51²è¹Ý

"I can remember it like it was yesterday, in my National Health Service-supplied A-line white dress and blue cardigan, asking these older men what they knew about nutrition and what they would like to find out more about. That was the beginning of my interest in nutrition and ageing," she says.

Professor Charlton describes herself at that time as a "20-something green academic researcher", but it was this first research experience, while doing her Masters degree, that eventually led her to the stage at UOW's Big Ideas Festival in October 2019. During her 10-minute talk, Professor Charlton spoke about her research, which she hopes will help stop or slow the progression of cognitive decline and memory loss.

While we often talk about illness in ageing, Professor Charlton's passion lies in ageing well and her research helps us to understand the social- and health-related aspects of ageing.

Memory loss is generally accepted as a natural part of the ageing process; losing our keys, forgetting whether we've switched off the iron, or even forgetting somebody's name, it's normal. But as Professor Charlton points out, memory loss that causes someone to lose their way, forget common words, or be less productive at work may suggest signs of mild cognitive decline.

"By the time a person forgets their own address or telephone number, cannot manage their finances, or withdraws from social interaction, this may indicate dementia or Alzheimer's disease," says Professor Charlton, a dietitian in the School of Medicine at the 51²è¹Ý (UOW). "Dementia is not a normal part of ageing and despite efforts by scientists and clinicians to date, effective prevention and treatment remains elusive."

^{Professor Karen Charlton, from the School of Medicine, believes better health lies in purple food. Photo: Paul Jones}

It's this elusiveness that led Professor Charlton, with a background in dietetics and public health nutrition, to investigate whether diet can slow or stop the progression of cognitive decline and memory loss.

At this stage, her research is promising. Professor Charlton believes that cognitive decline can be prevented in its early stages through the foods we eat. Foods that are inexpensive, plant-based, and commonly available at the supermarket.

So which foods should you fill your trolley with? Plant-based ones that are purple, deep red, or blue. The magic of these purple foods lies in their bioactive compounds. Also known as phytonutrients, these compounds contribute to the antioxidant activity of plant-based foods.

are a group of phytonutrients that have shown potential benefits on neurocognition. Flavonoids are grouped into six subclasses, one of which is called anthocyanins. And it is the anthocyanins that give plants their purple, red and blue pigmentation that show the most promise of all flavonoids in terms of brain health. These compounds are found in fruits such as plums, blueberries, blackberries, strawberries, and cherries. They're also found in red wine, tea, coffee, and some vegetables such as red onion and red cabbage.

This is a relatively new area of research for Professor Charlton, who started looking into the potential benefits of anthocyanins about eight years ago.

"The big 'woah' moment came for me about 10 years ago when I met Professor Jim Joseph, a researcher from the USDA Human Nutrition Research Center on Ageing at Tufts University in Boston," she says.

"He told me how his research group was able to reverse memory loss in aged rats that had memory loss similar to Alzheimer's disease in humans. They were able to reverse the memory deficit in the aged rats after feeding them blueberry extract.

"I remember thinking 'This is amazing' and I started to think about how we could translate this into human studies."

At the time there weren't many human trials in this area and the research that did exist was mostly using blueberries, which posed a problem for Professor Charlton, because of the small size of the blueberry farming industry in Australia.

As fate would have it, just a short time later, Professor Charlton met a plant scientist from an Agritechnology company based in Orange, NSW. The scientist told her they had developed a way to process cherries into juice without destroying the anthocyanins - the same compound in blueberries that had shown promise in the rat studies. This was unique because normal methods for processing juice destroy many of the bioactive compounds.

It was a lightbulb moment for Professor Charlton, who then entered the complex world of neuroscience and dementia research.

"We started off with a randomised clinical trial and we were pretty ambitious. Now that I know more about the challenges of this type of research, we might not have started there," she laughs.

Professor Charlton and then PhD student Katherine Kent conducted a controlled clinical trial in older adults with Alzheimer's disease.

