LOOKING TO THE FUTURE

With the numbers of people affected by Alzheimer’s disease set to soar, it’s never been more important to understand this condition, as well as the strategies that can help with early prevention and delaying symptoms.

With the numbers of people affected by Alzheimer’s set to soar, it’s never been more crucial to understand this condition.

Along with the other health issues raised by our ageing population experts have warned of a ‘grey tsunami’, which could see the number of cases of Alzheimer’s disease and other dementias more than double by 2050.

“We estimate around 70,000 people have dementia in New Zealand and that around 60 to 70 per cent of those will have Alzheimer’s disease,” says Catherine Hall, chief executive of Alzheimers New Zealand.

There is no doubt there are enormous challenges ahead, however recently published research is encouraging, potentially paving the way for earlier diagnosis and offering new understandings of Alzheimer’s disease and approaches to treatment. Positive evidence is also coming to light for modifiable risk factors, which The Lancet medical journal says account for 40 per cent of worldwide dementias, and which it suggests could theoretically be prevented or delayed.

WHAT IS ALZHEIMER’S?

The most common form of dementia, Alzheimer’s disease, damages the brain, resulting in impaired memory, thinking and behaviour. It’s named after Dr Alois Alzheimer who, in 1907, noticed changes in the brain tissue of a woman with dementia who had died at the age of 55. During her post-mortem he found shrinkage of the outer layer of the brain and identified ‘tangles’ of fibres and abnormal ‘clumps’ or plaques, now known to be associated with Alzheimer’s disease.

Mostly affecting people over the age of 65, increasing age is the biggest risk factor, with three in 10 people over 85 living with Alzheimer’s disease. Women are affected in greater numbers, partly because they live longer than men. It can occasionally affect people as young as 30 and, when it occurs under the age of 65, it’s referred to as younger-onset Alzheimer’s or younger-onset dementia. Just five to six per cent of Alzheimer’s cases are in the younger-onset age group, and most of these will have the common form of the disease. However, a very small percentage may have the familial form, a rare condition caused by a mutation in one or two genes. The genes identified to date include ApoE4 and presenilin, but the Australian Alzheimer’s Research

Foundation says the presence of a gene in one generation doesn’t automatically mean it will be passed to the next generation. It also points to some evidence that genetic risk may be able to be modified through lifestyle interventions.

ADVANCE WARNING

In the initial stages of Alzheimer’s, the short-term memory is affected and the person can find it hard to learn and retain new information. As the disease progresses longer-term memory is affected and the person may find it difficult to remember people and events from earlier in life.

The early signs of dementia can be subtle and can also be similar to symptoms caused by ageing, infection, vitamin deficiency, metabolic disorders and the side effects of some medications, so it’s important not to assume they’re due to dementia. Some of the early signs include:

• Memory loss that affects day-to-day function

• Difficulty performing familiar tasks

• Confusion about time and place

• Problems with language

• Problems with abstract thinking

• Poor or decreased judgement

• Problems with misplacing things

• Changes in personality or behaviour

• A loss of initiative

If you have any concerns, it’s important to see a GP to get a proper assessment.

There’s no definitive test for Alzheimer’s, but a doctor may make a diagnosis with a detailed medical history and neurological examination, as well as blood and urine tests. A psychiatric assessment, neuropsychological tests, a lumbar puncture and medical imaging can also help form a diagnosis, as well as ruling out other conditions.

PLAQUES AND TANGLES

It’s not yet fully understood what causes Alzheimer’s disease in the majority of people, but is thought to be a combination of age-related changes in the brain, together with genetic, environmental and lifestyle factors.

Beta-amyloid plaques and neurofibrillary tangles in the brain are the two most common hallmarks of the disease. Both are found in the brains of older people who don’t have Alzheimer’s disease, but they are more widespread in those who do.

The plaques build up in the spaces between nerve cells, while the tangles are twisted fibres of a protein called tau that builds up inside cells. Their role in Alzheimer’s disease isn’t yet fully understood, but scientists believe they may block communication between nerve cells and disrupt the processes they need to survive. The death of these cells leads to the memory problems, personality changes and other symptoms associated with Alzheimer’s disease.

