Year: 2023

The idea was simple. Recruit hundreds of people in their 80s and 90s, equip them with fitness trackers, and monitor their physical activity. Then, when the participants died, collect their brains and examine the tissue. Is there evidence, lurking in the tissue, that exercise benefits the brain?

The results, from a 2022 collaboration between the University of California in San Francisco and the University of British Columbia, were striking. Physical exercise, late in life, seemed to protect the ageing connections between brain cells – the synapses where memories are made. The work, if backed up by further studies, could see exercise, and potentially drugs that mimic biochemical aspects of activity – prescribed to help slow the onset of dementia.

“We know there is a 30{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f}-80{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} reduced risk of dementia in people who exercise,” says Kaitlin Casaletto, the lead author on the study and an assistant professor in neurology at UCSF. “My question was, wouldn’t it be cool if we could figure out exactly how this is happening? If we could identify some of the mechanisms of exercise for brain health? These are potential therapeutic targets we can bottle.”

A small mountain of work has linked physical exercise to better brain health and lower risk of dementia in older age. One recent study of nearly 80,000 people in the UK found that the risk of dementia was halved in people who reached the goal of 10,000 steps a day. But much is still unclear. Part of the observed benefit could be down to people with healthier brains simply exercising more. While there are definite benefits to be had from exercise – greater blood flow to the brain, better cardiovascular health, lower blood pressure, less obesity and diabetes – there is still plenty to nail down.

Dementia is the number one killer in the UK, with the disorder affecting about 900,000 people. Most cases, about two-thirds, are driven by Alzheimer’s disease, but it is far from the only cause. Other forms, namely vascular dementia, dementia with Lewy bodies, and frontotemporal dementia, arise from other processes. Whatever the cause, the steady destruction of brain cells erodes memory, thinking, movement and personality. In old age, dementia can be several of these conditions at once.

Some of the highest rates of dementia are found in developed countries with older populations. In Germany, Italy and Japan, more than 20 in every 1,000 people have dementia compared with fewer than nine per 1,000 in proportionally younger countries including Mexico, Turkey and South Africa. The UK sits in the middle. Indigenous groups in the Amazon have some of the lowest rates. In one recent study, researchers confirmed only six cases among 604 Bolivian Tsimane and Moseten people aged 60 and over, suggesting that lifelong physical activity and healthier preindustrial diets substantially reduce the risk. Over the next three decades, global dementia is due to rise substantially, particularly in north Africa, the Middle East and eastern sub-Saharan Africa, where population growth and ageing will be among the driving forces.

But dementia is not inevitable, nor is it the reward for dodging other fatal conditions. Take all of the risk factors that we as individuals, or nations through their policies, might improve, and potentially 40{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} of cases could be prevented or delayed. We would not eradicate dementia, and many people who did everything to keep their brains healthy would still succumb to the disease. We could, however, dramatically reduce the risk, meaning more years of sound thinking, intact memories and independent living. “That figure, 40{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f}, is an enormous percentage,” says James Rowe, professor of cognitive neurology at the University of Cambridge. “If we had a drug that could cut dementia by 40{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f}, it would be a phenomenal success.”

Our brains change even with healthy ageing. People vary tremendously, but vocabulary often improves past retirement age, while processing speed, the ease of learning new information, cognitive flexibility, and working memory – for example, how many digits of a phone number you can remember – weaken. Learning more slowly in older age is often framed as a negative, but it has its advantages. Young people know so little that learning everything fast makes sense. But older people weigh new information against a lifetime’s learning. Does it fit with what I know to be true? Is it reliable? Does it deserve to be learned? “When you are born, you are fast but know little. When you are old, you are slower but knowledgeable. Which is better? It depends on the situation,” says Rowe.

Dementia is very different to healthy ageing. It is what happens when brain cells are destroyed by disease. A healthy older person can expect a gradual decline in memory and thinking skills, but people with dementia can develop profound problems with memory, judgment, language, concentration and personality. The sharp decline in performance is mirrored by a pronounced shrinkage of the brain.

