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Defying Dementia

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Defying Dementia

WHEN you have dementia, the thought processes and memories you once took for granted can shift and vanish, even as you reach for them. It can be like going to fetch something from a familiar cupboard, but “you open the cupboard and there’s nothing there,” says Sube Banerjee, director of the Centre for Dementia Studies at the University of Brighton, UK. “You know it should be there but it’s not.” If that sounds scary, think about the prospect of not being able to recognise your own partner or child.

It’s not without reason that dementia is the disease people over 60 fear the most. More than a third of people in the UK have a family member or friend with dementia, and it’s a similar story elsewhere in the developed world. Globally, 1 in 20 people over 60 lives with the condition. And thanks to our longer lifespans, those numbers are expected to soar. The figures are alarming, as are the stories of people who have experienced dementia.

But these testimonies help us understand it. And knowledge is power. Dementia is not an inescapable result of ageing, and we are making inroads against it. There may not yet be a cure, but we can do things to help keep it at bay, and hold it in check once it’s struck. Read on to find out how we can wrest back control.

WHAT CAUSES DEMENTIA?

DEMENTIA isn’t inevitable. The human brain can stay sharp well past 100 years of life. Yes, getting older slows us down: parts of the brain associated with memory and executive function shrink, myelin sheaths around our neurons start to erode, slowing down signalling, and arteries narrow diminishing blood supply.

But those things mainly affect speed: when healthy older people are given extra time to perform cognitive tasks, the results are on par with younger folks. In contrast, dementia alters the cognitive playing field. As well as affecting memory, it causes issues with understanding or expressing oneself in language, problems with sensory perception, and disturbances in executive function that can undermine day-to-day independence.

Dementia also isn’t just one thing. “People sometimes use dementia and Alzheimer’s disease interchangeably. But that isn’t correct,” says John Haaga, director of Behavioral and Social Research at the US National Institute on Aging, (see “The different kinds of dementia”). Genes play an important part in many kinds of dementia. If you have a parent or sibling with it, you are more likely to develop it yourself. More than 20 different gene variants are now known to influence susceptibility, (see “Should you test your genes?”).

The various conditions give rise to similar symptoms by different means. Vascular dementia, for instance, can result when cardiovascular disease or a stroke limits blood supply and damages brain tissue. Alzheimer’s disease, the most common cause of dementia, is characterised by a build-up of hard plaques of beta-amyloid protein between brain cells, and tangles of tau protein within them. The amyloid hypothesis, the leading idea for how these plaques drive cognitive decline, suggests that a build-up of plaques causes inflammation in the brain, which spurs development of tau, which disables and then kills brain cells, resulting in memory loss, confusion and other symptoms.

This hypothesis is supported by research in families with early-onset Alzheimer’s, which strikes before age 65; many have gene variants that interfere with the ability to clear amyloid. That is also the mechanism by which a certain variant of the APOE gene that codes for apolipoprotein E – a protein that binds to and affects the clearing of beta-amyloid – can increase risk of Alzheimer’s. Yet, despite the dominance of the amyloid hypothesis, the absolute cause of Alzheimer’s is far from being agreed on. To begin with, autopsies reveal that many people die with a significant amount of amyloid in their brain without ever showing dementia-like symptoms. And promising amyloid-clearing drugs have failed spectacularly in clinical trials involving people with advanced disease, (see “Will we find a cure?”).

Still, most researchers in the field remain convinced that beta-amyloid is central to the Alzheimer’s tale, even if it doesn’t tell the whole story, says Laurie Ryan, programme director for Alzheimer’s disease clinical trials at the US National Institute on Aging. There is also evidence that it may be a kind of “diabetes of the brain”, Ryan says, where the ability to use glucose, our brain’s essential fuel, is impaired. With a condition as complicated as Alzheimer’s, as with other forms of dementia, many different factors probably contribute.

WHY IS ALZHEIMER’S ON THE RISE?