As brain cells die the brain begins to shrink, with the outer layer usually affected first. Short-term memory loss is one of the first symptoms, but as the disease progresses, deeper parts of the brain are affected and long-term memory is lost.

The Australian Alzheimer’s Research Foundation says it’s unknown why the plaques and tangles form and it’s also uncertain why beta-amyloid builds up in some people and not in others. However, they also point to vascular issues being strongly connected with the disease, with a strong correlation between cholesterol levels, blood pressure, obesity and the level of beta-amyloid in the blood.

PREVENTION STRATEGIES

A report by The Lancet has identified nine modifiable lifestyle risk factors for dementia, which researchers believed could prevent or delay up to 35 per cent of cases. These include less education, hypertension, hearing impairment, smoking, obesity, depression, physical inactivity, diabetes and infrequent social contact. Recently, three more modifiable risk factors were added to the list: excessive alcohol intake and head injury in mid-life, and exposure to air pollution in later life.

“We’ve known for four or five years what the key risk factors are with Alzheimer’s disease and other forms of dementia, including the ones that are modifiable and what we can do about them,” says Hall. “The useful thing about that is that there are things we can all do. Generally, we say, what is good for our heart is good for our brains, too – being physically active, following a healthy diet, challenging your brain and having good social connections.”

Having excessive abdominal fat in middle age can be a cause of inflammation, insulin resistance and

diabetes – factors that are associated with a greater risk of dementia, says Professor Luigi Fontana, an expert in healthy ageing at the Charles Perkins Centre of the University of Sydney and author of The Path to Longevity. “It’s the apple shape that is causing inflammation,” he explains. “If you gain weight around the middle, the inflammation marker C-reactive protein (CRP) goes up, not only in your blood, but in your brain.”

The role of inflammation in neurodegenerative diseases is an area of research investigation for Dr Claire Shepherd, director of the Sydney Brain Bank at Neuroscience Research Australia (NeuRA). “There are changes in inflammation in the brain in individuals with Alzheimer’s disease but studies also suggest systemic inflammation [inflammation in the body] is associated with worsening cognitive outcomes,” she explains.

Having high cholesterol and blood pressure can also play a role, says Professor Fontana. “Some studies show improving metabolic health through nutrition and exercise, and cognitive health through brain training, can slow down decline in memory,” he says.

There’s also a good case for cutting calories. “If you restrict calories, the degeneration of the brain is much reduced,” says Professor Fontana, who conducted the initial research on intermittent fasting that gave rise to the 5:2 diet. He cites a clinical trial in the US that he was involved in where even cutting 300 calories from a daily intake of about 2,500 calories resulted in significant improvements in cholesterol levels, blood pressure, insulin sensitivity, CRP and markers of oxidative stress over a two-year period. “There’s no medication that can simultaneously ameliorate all these factors that are implicated in dementia,” says Professor Fontana.

“NUTRITION AND EXERCISE CAN SLOW DOWN DECLINE IN MEMORY.” PROFESSOR LUIGI FONTANA

“GENERALLY, WHAT IS GOOD FOR OUR HEART IS GOOD FOR OUR BRAINS, TOO.” CATHERINE HALL

The Mediterranean diet and ditching junk food are also among his recommendations. “Get rid of junk food and focus on salads, beans, nuts and wholegrains,” he says. “Just by going from processed foods and a diet high in animal products to eating more fish and vegetables, you’re already losing weight.” Portion sizes are also important. “Instead of huge plates of food, have small portions, then use the Japanese approach of ‘hara hachi bun me’ and stop eating when you’re 80 per cent full, before you’re satiated.” Eat fibre-rich food and eat slowly, he adds. “There was a study in Japan in which metabolic weight dropped just by eating slowly.”

Good-quality sleep is also a critical factor. “How you sleep is very important for the progression of dementia and Alzheimer’s disease because sleep fragmentation is causally linked with beta-amyloid and tau deposition in your brain,” says Professor Fontana. “Slow-wave sleep, is important for removing inflammation and improving the function of brain cells.”

