As we progress through life we inevitably find ourselves becoming increasingly forgetful. It is not as if bouts of forgetfulness never occurred when we were younger. It’s just that it begins to happen more and more frequently – to the point where it becomes much more noticeable; even troublesome . From our mid-twenties onwards we lose more neurons (brain wires) and synapses (connections between the brain wires) than we build. The long term end point of this perfectly natural, gradual process of brain aging is dementia. By which I mean if we all lived to the impossibly grand old age of 200, every single one of us would have developed dementia of one description or another along the way. In reality very few of us will even make it to the grand old age of 100, let alone 200. Of those that do, not everyone will have become plunged into the amnesic fog of dementia. So what is the difference between individuals that do and don’t develop dementia well into their senior years? Is it blind luck? Or is there something we can do to lengthen our dementia-free status?
This brainpost complements Dr Jack’s recent appearance on ITV1 on Fri 12th August 2011. It’s tricky to do such an important brain topic as AGING GRACEFULLY justice in just a 10 min slot on THIS MORNING (ITV’s flagship live daytime magazine show in the UK). Talking openly and honestly about highly emotive topics like Alzheimer’s disease, and dementia in general, is a very delicate matter. Given the prevailing time pressures of live television and the quick/punchy explanations that it requires, there is always the potential to be misunderstood. This means that really hot topics must occasionally be left out in case they have the unintended effect of causing undue anxiety as opposed to the specific intention: inspiring the public with what we can do to hang onto our marbles well into old age. This brainpost reveals a new breakthrough in our understanding of Alzheimer’s disease, deemed too risky to mention on live television in case it was misconstrued, but which may one day be instrumental in keeping dementia at bay in each and every one of us.
COLUMBO’S DEMISE FLAGS MECHANISM FOR ACCELERATED DEMENTIA
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?
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.”
In addition to these weekly brainposts you can also catch Dr Jack’s daily #braintweet by following him on Twitter.
Contrast the lifestyles of people in their seventies who do and do not suffer from Alzheimer’s disease and clues about how to keep your brain ticking over nicely, well into old age, jump right out at you. Those who do not suffer with this dreaded disease tend to have been more committed to a regular exercise regime throughout their later years; hitting it as hard as their inevitable physical infirmities would allow (TOP TIP: Tai Chi is an excellent example of a low impact physical exercise which improves strength and flexibility at any age. It requires no equipment and can be practiced wherever you happen to be). They tend to have been more engaged in a wider array of social activities. They tend to have been careful with their diet in the long term, favouring a healthy Meditteranean-style diet (see below for more) over a typical modern Western diet (often high in saturated fats and sugars). They also tend to have been more proactively involved with their local community and more motivated to seek regular mental stimulation. People are now being advised to adopt a variety of brain-healthy habits if they wish to reduce the likelihood of developing cognitive deficits that the progression of Alzheimer’s disease can, but does not always, induce.
Alzheimer’s disease is the most common of the many different types of dementia, affecting 10% of those over 65 and almost 50% of people over the age of 85 (Evans et al, 1989). Dementia describes a syndrome that involves progressive cognitive decline occurring at an accelerated pace compared to the very gradual loss of mental faculties associated with normal aging. Dementia can involve the deterioration of reasoning, judgement, thinking, mood control, language, understanding and, most famously of all, memory. Colloquially-speaking, Alzheimer’s disease is an almighty metabolic cock-up: a brain protein (beta-amyloid) is not constructed properly due to a misprint in the genetic recipe, causing it to form tiny sticky clumps (plaques) that develop between brain cells, preventing them from communicating with each other properly and eventually killing them off entirely. To make matters worse neurofibrillary tangles accumulate within brain cells, which also ultimately leads to cell death.
Depending upon which brain structures these plaques form in, different mental functions can be disturbed. For instance, a brain structure that typically gets more than its fair share of amyloid plaques and neurofibrillary tangles in Alzheimer’s is the hippocampus. As I’ve described in a previous brainpost this brain structure is critical for the formation of memories and so when its function is compromised by the plaques and tangles of Alzheimer’s, people can become extremely forgetful.
