COLUMBO’S DEMISE FLAGS MECHANISM FOR ACCELERATED DEMENTIA

Columbo, played by Peter Falk, suffered with severe dementia for several years before he died in 2011 aged 83

A recent article in the Daily Mail described how Peter Falk, the actor who played Lieutenant Columbo in the famous 70’s detective series by the same name, rapidly declined from mild into severe dementia in just one year. In early 2007 he was acting in a feature film, but by the end of that same year, after a series of dental operations, his daughter was in court filing for legal guardianship of her father because he could no longer recognise familiar people, places or objects. Such tragic stories inspired recently published research investigating possible links between acceleration of progression from mild to severe dementia and seemingly unrelated health problems.

Professor Clive Holmes and colleagues at the University of Southampton published a paper in last month’s Neurology journal, which may provide an explanation for the mighty Columbo’s rapid descent into severe dementia. They monitored a group of 300 people with dementia over 6 months and found that, when certain elements of the immune system were mobilised, the incidence of certain neuropsychiatric symptoms doubled. This may suggest that Peter Falk’s rapid decline into severe dementia may have been caused not by the series of dental operations per se, but rather his immune system’s response to those operations. Professor Holmes’s investigation observed elevated concentrations of tumour necrosis factor (TNF), amongst others, in individuals whose dementia-related “sickness behaviour” worsened during the 6 month monitoring period.

TUMOUR NECROSIS FACTOR – double-edged sword

TNF is involved in the inflammatory response to tissue damage and its major role is to regulate the function of immune cells. TNF is also something of a grim reaper as far as cells in our bodies are concerned, as it can induce apopotosis – programmed cell death. Apoptosis might sound like a bad idea but it is actually very important for cells to have a self-destruct button, otherwise removal of malfunctioning cells would be impossible. TNF is a natural component of our immune system that kills off, amongst other things, dangerous damaged cells that start to multiply out of control i.e cancerous tumour cells: Tumour – cancer; Necrosis – killing; Factor – agent. So, when you see TNF, think “Cancer Killing Agent.” However in a person with Alzheimer’s disease, whose brain cells are being increasingly clogged up with neurofibrillary tangles and stuck together with the accumulating amyloid plaques, it seems that high levels of TNF make matters worse by accelerating the onset of severe dementia.

HALTING DEMENTIA with ARTHRITIS DRUGS?

TNF has long been implicated in autoimmune illnesses such as rheumatoid arthritis. Many drug companies have invested vast sums of money in order to bringing anti-TNF drugs to market as an effective treatment for rheumatoid arthritis. Many severely arthritic individuals across the globe are currently enjoying significantly improved quality of life as a result of using such “biologics” to reduce the swollen joints that often leave people with terrible pain and significantly reduced mobility. But that’s not all. Recent studies have revealed that TNF plays a significant role in the development of Alzheimer’s disease and that treatment with anti-TNF drugs can improve dementia symptoms considerably. Indeed, more than 10 years ago a Danish study revealed that levels of TNF in elderly people were elevated and that TNF levels were positively correlated with dementia. An American study came to a similar conclusion. But of course back then these marvellous anti-TNF drugs hadn’t yet hit the market.

Unfortunately the anti-TNF drugs currently taken by individuals with arthritis are largely ineffective in combating dementia. This is because they simply cannot get from the blood stream into the brain (unless they are injected directly into the spine.) This is because the Blood Brain Barrier (BBB), which wraps around every blood vessel that passes through the brain, tightly regulates which molecules are allowed into the brain. Large molecules like these dementia-smashing anti-TNFs are most definitely “not on the list” so although there are many elderly arthritis sufferers with plenty of the good stuff sloshing around in their blood stream, it simply can’t get into the party. In their current form these drugs are unlikely to play a significant role in keeping dementia at bay given how impractical, not to mention dangerous (given the infection risk), repeated spinal injections are.

TROJAN HORSE TO THE RESCUE?

Anti-TNF compounds riding Trojan horses may one day help to delay the onset of Alzheimer’s disease for us all

Brand new drug technologies can however attach therapeutic compounds to naturally-occuring molecules that are on the BBB list  – a so-called “molecular Trojan horse.”  Special transporter proteins embedded in the BBB “recognise” the shape of the naturally-occuring molecule as friend rather than foe, allowing it to attach to the transporter protein and be pulled, along with the attached anti-TNF compound, inside the brain. Once drug companies have managed to create anti-TNF Trojan molecules, acceleration of dementia can be prevented by suppressing TNF activity in the brain. In the not too distant future, we might all soon find ourselves keeping Alzheimer’s at bay with anti-TNF drugs that ride Trojan horses to the rescue by defending our brains from the perils of TNF “friendly fire.”

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Dr Jack is on The One Show on Mon 1st Aug 2011 at 7pm

What do green spaces (parks, fields, commons etc.) do to the human brain? Why do people drop litter? How does visible evidence of anti-social behaviour affect the way other people behave? How would people behave if those responsible for keeping one of London’s finest Royal Parks clean were to down tools for an entire weekend?

