 2017, in dementia research and elsewhere, I wish you a successful new year.


Work? What a silly idea

March 26, 2014 at 9:40 pm | Posted in Uncategorized | Leave a comment
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A study making headlines today in the Journal of Occupational Health Psychology suggests that having a mentally demanding job before you retire is associated (in about 4000 Americans) with “higher levels of cognitive functioning before retirement, and a slower rate of cognitive decline after retirement”. Use it or lose it, in short.

And who wants to lose it? A retirement spent blowing the kids’ inheritance on having fun is one thing; a retirement blighted by stroke or dementia is quite another.

A letter to my local paper last week, meanwhile, remarked on the way we insist on people ‘finding jobs’, even as companies increasingly use technology to replace them. Or to shift the work elsewhere: the forms which would once have been filled by a secretary are often now completed by customers, online.

Which got me thinking — as I and many before me have thought — about work and the way we organise it.

Frankly, it’s rather silly. The timing’s inept, the concept old-fashioned, and the execution often cruel. For much of history this hasn’t mattered, as there’s been plenty of work to go around; also many people didn’t live long enough to worry about retirement. But things are changing, as the available labour shrinks. And not only shrinks, but shifts towards two extremes: the much-puffed ‘knowledge economy’, and the rest.

  • ‘high-end’ jobs pay relatively well and demand a lot of skills and brainpower (e.g. university teachers and researchers). They also have high workloads and long hours;
  • more manual jobs, which we can’t yet replace with technology, are typically much lower-paid, despite the fact that it’s hard to see how caring for the sick and elderly is less important than teaching kids why Hamlet, or quantum mechanics, matters. Of course, you don’t need extensive training to be a carer.

(We might infer that high pay is perhaps a reward for time invested in previous study? — except that investment bankers can earn far, far more than university lecturers. Is it then a reward for effort, or physical labour? Tell that to a farmer. For danger? Ask a fireman. For being brilliant and/or irreplaceable? That’s what the most highly-paid often seem to be saying, but there’s very little evidence that they’re right.)

There’s less work to go round, especially for those without the best qualifications. And what work there is doesn’t always pay enough to live on. The private sector is on a win-win here. They can get away with paying low wages because the state will fill the gap. They can hike rents, or drive up house prices, because that’s ‘the free market’. They can make profits by pushing their costs onto others, and still whinge about the tax they have to pay — when much of that tax goes on payments that wouldn’t be needed if they weren’t so utterly focused on making money.

In Britain, we hark back to the days when great companies built houses for their workers, or gave their kids schools. That kind of philanthropy may still go on, but we don’t hear much about it. Instead we hear a lot about companies who seem to live by the ancient Roman principle: “homo homini lupus” (“Man is a wolf to man.”) And they have the cheek to complain about government ‘red tape’! Guys, if you behaved better we wouldn’t need to impose the regulation on you — and on everyone else.

As work becomes scarcer, the rhetoric of its desirability intensifies. You’d think humans lived entirely and only to work. The unemployed are stigmatised, their benefits decried (yet the far more expensive pensions of the elderly are OK, because they earned their rewards). Kids are so indoctrinated with the need to find a job that they spend much of their childhood cramming, agonising over exams, struggling with homework, knowing they have to achieve — at a time when they’re dealing with the massive social pressures of growing up. Small wonder some drop out. People who can’t work feel dreadful guilt. Some who lose their jobs are driven to suicide.

There’s something pitiful about a first-year university English Literature student distraught because she’s “wasted time” reading Wuthering Heights when it wasn’t on her course. Or a seventeen-year-old whose only idea about all the cultural riches available to them is how to get work that will pay them enough to buy lots of stuff. Come to that, there’s something pitiful about a middle-aged adult lying awake at night worrying about how they’ll cope with both a sick parent and the demands of running their own household, while working all the hours their job demands. And there’s certainly much to be pitied in the lonely senior, deprived by retirement of company and stimulation, or the hard-working tax-payer who, as they reach retirement, is diagnosed with some appalling illness, like dementia.

Why do we do it this way? It’s bad for our brains, our health and our happiness. At the time of life when we are most able to enjoy ourselves, some of us are working ridiculous hours while others face empty days. Women lose out if they have kids, especially if they choose not to deposit the sprogs in childcare. Some people aren’t paid enough to live on; others earn far more than any human being could reasonably need. Then we reach retirement age, and suddenly that’s it: we’re pensioned off, our productive days over. Yet creativity doesn’t cut out at sixty-five, nor intelligence shrivel at seventy. A man who turns 65 in the UK can expect to live a further 17.8 years, a woman 20.4 years, according to the Office for National Statistics. That’s a lot of years to write off, especially with an ageing population.

There are many ways in which we could change this mess. Most of them are extremely unlikely to happen, not least because the mess didn’t come about by accident. It suits the people in charge, insofar as anyone’s in charge. Yet it may be worth stating some options anyway, if only because they’re far too radical for serious politics and so aren’t often heard. (I’m not a politician, so I don’t need to be serious.)

  • Make the private sector pay its way. Rent caps (why should taxpayers spend masses on housing benefits so that landlords can get rich?). Tackling tax evasion and business subsidies. Redistribution: in the UK this year, a few lucky bankers collected over £5 million each from Barclays Bank. Why are they worth 50 times what we pay our most senior nursing directors, let alone frontline nurses?
  • Encourage job-sharing, volunteering, hobbies and part-time work. Make it acceptable for people of both sexes to take career breaks in midlife. Pay parents better: bringing up kids is hard work. Defusing the social pressures around work and worklessness with clear financial incentives would do wonders for the nation’s health bill, apart from its other benefits.
  • Rethink education. Currently it’s mostly stuffed into our youngest years, and some of it’s pretty irrelevant to most adults. It should be lifelong, as much a part of our routine as running a bank account. That old canard about brain development ceasing around 18 is nonsense.
  • A living wage and/or minimum income guarantee (discussed here in the US context). Many people who’d like to volunteer can’t afford to; many who can afford to can’t spare the time. Making sure that everyone has a minimum guaranteed income to live on would help with at least the first of these problems, as well as reducing the devastating costs of stress-induced mental illnesses. It would also save on the gigantic benefits bill, not least because it would be a good deal simpler to administer than current systems.
  • High-end jobs like running a university, company or bank may be extremely hard and stressful, but the work itself is not intrinsically unpleasant or dangerous (except insofar as the sedentary lifestyle brings health risks). Jobs which are unpleasant and dangerous should be paid more, or workers given a tax break, to express the nation’s gratitude that we don’t have to do this stuff. And if that study I mentioned is correct, perhaps we should be targeting the financial rewards towards encouraging workers to continue their education.
  • Abolish retirement except on health grounds. If work — in moderation — is so good for us, we shouldn’t be driving people away from it. If there’s less work to go round, we need to be more creative in how we organise it — because there’s plenty to do; it’s just that much of it isn’t currently paid work. Making high-end jobs less demanding and low-end work more interesting, and giving people more life space to do unpaid work, would make retirement look less attractive, as well as providing benefits for workers and society.

Work is bound up with many half-acknowledged ideas: about fairness and reciprocity, status and identity. While there was plenty of it, there wasn’t much need to examine its rationales, and how deep-seated feelings and ways of thinking affect them. But work is changing, and we need to change our ideas about work.


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