To date, scientific research has yet to come up with a treatment to stop the formation of these amyloid plaques and neurofibrillary tangles, but there is evidence that drug treatments designed to boost the cholinergic neurotransmitter system can make symptoms less severe. Furthermore and extensive body of studies has gradually accumulated over the past 20 years to indicate that some people are able to tolerate the disruption caused by these plaques better than others (e.g. Katzman et al, 1988). The Katzman study described individuals who had shown no cognitive impairment whatsoever in life, yet post-mortem examination of their brains revealed that telltale signs of Alzheimer’s disease (the plaques and tangles) which had progressed to a considerable degree. This disparity begs the question: if two people’s brains are affected by the same degree of plaque damage, why does one continue to enjoy normal mental faculties, whilst the other suffers severe impairments to their memory, thinking and mood? The concept of “cognitive reserve” was introduced to describe brains which seemed to be able to compensate for the damage done by Alzheimer’s, presumably by using other brain networks not affected by the metabolic damage to take over certain cognitive tasks.
A separate study, this time involving 593 individuals in New York over the age of 60 and on an “at risk of dementia” register, concluded that “increased educational and occupational attainment may reduce the risk” of developing Alzheimer’s disease. A more recent study conducted in the UK concluded that cognitive reserve is almost entirely mediated by childhood cognitive ability and educational attainment, whilst whether people had successful careers or not had very little influence. So does this mean that the only way to “plaque-proof” yourself is to study hard at school and stay in education for as long as possible? Well, yes and no. Yes – in the sense that this certainly seems to protect you from the ravages of amyloid plaque buildup. No – because there ARE things you can do to build up your cognitive reserve in later life, they just have nothing to do with what you do for a living and how good you are at it.
Diet may well influence the rate at which Alzheimer’s disease progresses, probably due to the negative influence of a modern Western diet on the brain’s blood vessels. In a recent article, prominent Alzheimer’s researcher Dr Scarmeas describes a study providing evidence that a traditional Meditteranean diet – characterised by lots of fish, unsaturated fats, vegetables, fruit and cereals – seems to protect against the development of Alzheimer’s disease. In a different study which used a mouse model of the disease it was suggested that coffee may help to slow the progress of Alzheimer’s disease by preventing build up of amyloid plaques.
A recent NYT article describes research into bilingual people who seem to develop the symptoms of Alzheimer’s on average 5 or 6 years later than those who speak only one language. This suggests that the cognitive demands of regularly switching between two or more languages may delay the onset of Alzheimer’s. Although this has yet to be proven, it is thought that speaking two languages may increase cognitive reserve by improving the function of prefrontal brain areas involved in executive control. Executive control involves mental functions like holding relevant information in working memory whilst ignoring irrelevant distractions, as well as other faculties relating to problem solving, planning and decision making.
In the not-so-distant future it may be possible to replace brain cells damaged by the abberent metabolic processes of Alzheimer’s with fresh ones created from a person’s own skin cells. Other recent research has suggested that the amyloid plaques might cause memory problems by attaching to certain important neurotransmitters, and that drugs preventing this from happening may help to ease the symptoms of memory loss associated with Alzheimer’s disease. In light of the importance of early intervention to catch the disease before it causes too much damage new scanning techniques have already been developed to spot the disease before it induces any clinical deficits.
A variety of lifestyle changes can build up cognitive reserve, helping to keep dementia at bay and improving quality of life to boot!
In addition to these fortnightly brainposts you can also get DrJack’s daily #braintweet by following him on twitter.
Dr Jack will be MAKING YOUR BRAIN BETTER FOR LONGER live on ITV1’s THIS MORNING
Over the summer I’ll be making a series of contributions to ITV’s THIS MORNING. The aim is to get the nation interested in how their brains work and ultimately to help YOU get the most out of YOUR brain. I’ll offer easy-to-follow advice on how to get your brain firing on all cylinders each and every day.
I’ll be answering the questions that YOU want answered. Is your brain not what it used to be? Want to know what you can do about it? Bad with money? Ever wondered why you can’t kick your habits? Ever worry about your children’s development? You can either get in touch with your questions directly by clicking here, or get in touch with THIS MORNING via The Hub.
Topics I’ll be covering in detail will range from money management to memory, from love to hate, from happiness to sorrow, and all the way from child development to holding onto your marbles in old age. You most definitely CAN teach an old dog new tricks and it is never too late to start getting more out of your brain!