ALZHEIMER’S disease strikes after our reproductive years, so the established thinking is that there has been no evolutionary pressure to weed it out, and its prevalence has risen simply because we are living longer. Things might not be that simple. The “grandmother hypothesis” has it that helping raise your grandchildren boosts the chances your genes will be passed on. So any gene that lets you do this by fending off Alzheimer’s provides an evolutionary edge. Previous research suggested such genes offer protection by enhancing the hormone oestrogen’s anti-inflammatory activity in the brain. Now Molly Fox of the University of California, Los Angeles, has some evidence to support the idea. Her team calculated lifetime oestrogen exposure for 81 women over 70 by looking at onset of puberty, pregnancies, age at menopause and other factors. Each extra month with oestrogen was associated with a 0.5 per cent decrease in Alzheimer’s risk. That suggests changing exposure to the hormone– due to having fewer children, among other things –may be linked to the rise in Alzheimer’s

BEATING BACK DEMENTIA
In the UK, improvements in education and heart health may have helped reduce dementia rates, although women remain more vulnerable – largely because they live longer
BEATING BACK DEMENTIA

WHAT CAN YOU DO TO AVOID DEMENTIA?

THE number of people affected by dementia may be rising, but most specialists say that’s largely because more of us are living longer. Between the late 1980s and 2011, the proportion of people over 65 with dementia actually dropped by 20 per cent in England and Wales. Between 2000 and 2012, dementia rates in that age group dropped by 24 per cent in the US. Similar declines have been reported in other developed countries.

There are two driving factors, says Kenneth Langa at the Michigan Center on the Demography of Aging, who tracked the US trend: a rise in educational attainment and better control of cardiovascular issues. After the second world war, there was an increase in schooling that averaged out to about an extra year of education across the US population.

Research suggests that people with more education, or those who have done things like learn a newlanguage or learn to play amusical instrument,may be resilient tosymptoms of dementia. That doesn’t mean they escape the ravages of vascular dementia or plaques of Alzheimer’s, but theymay cope better with the damage.“By challenging your brain during education, you create a more fit brain that cancompensate for problems that you have as you age,”Langa says. Increased cognitive reserve is thought to help in two ways: boosting the brain’s ability to work around damaged areas, and promoting more efficient processing.

That might also explain why people with more education seem to decline so rapidly: it’s not that Alzheimer’s comes on suddenly, it’s that by the time symptoms manifest the disease may already be quite advanced. As for cardiovascular risk factors, while the prevalence of conditions such as high blood pressure and diabetes has risen over the years, there has also been an increase in treatments that can limit their damage.

But poorer countries haven’t seen such advances. And despite improvements in wealthier nations, the absolute number of dementia cases will probably continue to climb – the decline in prevalence isn’t steep enough to make up for the rising tide of ageing baby boomers, says John Haaga at theUSNational Institute on Aging. “People are living longer – and that’s great. We’re also living with our wits intact for much longer,” Haaga says. “But we can’t deny that we have a much larger population of ageing persons to contend with in the future.”

What’s more, there is not a significant educational attainment difference between 65-year-olds and 25-year-olds today, and metabolic diseases like diabetes are on the rise. That means gains we’ve made may not continue apace. It is also important to acknowledge that much of dementia risk is down to genetics, about 70 per cent in the case of Alzheimer’s disease, says Jonathan Schott of the Dementia Research Centre at University College London. Too often he sees patients lamenting that they didn’t do enough, but sometimes there is only so much you can do. “We know that some people have strong genetic risk factors that can predispose them to some forms of dementia whether

they live a healthy lifestyle or not,” he says. Still, if 30 per cent or more of dementia risk is down to lifestyle and environmental factors, there is an opportunity to make a difference. Maintaining social connections, keeping a healthy diet, exercising regularly, practising good sleep habits and pursuing intellectual challenges may all delay or lessen symptoms of dementia later in life. “Walk, talk and read,” says Langa. And do it now. “These changes have the most effect when they are started earlier in life.” Physical activity may be most critical. Regular exercise not only addresses risk factors such as weight and cardiovascular health, but it increases the creation of brain cells, connections between neurons, and production of nerve growth factors and neurotransmitters, says Arthur Kramer at University of Illinois at Urbana-Champaign. You don’t have to run ultra-marathons to reap the benefits. Just an hour-long walk a few times a week can make a difference.

WHAT ARE THE WARNING SIGNS?

