How often were you urged to eat up your greens as a child? In my childhood this was a mantra uttered on a weekly basis. At least. I don’t know where my mum and dad got the idea that leafy green vegetables might be good for the health but, according to a recently published study, it turns out they may have been bang on the money. It never ceases to amaze me how often conventional wisdom ends up being proven true.

A study conducted by Martha Morris and colleagues at Tufts University in Boston and Rush University in Chicago, published in January of this year in the journal Neurology detailed a prospective study of nearly a thousand participants who were followed across a period of ~5 years during which they periodically filled questionnaires about the food they ate and took a cognitive assessment. These individuals were aged 58 and upwards, all the way up to 99 years old. Analysis of the data suggested that: the more often leafy green vegetables were consumed, the slower the rate of cognitive decline.

Those who ate at least one serving of greens per day achieved scores on the cognitive assessments equivalent to those 11 years younger. So it seems that greens don’t just help youngsters grow up into strong and healthy adults, but they can even help us hold onto our marbles during the post-retirement years.

This study also tried to establish which of the many ingredients in the leafy greens might be responsible for these impressive cognitive benefits. Greens rich in folate, phylloquinone (aka vitamin K), lutein and kaempferol all seemed to make a big difference, as did alpha-tocopherol, albeit to a lesser degree. Let’s dig a little deeper into which vegetables contain these various goodies so you can start incorporating them into your diet pronto.

Folate is found not just in dark leafy greens like spinach, collard greens and romaine lettuce, but also asparagus, avocado, broccoli, beans, peas, lentils, cauliflower, brussel sprouts, beetroot, berries (strawberries > rasberries) and citrus fruits.

Similarly, Vitamin K is found in plentiful quantities in leafy greens like spinach and kale, but also in basil (get your pesto on), spring onions, cabbage, pak choi, chili (hooray!), leeks, pickled cucumber, olive oil and okra (aka ladies’ fingers).

There’s plenty of lutein in egg yolk, sweetcorn, kiwi fruit, grapes, orange juice and courgette, as well as greens like spinach, kale and lettuce.

As for kampferol, there’s a huge quantity in capers per 100g relative to that found in kale, and a good dose in dill, cress, chives and broccoli. That said most people will find it an easier and more appetising experience to eat 100g of kale or broccoli, than the same mass of capers, dill, cress or chives.

The take away message here is that there’s nothing magical about the leafy greens in terms of the chemical ingredients that, once absorbed into the body and brain, lead to cognitive benefits. They do, however, serve to simplify matters. Rather than struggling to recall which of these nutritional goodies are found in which fruits, vegetables and pulses, by making sure you get a good dose of greens on a daily basis, you can be pretty sure that you’re getting most of the vitamins and minerals that will keep your brain ticking over nicely.

For most of the twentieth century, in the UK at least, as people progressed through their sixties their bodies generally started showing the typical signs of ageing. By the time they hit 70 they would typically find themselves frail, wrinkled and stooped. When my grandparents were in their sixties they looked very old, so I had assumed this process was an inexorable fact of life. Yet this has not happened as my parents have progressed through their sixties. Rather than the passage of the years stripping the youth from my parents bodies, if anything they seem only to get fitter and stronger; in body and mind. They are in their mid-sixties, yet my dad’s six pack is better than mine and my mum’s musculature is in better shape than when she was in her twenties. And she’s still razor sharp when it comes to correcting my mispronunciations and misspellings. This begs the question: what exactly have they been doing so right that previous generations seemed to get so wrong?

I’ve been digging around in the science literature to find some clues as to whether people really are ageing better these days in terms of body as well as brain. If so, I wanted to know what lifestyle choices can make the difference between vigour and decrepitude. Is down to a better diet? My parents certainly eat very healthily. A meal at their place invariably involves lean meat or oily fish with plenty of veg ever since it emerged that a Mediterranean-style diet is associated with better health. Or could it simply be down to levels of air pollution? When my grandparents were middle-aged we were still happily pumping CFCs from every aerosol can out into the atmosphere in such large quantities that there was a huge hole in the ozone layer (happily since CFCs were banned this situation seems to have improved) and all the petrol we put into our cars contained lead that was then pumped out of exhaust pipes on every road across the nation (which is no longer the case). My parents also keep very active both physically and mentally, my grandparents did not, so another possibility is that their physical fitness and/or regular engagement with activities that keep them mentally sharp could play a role.

A recent review paper by Luis Bettio and colleagues at the University of Victoria in Canada outlined the various factors known to accelerate cognitive decline. Cognitive decline involves problems with the ability to recall details of events, where things are in space, holding several pieces of information in mind simultaneously, maintaining focus and noticing relevant sensory cues (e.g. keeping track of other cars in peripheral vision while driving). All these functions rely heavily on the hippocampus. This structure, which has been mentioned in several previous blogs, is a seahorse-shaped hub of densely-packed neurons that create and retrieve memories, enable us to navigate our surroundings and – if Google’s DeepMind is to be believed – may even play a critical role in imagining what will happen in the future. Bettio et al highlight the roles of education, intelligence and mental stimulation in helping to build cognitive reserve and resilience, but a recent study by Tucker and colleagues, published earlier this year (2017) in the journal Preventative Medicine, suggests that regular physical exercise could be key.

The Tucker study involved taking measurements from 5,823 randomly selected people and logging their physical activity levels. They showed that the telomeres – a string of DNA bases positioned at the end of each chromosome, in this study the chromosomes of their white blood cells – were significantly longer in those who exercise regularly. Not only that, the more active the people were, the longer their telomeres. The significance of this is that telomere shortening has long been associated with gradual deterioriation of our organs and tissues during aging. The exciting conclusion here is that keeping physically activity and taking more strenuous exercise on a regular basis actually seems to preserve telomere length. They even managed to put a figure on it. The High Activity group had reduced their biological aging by 9 years compared to the Sedentary group and by 8.8 years compared to the Low Activity group.

These aren’t my parents (in case you wondered)

As much as a healthy diet and reductions in air pollution probably helped in general, it seems that the key difference in the rate at which my parents aged in comparison to my grandparents is largely due to the telomere-preserving influence of their active lifestyle (regular walks and dancing classes) and biweekly visits to the gym (to do body pump and yoga). So, if you want to help your middle-aged people age more gracefully, then it’s time to get them down to the gym or out on long walks, on a regular basis.

In addition to these monthly blogs, I regularly post brain news on my twitter account (@drjacklewis), do a fortnightly science podcast (Geek Chic’s Weird Science) and present a TV series called Secrets of the Brain on Insight TV (Sky channel 564).

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?

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.

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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