Each item will kick off with a discussion with Phillip Schofield and Co. on the sofa to explore ways in which they feel their own brains’ work well and not-so-well. We’ll then be asking members of the public to participate in experiments live in the studio. And we’ll meet some extraordinary people who’ll either demonstrate some amazing abilities or some shocking disabilities. Each item will be packed with useful tips, nudges and strategies for optimising your brain function. So, each week, you’ll be able to put my advice to the test to see how it can benefit your life by boosting your brain power.
Most people would agree that their memories are far from perfect. So, on Monday 13th June 2011, I’ll be showing you what part of your brain creates a MEMORY for people, places, facts and faces. I’ll be putting some members of the public through their paces to see how much information a noraml “working” memory can hold. You’ll even be able to join in the fun and play along at home. I’ll reveal a classic memory trick that is virtually guaranteed to boost anyone’s memory for lists of facts or any other kind of information you might need to remember.
So tune into ITV1 from 10:30-12:30 and SORT YOUR BRAIN OUT!
- Jack has studied Brain Biology for nearly 20 years
- Jack has a First Class batchelor’s degree in Neuroscience from The University Of Nottingham
- Jack earned his PhD in the Laboratory of Neurobiology at University College London
- Last year, Jack published a paper in the prestigious Journal of Neuroscience describing human brain scanning experiments that investigated multisensory perception; carried out during a post-doc at the Max Planck Institute for Biological Cybernetics
- Despite Jack’s extensive knowledge about the human brain, he is NOT medically qualified and so will not be able to answer questions relating to medical care.
From adolescence onwards we all begin to lose brain cells. As a consequence our brains gradually and inexorably shrink (compare the “old” brain on the left to the “young” brain on the right). In fact by the age of 80 your brain will occupy 15% less of the space within your skull than in the prime of life. Yet over the course of adulthood, as our brains are losing more and more cells, our knowledge and repertoire of skills nonetheless continues to grow as we accumulate more and more experience. How is this possible? Well, despite the incremental decrease in quantity of brain cells over the years connections between neuronal networks that are in regular and intensive communication with each other are selectively reinforced. This enables increased efficiency in execution of the mental processes that those networks support. Hence we can do more with less as we age. Sadly, for all of us, there will always come a time when the degree of brain cell loss is such that mental function begins to decline. In other words, if we all could live forever, dementia will inevitably strike at some point in time.
Although we cannot halt the process of grey matter loss completely, the good news is that we can slow down its progression. This month a study conducted at the University of Pittsburgh and published in the journal “Neurology” describes the influence of regular exercise on the rate of reduction of brain volume and cognitive function in 299 elderly individuals.
It was observed that those individuals of this group of average age 78 who walked in excess of 6 miles per week had a significantly reduced rate of grey matter loss and consequently a lesser degree of cognitive decline. The greater the distance walked each week, the smaller the reduction in volume over a 9 year period within their frontal lobe, occipital lobe, entorhinal cortex and critically, in the hippocampus. My post last month described the vital role that the hippocampus plays in the creation and recall of long term memories.
This begs the question – how and why does exercise slow down the rate at which grey matter shrinks? An exciting possibility is that all that walking might actually increase the rate at which new brain cells are created; a process known as neurogenesis. This boost in the creation of new brain cells might help to compensate for the loss of old brain cells. Evidence to support this hypothesis comes from research conducted over a decade ago suggesting, in the mouse brain at least, that exercise does indeed increase the rate of neurogenesis.
Exactly why this happens is unclear, but I would propose that, given the hippocampus is heavily involved in navigation, particularly when it comes to flexibility in finding the best route from A to B, it would make sense for physical activity to trigger production of new cells in this brain area. A greater number of hippocampal neurons would presumably support a greater capacity to memorise routes and landmarks encountered whilst exploring the environment. This could feasibly convey a critical survival advantage by helping to prevent people from getting lost. Over the thousands of years of our species evolultion, getting lost was probably an excellent way of deleting oneself from the gene pool and so those with movement-triggered hippocampal neurogenesis may have been more likely to survive.
This seems a plausible (but by no means concrete) account of why older individuals who take regular exercise appear to have more grey matter and superior cognitive function than those who do not. Whatever the true explanation, it seems clear if you want to hang onto your marbles in the long term then it’s probably a good idea to take a regular stroll for the rest of your life.
You can follow Dr Jack’s daily #BrainTweets by clicking here, and pushing the “Follow” button.