WHEN it comes to memory, all of us get a bit creakier as we age. It’s common to forget the specific word you were searching for, miss the occasional appointment or misplace your car keys. “It happens to all of us,” says Sube Banerjee at the University of Brighton, UK. So when might a memory issue be more than just a little extra creakiness? Because so many things can cause dementia, symptoms and severity can vary greatly, making it difficult to catch the earliest warnings. But common signs include problems with short-term memory, abstract thinking, the ability to focus, visual perception and communication. There’s no reason to be alarmed if you do have the odd “senior” moment. For one thing, people of all ages have differences in memory, says Joseph Masdeu, director of the Nantz National Alzheimer Center at Houston Methodist Hospital in Texas. And as well as slowing down, certain skills shift as we get older. “Multitasking, the ability to deploy attention to multiple things at the same time, becomes more difficult,” says Jason Brandt, director of medical psychology at Johns Hopkins University in Baltimore, Maryland. One warning sign might be the inability to summon a memory even when prompted. With normal ageing, it might take you longer to remember, says Brandt, but at early stages of Alzheimer’s, having more time won’t help because “the information has degraded”. When these types of shifts happen, or memory or cognitive problems begin to interfere with daily life, it’s time to consult a doctor. Healthcare professionals have tools to help catch problems early. To assess patients over 60, most use some version of the mini-mental state exam, which asks simple questions about time and place and is designed to measure cognitive impairment. Doctors may also test working memory by asking people to count backwards from 100 in 7s or remember three unrelated items after a period of time. If you score poorly on these kinds of tests, you should expect to be referred for further testing. For people who want personalised feedback from home, Brandt and his team developed an online tool. It includes a series of memory tests, as well as a questionnaire about different risk factors for dementia. “This enables people to do something in the privacy of their home,” he says. If there is something worrying, it directs you to follow it up with your doctor.

HOW BEST TO CARE FOR SOMEONE WITH DEMENTIA?

THERE are a few drugs to treat the confusion caused by dementia. Some can, for a limited time, help improve memory. But there aren’t yet drugs that offer a cure. Dementia treatment is more about finding the right way to care for a person whose mental faculties are declining. Because it varies so much from person to person, there is no “best practice”plan. Dementia is often thought of as a disorder of memory. But to slow its progression, it may be best to focus on factors that are simply due to ageing – trouble with vision, for instance. “What we do depends on what the most annoying symptoms are,” says June Andrews, a specialist in dementia care and author of Dementia: What you need to know. Simple things like improving the lighting, clearly labelling drawers, avoiding patterned floor surfaces and wallpapers or making sure someone has access to large print books and reading glasses, can make a big difference to how rapidly symptoms progress. “There is not a lot we can do about the pathology,” says Andrews, “but there are masses we can do to reduce the symptoms. And it is the symptoms that are dementia.” To stay well with dementia you need to avoid stress, stay hydrated, exercise, be distracted with interesting things, keep pain under control, avoid constipation and sleep well – among other things, says Andrews. The more you can attend to these needs, the longer someone will be able to maintain a higher quality of life. There are some new strategies being developed – care homes that focus on helping people better engage with their environment and look after themselves, for instance. But there is no definitive research to show one care type is better than another, says Sube Banerjee at the University of Brighton, UK. People often live for a decade or more after a dementia diagnosis, and their needs will be different at different stages. Three key aspects have been shown to improve outcomes. First is increased awareness and understanding of the disorder from the public and medical professionals. Second, diagnosis as early as possible so people can take part in planning their future while they have the capacity to do so. And third is quality of care and support from family. Part of that is ensuring that the caregivers look after themselves too, says Banerjee. Family can be critical to whether a patient will do well, he adds. “There are little miracles happening every day where family members help put the focus on what patients can do rather than what they can’t.”

THE DIFFERENT KINDS OF DEMENTIA
Dementia is not one thing. There are several routes to similar symptoms
THE DIFFERENT KINDS OF DEMENTIA

SHOULD YOU TEST YOUR GENES?

WITH about two dozen genes accounting for 70 per cent of your Alzheimer’s risk – the only kind of dementia we can do genetic tests for – taking a test may seem like a simple choice. But with not cure in sight, what can you do with the results? Having the APOE4 gene variant, for instance, only means you have a higher risk of Alzheimer’s, not that you will get it. Genes associated with early on set Alzheimer’s, such as certain mutations of APP, PSEN1 and PSEN2, are more definitive. But even those with a family history of the disease struggle with whether to get tested. Carol Jennings knew she had a 50 per cent chance of having the faulty APP gene, but didn’t want the test. With no cure, what was the point? Only when symptoms began did she finally get tested. Now Jennings’s two adult children, who may have the same mutation, face that difficult decision. One doesn’t want the test; the other hopes the results can guide future plans. It’s understandable that genetic testing prompts mixed feelings. Today it is mostly useful for identifying candidates for clinical trials, and to help researchers understand the disease and potential treatments, says Laurie Ryan at the US National Institute on Aging. “It can’t tell us anything like, ‘If you have this variant, we need to do this to help you’.”