Last year, researchers at the universities of Cambridge and Pennsylvania stitched together 125,000 brain scans to reveal how the human brain changes from a 15-week-old foetus to a 100-year-old adult. The work was a tour de force. Ultimately, it should allow doctors to assess how a person’s brain is ageing over their lifetime, much as paediatric growth charts allow them to check whether children are developing normally. For example, a person’s brain might be in the 50th centile at age 45, but if it falls significantly on subsequent scans there may be a problem. The researchers already see stark shifts in scans from people diagnosed with Alzheimer’s. “We see those individuals crashing through the centiles,” says Richard Bethlehem, an assistant professor in neuroinformatics at Cambridge.

Because dementia is seen as a problem of old age, this might seem like the time to act. But ageing is a lifelong process: the better the brain ages, the better it can stave off or withstand dementia. “A lot of the seeds of poor brain health, including dementia, are sown well and truly in childhood and then built on through early adult life and middle age,” says Rowe. “The state of our brain health in late life, when we are conventionally worried about dementia, depends on a whole lifespan of lifestyle and activities.”

In 2020, 28 world leading experts published a major report called the Lancet Commission on dementia. It identifies a dozen “potentially modifiable” factors that affect our risk of developing dementia. Which matters most depends on age. In youth, a good education makes an enormous difference, and benefits brain health for the rest of life. In midlife, not boozing too heavily and controlling blood pressure all come into play. In later life, not smoking, exercising regularly and keeping socially engaged stand out.

How these help to prevent dementia is not always straightforward. A good education doesn’t happen in a vacuum. It can reflect a child’s circumstances: their home environment, household income and expectations all play a part in sculpting the brain. Armed with a good education, people are better equipped to look after themselves. But education seems to act directly on the brain too, creating what researchers call cognitive reserve and resilience. Build up brain capacity early in life and that reserve becomes a shield against future damage. Likewise, education boosts resilience, the brain’s ability to compensate when diseases like Alzheimer’s arise. The impact can be striking. “For people with a very high education, when you look at the brain postmortem, they can have a lot of neuropathology without having had any symptoms,” says Gill Livingston, professor of psychiatry of older people at University College London and lead author of the Lancet report. In short, the disease is there, but the brain can withstand it, at least to the point that obvious symptoms never manifest.

According to the Lancet Commission, poor education accounts for 7{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} of dementia worldwide. But the benefits of stretching one’s brain don’t end in youth. People who do cognitively challenging jobs have a lower risk of dementia, too, regardless of their education. As the Lancet report puts it: “The use it or lose it hypothesis suggests that mental activity, in general, might improve cognitive function.” The impact of other brain-stretching activities is far from clear, however. Despite a flurry of brain training programmes being developed to boost cognitive skills, there is no good evidence that people improve at anything apart from the particular task they practise.

One message that runs through all the research on dementia prevention is that a healthy lifestyle helps. Diet is important: you cannot grow a good brain without good nutrition, and a healthy diet helps to maintain it. A recent meta-analysis of studies, involving nearly 35,000 people, found that strict adherence to the Mediterranean diet was associated with a 21{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} lower risk of cognitive disorders and a 40{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} lower risk of Alzheimer’s. Whether specific nutrients and compounds are directly beneficial to the brain is the focus of intensive research, but healthy diets are encouraged regardless, because they reduce risks caused by other disorders, such as high blood pressure, poor vascular health, obesity and diabetes.

Which single intervention could reduce dementia risk the most? The answer is one that even some researchers find surprising: preventing hearing loss. Globally, hearing impairment is believed to account for about 8{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} of dementia. Hearing loss means less stimulation for the brain, but also more social isolation for the individual. The brain appears to shrink more rapidly, or at least the temporal lobes, which focus on sound processing, emotions and memories. What’s striking is that the link between hearing loss and dementia is all but absent if people wear hearing aids. Livingston believes this is a huge opportunity. While people with poor eyesight tend to have it corrected, a large proportion of those who cannot hear well either think other people mumble, or are reluctant to wear a hearing aid. Correcting hearing loss as well as we correct poor sight could be a gamechanger, if enacted globally. “I think wearing a hearing aid is still stigmatised,” Livingston says, but she wonders, with more and more people now wearing earbuds, whether that barrier will soon fall too.