Dr Jack Lewis is keen to get people motivated to get the best out of their brains, so has compiled a quick overview of brain training options:
Brain teasers are good for you. Brain teasers include word games, number puzzles, spot the difference, Where’s Wally-type games, attention directing or splitting challenges, general knowledges quizes and so on. Brain training simply involves perfoming various different brain teasers on a regular basis. Your brain constantly adapts to serve you better. The more often you perform a certain mental function the more the brain will do to make changes so that the next time you do it, you can perform it slightly faster, with a greater degree of success and more efficiently.
How do we know that practice increases the connections between different brain areas? Two brain imaging studies have demonstrated that when people practice a skill very hard for prolongued periods of time despite the fact that the changes happen at the ultramicroscopic level of the synapses where two brain cells meet the net effect of billions of these changes occuring over many months is that the grey matter gets larger in the part of the brain responsible for that function. The part of the brain that controls hand movements is significantly larger in professional string and keyboard musicians than non-musicians because of all the training they have done over the years to manipulate their instruments with split second precision. Another brain region, the hippocampus, creates and recalls memories particularly for geographical locations and is significantly larger in the brains of London Cabbies – who navigate around their city based on a sound KNOWLEDGE of every landmark, road and bridge – than in the brains of bus drivers – who simply drive the same route over and over again.
The synapses connecting various different groups of brain cells together that are responsible for perfoming a certain task, say a crossword for instance, are strengthened each time to try to solve the puzzle in order that they can function slightly more efficiently next time round. If you do the crossword every day, then the net effect of many slight overnight adjustments to the brain areas involved in searching your memory for suitable words that have a certain meaning, a certain number of letters and specific letters in at certain positions within the word, become noticably better after just a few days. The same goes for number puzzles. Or games that involve prolonged concentration. Or the ability to recall trivia when it becomes relevant to conversation.
We all know that practice makes perfect and the strengthening of connections between the relevant brain areas to enable more efficient communication between them is the reason why. Of course getting good at doing crosswords is not particularly useful in its own right, but the point is that once you become good at recalling suitable words for the sake of the crossword, you will also find it easier and quicker to bring the appropriate word to mind during conversation or when creating written documents – and that can be extremely useful.
There are numerous websites that have compiled a large variety of different puzzles (http://www.brainbashers.com/puzzles.asp) and various others where you can try out electronic versions of classic physical puzzles like the Tower of Hanoi (http://www.mazeworks.com/hanoi/index.htm). However these all pale into comparison next to custom-designed brain training games such as those available at Lumosity (www.lumosity.com), which have not only the advantage of a much more aesthetically-pleasing look and feel of games that are genuinely fun and engaging to play, but also as you have to log in to play (they offer a free 30 day trial) you can keep track of how your performances improve over time.
Nintendo DS were the first console manufacturer to produce and market games with the aim of improving brain function which all started with the release of Dr Kawashima’s Brain Training in 2005. This predominantly involes some quite predictable tasks like the Sudoku number puzzles, simple rapid-fire arithmetic, but also some unexpected treats like the Stroop Test (naming the colour of the font ignoring the meaning of the word which can be tricky when the word RED is written in blue font!) which take advantage of some pretty nifty voice processing software. I must admit I found myself thinking “can I really speak to this machine?”
The effect of the advertising campaign that accompanied the release of this game was quite profound as it not only encouraged everyday consumers to purchase Nintendo’s products, but more importantly sent out the message that the brain is something that you can do something pro-active to improve; a concept that has been long-accepted to be the case in children but the mantra “you can’t teach an old dog new tricks” meant that this was rarely considered to be applicable in adults. Such a message is particularly enticing for people entering into old age, for whom the prospect of holding onto their marbles for as long as possible is extremely desirable and thus motivating. In this regard the key thing to remember is that, as far as the brain is concerned, it’s a simple matter of use it or lose it. Exercising brain areas involved in problem-solving by tackling word games, logical reasoning problems, memory challenges and number puzzles keeps such mental faculties in tip-top condition. If you don’t continue to use these mental abilities then they will fall into disrepair because the brain receives no indication that connections between appropriate areas should be maintained and reinforced. The upshot: it is never too late to improve your mental fitness. By emulating the lifestyles of individuals enjoying a healthy brain in their 80s and 90s, who have regular social interaction, cards games, read extensively, stay physically active and challenge themselves daily with various puzzles and quizes, the odds of being afflicted by Alzheimer’s disease are reduced by 25%.