In terms of exercise, Professor Fontana says that all types – including resistance exercise, aerobics and walking – work to improve metabolic and cognitive health. For relaxation, he says, mindfulness is beneficial, especially slow breathing. “We normally breathe about 12-16 times per minute, but a study in the journal Nature found that if you slow down to four to six breaths a minute you’re activating the parasympathetic nervous system and reducing inflammation and bringing down your heart rate and blood pressure.

“Staying socially connected with family and friends is also important as this is linked to lower levels of depression, and which can lead to inflammation and immune suppression,” says Professor Fontana. “These are not new ways, but there are well-conducted studies showing there is a real pathway through these manipulations,” he says.

RESEARCH DIRECTIONS

Researchers around the world are working to develop effective treatments for dementia, and eventually to find a cure, says Maree McCabe, CEO of Dementia Australia. “A lot of research related to finding a cure is related to Alzheimer’s disease, which is the most common form of dementia,” she explains.

“There are three main treatment options that are commonly explored for Alzheimer’s disease:

• Alzheimer’s vaccine and immunotherapy: The strategy behind the immunotherapy approach is to use the body’s own immune system to destroy beta-amyloid plaques.

• Gene therapy: An experimental technique that uses genes to treat or prevent disease. It focuses on treating diseases like Alzheimer’s disease by inserting a gene into a patient’s cells.

• Targeting beta-amyloid production: Several treatment strategies for Alzheimer’s disease rely on targeting the production of beta-amyloid or its accumulation into plaques.

“These three potential treatments are in the early stages of research and are not currently available. They are, however, all part of the research effort to find more effective treatments for Alzheimer’s disease and ultimately a cure,” says McCabe.

A research breakthrough in 2019 by scientists in New Zealand may contribute to a more effective treatment of Alzheimer’s disease. The researchers found that an inflammatory protein – tumor necrosis factor-alpha (TNFα) – becomes abnormally active in the Alzheimer’s brain, leading to impaired memory. Research has been carried out internationally using blockers of TNFα as a therapeutic for inflammatory diseases and cancer, says Professor Cliff Abraham, principal investigator with the University of Otago’s Brain Health Research Centre. “We are following up with more studies of how the TNF is signalling to nerve cells to impair the synaptic plasticity we are studying.”

Then, in mid-2020, came the announcement of a blood test that could diagnose Alzheimer’s disease with an accuracy rate of up to 96 per cent, developed by researchers at McGill University in the US together with a team in Sweden. The test is also sensitive enough to differentiate Alzheimer’s disease from other neurodegenerative disorders, including frontotemporal dementia. It will also be possible to rule out Alzheimer’s in MCI patients, indicating there is some other cause of their memory issues. “We’re not talking about in 90-yearolds, we’re talking about 60-year-olds where there’s uncertainty about the diagnosis when you’re that young,” says study co-author Dr Serge Gauthier from McGill University.

SUPPORT NETWORK

Living with dementia can be an isolating experience, but the Dementia Friends network is a global movement that is aiming to change that. Its goals are to raise public awareness of dementia, change people’s perceptions about it, and tackle stigma towards people living with dementia. A Dementia Friend is someone who wants to make a positive difference to the lives of people living with dementia through increased awareness and support.

“Some people feel uncomfortable about how to engage with someone who has dementia so that can mean they withdraw,” says Hall. “The Dementia Friends programme is about helping people to feel more comfortable. It’s a short online programme [found at alzheimers.org.nz] that takes about 20 minutes and gives a bit of insight about what people with dementia are like and tips and hints about how to go about engaging and staying connected. People can then commit to take some kind of action – get a wristband and badge or might decide to do something like have a coffee, go for a walk, volunteer somewhere. The action is important, whatever it is – something that works for the person. Two years after its launch, there are 8,000-plus Dementia Friends.”

VISIT MiNDFOOD.COM

There are 100 different forms of dementia, Alzheimer’s being one of the more common. Andrew Italia from Alzheimer’s Australia explains the signs, symptoms and strategies.