All of these questions were asked of Dr Jack by The One Show reporter Justin Rowlatt in Hyde Park where the Keep Britain Tidy campaign ran an interesting experiment over the weekend to see how people would react if the rubbish they dropped was left to accumulate. This brainpost details some of the background to Dr Jack’s comments on The One Show (Mon 1st Aug, BBC1, 7pm).

Spending time in green spaces reduces blood pressure, increases self-reported happiness ratings and even boosts self-confidence. And this is not just because being in clean and tidy natural environments encourages people to take exercise. Neither, it seems, do you have to actually be physically outdoors in these spaces to benefit from these life-enriching effects. Merely having a view over a natural green space is sufficient to influence the rate of healing and the perception of pain. In a famous Science study published in 1984 by Roger S. Ulrich, patients whose recovery room had either a view of a small copse of trees or a brown brick wall were compared, retrospectively, in terms of duration of their stay in hospital and strength of analgesia required to deal with the pain induced by gall bladder surgery performed in the same Pennsylvanian hospital. They found that on average those with the view of a green space spent on average one less day in hospital and required much fewer moderate or strong doses of pain killers compared to those with a view of the brick wall.

Getting out in green spaces is good for your mood AND your health (image courtesy of Nuttakit)

Numerous studies have been conducted since to try to establish what aspects of the natural environment have the strongest benefits to our wellbeing. Virgnia I Lohr, of Washington State University, describes studies suggesting that bright green colours synonymous with luscious vegetation make us feel happier than light greens and yellows that could indicate plant nutrient deficiencies. Furthermore not only does mood improve when we look at trees but we even have a preference for trees with spreading canopies over short and stubby bush like trees typically found in arid areas and tall / narrow trees typically found in areas of very high rainfall. The explanation Lohr offers for these preferences for bright greens and trees with spreading canopies is that such visual stimuli are indicative of conditions suitable for the proliferation of human life. In other words an innate appreciation of such visual characteristics conferred a survival advantage to early humans as they would have been attracted to environments with flourishing plantlife and thus food sources, whilst others would have perished in environments that were either too dry or to wet.

Parks and open spaces are clearly very beneficial in terms of improving health and quality of life. However if it wasn’t for the armies of park staff who clean up after members of the public who routinely leave their litter behind, these green spaces would soon become the last place you would want to spend your spare time. The question is, why do people leave their litter behind for somebody else to clear up? All human behaviour is governed by predictions of reward and punishment. We are subconsciously guided towards behaviours that maximise rewards whilst minimising punishments.

Will people keep Hyde Park tidy when the cleaning staff down their tools for a weekend?

The pleasure pathways of the brain, in particular the nucleus accumbens, are involved in attaching a reward prediction to a certain course of action based on past experience. Drinking water when thirsty or eating food when hungry are examples of behaviours hardwired to produce powerful sensations of pleasure because they help to keep us alive. However the sense of pleasure that people get from putting rubbish in the bin is not innate, like drinking and eating, but instead it must be learned. Nonetheless, even in the absence of a sense of reward from putting rubbish in the bin, if littering is consistently punished then that too can steer people away from anti-social and towards pro-social behaviours. Whilst most parents are still apt to discipline their children for littering, which provides valuable experience of the punishments that follow such anti-social behaviour, parents aren’t always around. In the past adults felt at liberty to scold, or even physically punish, any child that they happened to see dropping litter, but in the modern climate of political correctness this is becoming a thing of the past. Young people no longer learn that punishment reliably follows the act of dropping litter and so their brains do not generate the sense of discomfort, anxiety or unease (generated by the anterior insula) that would precede acts of anti-social behaviour that they know through experience is likely to be punished. So in the absence of any negative emotions associated with the act of littering, nor positive emotions associated with the act of putting litter in the bin, rubbish ends up being lobbed around willy nilly, even when a bin is conveniently located just a few steps away.

When children are brought up with a strong sense of social responsibility then in later life they may get sensations of what might be called “righteous” pleasure from doing the “right thing.” The point is that to get a feeling of satisfaction from performing pro-social behaviours you must have been trained over prolonged periods of time by parents, carers, teachers and/or peers in order to get a kick out of it. If society wants to encourage pro-social behaviours we’ve either got to praise young people more for putting litter in the bin, or make them very uncomfortable when they just drop it for someone else to deal with.

A fascinating study, again from the journal Science (Keizer et al, 2008), indicates that evidence of other people’s antisocial behaviour can make others more likely to be antisocial themselves. This would suggest that the problem with litter goes beyond just rubbish on the streets and in our parks. In one of their experiments they demonstrated that environments in which anti-social behaviour was evident, e.g. litter strewn around on the pavement, graffitti sprayed on the walls or fire crackers set off in the background, not only makes people more likely to litter themselves, but also to commit more serious anti-social behaviours like theft. It seems that people modulate their own behaviour according to cues regarding the degree of anti-social behaviours committed by others.

It is for this reason that Dr Jack predicted that whilst Hyde Park is pristine and clean people will be (slightly) more likely to put their rubbish in the bin. However as the rubbish builds up people will probably become more and more likely to leave their rubbish behind. Furthermore, based on the findings of Keizer and colleagues, the more the rubbish builds up, the more likely people will be to commit other forms of anti-social behaviour. To find out if Jack’s predictions were right, tune into BBC1 tonight at 7pm.

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