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?

Following on from Dr Jack's "Aging Gracefully" item on ITV's THIS MORNING on Fri 12th Aug 2011

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

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.”

In addition to these weekly brainposts you can also catch Dr Jack’s daily #braintweet by following him on Twitter.

Elderly people who do not suffer with Alzheimer's tend to exercise regularly, eat healthily, seek mental stimulation, are proactively engaged in a varied social life and are well integrated into their community. These lifestyle choices do not guarantee to keep dementia at bay, but it sure as hell can't hurt to try

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.

As Alzheimer's progresses brain cells are gradually killed causing brain regions to shrink and the gaps between them to consequently enlarge

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.

Alzheimer's disease involves plaques accumulating around the neural called "axons" that allow communication between different brain areas

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

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.

LANGUAGES

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.

FUTURE TREATMENTS

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

Dr Jack’s first appearance was on Mon 13th June covering the topic of how to improve your memory

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 13^th 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!

Academic credentials:

• 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.

Older brain on the left, younger brain on the right

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.

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