WHAT IS DEMENTIA LIKE?

WITH so many different causes, each person’s experience of dementia is bound to be unique. But specialists say the best way to understand what it is like for a loved one may simply be to ask. If they have mild to moderate dementia, they should be able to answer. What they say may surprise you.

Stuart Jennings, is the carer for his wife Carol (see “Should you test your genes?”, left), who has advanced Alzheimer’s. He is a chaplain at the University of Warwick, UK. What is it like seeing your wife develop dementia? The best analogy I know is a sandcastle. Little by little bits trickle away. The decline is slow and relentless, but then periodically there are huge falls, and you realise you’ve lost something more – and for good. What did she say it was like for her? She didn’t want to talk about that, she was pragmatic, she talked about what she wanted. “Please keep me clean,” she said. “If you’re struggling, please get me into a good home.” And the most important thing: “Please make sure that my brain is donated.” Now I too have signed up to donate my brain for research – as a healthy control. It’s probably the most powerful expression of our love for each other, that we’ll beat this awful illness, even in death. It’s an act of defiance.

Lorraine Brown,worked as a mental health nurse for 24 years. She has early-onset Alzheimer’s, whichwas diagnosed in 2014. She serves as an ambassador for the Alzheimer’s Society in the UK. Before youwere diagnosed, were there signs? I used to do a lot of bluffing. If I couldn’t recall people’s names, I’d try to catch their eye, or deliberately go and stand near them to ask a question. The symptoms really go unnoticed for up to 10 to 15 years. And in that time, I was slowly changing. I know we all change, but I was losing my personality, myself. When did you know something was wrong? One day I went to a patient’s house in a very familiar area, a stone’s throw from the hospital where Iworked. When I came out, it was as if somebody had placed me in a different town. When I looked around, I couldn’t recognise the buildings, the road markers, any of that. It had all gone.

WILL WE FIND A CURE?

NEWS headlines seem to announce promising new treatments for dementia each month. But while many drugs have helped prevent or reverse dementia-like pathology in animal models, they have so far failed to do so in human clinical trials. With Alzheimer’s,many drugs have focused on clearing excess beta-amyloid from the brain. But several clinical trials have been cancelled because of lacklustre performance. In fact, the medications barely stood a chance of helping the people they were tested on, says Joseph Masdeu at Houston Methodist Hospital in Texas. “The drugs were not given until the participants already had cognitive problems. The damage was already done.” But if given to people when they are unimpaired,many researchers are confident drugs could make a difference. Both beta-amyloid and tau proteins can be seen in brain scans decades before there are cognitive issues (see “What causes dementia?”). That offers a window for intervention. But which individuals should be targeted for these kinds of measures? Anarea of intense research is to identify definitive signs of dementia in the body. Finding an equivalent of cholesterol, a biomarker that, although imperfect, helps doctors under stand who is at risk of heart disease,would be a game-changer. It would allow doctors to screen patients early for potential disease – and decide who would benefit

from different preventive approaches, says Kenneth Langa at the Michigan Center on the Demography of Aging. The lack of progress isn’t for lack of trying. There are studies of families and groups with early-onset Alzheimer’s, the largest of which is known as the Colombia cohort. Teams are feverishly hunting for genetic and environmental factors that affect dementia risk. There are analyses of long-term studies like that tracking a group born in the UK in 1946. There are trials involving people with the APOE4 gene variant, known to increase risk of late-onset Alzheimer’s – particularly in women. And there are efforts to use neuroimaging to identify amyloid build-up ever earlier. Teams are investigating ways to treat inflammation that may cause dementia’s cognitive symptoms after amyloid build-up as well, and focusing on agents that may offer neuroprotection or neuroregeneration. “There are a lot of pieces to this puzzle,” says Laurie Ryan at the National Institute on Aging. “It’s likely there will be different treatments and interventions for different patients if we really want to affect change in the long term.” Langa agrees. “The next 10 to 20 years will be very interesting,” he says. “We can do more to get in there and intervene to decrease the risk and prevalence of dementia. We’re doing the work.”

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