The picture emerging from decades of research is that the best protection against dementia comes from building a good brain, keeping it healthy and active, and avoiding too much damage. The latter can happen in seconds or years. Brain injuries, from traffic accidents, military service, falls, or impacts during sports such as boxing, rugby and horse riding, all increase the risk of dementia. So does the sustained damage that comes with smoking, air pollution and excessive alcohol intake – over 21 units a week. Brain injuries are thought to account for about 3{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} of dementia, with heavy drinking and smoking making up 1{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} and 5{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} respectively. Air pollution accounts for around 1{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} of dementia.

As might be expected, some experts in the field already take steps to reduce their risk. Because it is unclear which exercises are most protective, Dr Casaletto does weekly yoga, but she also jogs and includes high-intensity sprints in her routine. She eats healthily, maximising the vegetables, whole grains, olive oil, fish and legumes of the Mediterranean diet. Then there is the cognitive component. She tries to stay socially and mentally curious – pushing herself at work, broadening her collaborations, and hanging out with people she wouldn’t normally socialise with. “I think novelty is really important,” she says. “If we are doing the same thing over and over, we are not going to be pushing our brains into forming new connections.”

As part of her own risk-reducing lifestyle, Prof Livingston lifts weights and tries to reach 10,000 steps a day, even though she acknowledges it is “not a magic number”. She reads and writes. And she is wary of the impact of giving up work. “I can see that not being retired keeps you so much more active in lots of ways,” she says. “It might make me less likely to retire. Though I do hope that if I get to the stage when I ought to because I can’t function, that my colleagues will tactfully let me know.”

Four changes to make now

Dementia research, like all research, comes with caveats. Most studies cannot prove that doing X instead of Y helps fend off dementia. More commonly, scientists find associations, such as older people who exercise develop less dementia. But there is always the risk of reverse causation. What if people prone to dementia simply exercise less? Whether, and to what extent, exercise protects people’s brains can take some unpicking. The bottom line on whether this or that action keeps dementia at bay is rarely clear cut. Often the picture emerges with time, as evidence builds from different directions. But these are some things that you can do to help reduce the risk.

Get sweaty

Keeping physically active matters. By combining the results from multiple studies, scientists find have found time and again that dementia and Alzheimer’s are less common in people who exercise. Sustained exercise in midlife, and possibly later life, appears to protect against dementia. A mix of aerobic exercise and strength training seems most effective. For aerobic exercise, breaking into a sweat at least once a week or doing more than 150 minutes of moderate to vigorous exercise each week have both been shown to be protective. How exercise helps is a focus of ongoing research, but at the least, it can reduce the risk of obesity and diabetes while boosting cardiovascular fitness, all of which lower dementia risk. Other gains can be had from quitting smoking and not drinking too much alcohol.

Use a hearing aid (if you need one)

Less intuitive than mental and physical fitness is the impact of hearing loss. Poor hearing in middle age is thought to be one of the most significant drivers of dementia that people can act on. The mechanisms are still being teased out, but brain scans have linked poor hearing to faster brain shrinkage, itself a driver of dementia. Hearing loss also drives up social isolation, which compounds the problem, as people withdraw from social gatherings and the conversations they entail. But there is good news emerging: the marked declines seen in people with hearing impairments are not as dramatic in people who wear hearing aids, suggesting that correcting the problem can help keep dementia at bay.

Keep on learning

A good chunk of people’s resilience to dementia comes from early life education. But even after school or university, keeping the brain mentally engaged matters. It is important for the brain to be making new connections. This means challenging yourself mentally, setting your brain to work on varied, unfamiliar and cognitively complex issues. A mentally challenging job may help, but so should lifelong learning, engaging hobbies and keeping socially active, especially if you mixing with people you wouldn’t normally hang out with. Being more sociable in your 50s and 60s is linked to better cognitive performance and a lower risk of dementia later in life, perhaps because it gets people using their memory and language skills. Keeping the brain active builds “cognitive reserve”, researchers say, meaning the brain is better able to cope as the pathologies that drive dementia take hold.

Prioritise dental hygiene

One of the more speculative ideas on how to reduce dementia risk comes from research into bugs in the mouth. A recent study in the US found that people with gum disease and mouth infections were more likely to develop Alzheimer’s, the most common cause of dementia. Work is now under way to check whether bacteria such as Porphyromonas gingivalis help drive the condition, or simply proliferate in people in the early stages of dementia. If bacteria raise the risk, there will be even more reason to properly brush and floss twice a day.