"We had no idea how difficult it would be to recruit people because it's a group that have a lot of difficulties, so to get them to come in and take part, it's hard. It took us 18 months to find 49 people," Professor Charlton says.

The group was randomised to get the cherry juice or to get a blackcurrant flavoured cordial over a 12-week period. During that time they took part in a range of memory assessments.

"We worked very closely with psychologists and measured all sorts of cognitive functioning, because there is no one type of test that measures memory, verbal fluency, and executive processing - it is really quite complex to measure cognitive function." The RAVLT (Rey Auditory Verbal Learning Test) was the one most sensitive to diet change.

After just six weeks Professor Charlton said they noticed a difference and by week 12 they found that people who were drinking the cherry juice daily had significantly improved scores on the memory and word recall test (RAVLT) compared to those in the control group.

"This was remarkable given the fact that our participants already had quite advanced Alzhiemer's disease. To our knowledge, this is a world first and remains the largest human trial of its kind to date," Professor Charlton said during her recent Big Ideas talk at UOW in October.

Professor Charlton and her coworkers are now working with another fruit, the Queen Garnet Plum. This Australian-bred plum was developed by Queensland government scientists and has double the levels of anthocyanins than normal plums.

While these clinical studies are in their early stages Professor Charlton is just as excited about the outcomes.

"When we provide 300ml of Queen Garnet Plum juice to healthy older people, we see a dramatic reduction in blood pressure over six hours, and this may be a clue to brain benefits over time.

Professor Charlton says anthocyanin-rich fruits have been shown to affect the brain in several ways.

"The high antioxidant content of these fruits may scavenge free-radicals and also reduce inflammation in the brain. They also have the potential to inhibit cell death of nerve cells and improve connections between the neurons, especially in the areas of the brain associated with learning and memory, the hippocampus" she says.

These studies aren't without challenges. There is a lot of complexity in food-based studies, something Professor Charlton is quick to point out when she talks about her current plum study being at the mercy of the seasons.

"There's variation in anthocyanin content of Australian grown fruit from year to year between seasons which makes it difficult to standardise the dose given in the studies. We are really trying to understand the food science of these compounds more closely because if you're going to do a clinical trial you need to be sure that the bioactive compounds in the fruit being provided are similar throughout," she says.

"There’s also a lot of variability in how individuals respond to anthocyanins. So you might eat a plum and I might eat a plum and we might metabolise it in different ways."

- Professor Karen Charlton

Gut microbiota also plays a role in this complicated process. Anthocyanins in foods are broken down quickly in the digestive tract into a range of different digestive substances called metabolites. This process is dependent on the health of an individual's gut bacteria.

Professor Charlton says they have been collecting these metabolites in blood and urine samples to better understand the mechanisms at play.

"Some of those anthocyanins are absorbed intact into your bloodstream and then they might have direct effects in two to three hours, others go through extensive metabolism where they are repackaged into more active metabolites that also may impact on brain health " she says.

"We really need to understand so many things to make sense of the research. We need to understand the fruit itself, what happens to anthocyanins when it is stored or processed, how individuals metabolise the compounds and how much is needed for benefits to the brain.. Our research has gone so much deeper now that we are trying to untangle all of the underlying mechanisms."

And for all of the complexity, it has the potential to be life-changing research. Fifty million people around the world live with dementia and this number is expected to triple over the next 30 years. According to Dementia Australia are currently living with dementia and an estimated 250 people are diagnosed each day.

"Dementia is the leading cause of disability in those over the age of 65. They, and their families, struggle to cope," Professor Charlton says.

"I mean wouldn't it be great if you've been told 'OK, you're early stage dementia, here's your medicine, but also be sure to include a variety of purple, blue and red foods', which are not only tasty, but just part of a normal, healthy lifestyle.

"Carers often ask 'What can I do to help?' and if we can tell someone to prepare a mixed berry smoothie and it's going to have a benefit, how amazing would that be? And that's what I am hoping to achieve with this work."

The fact that Professor Charlton's current research focuses heavily on fruits and vegetables isn't a surprise for someone who themselves eats a mostly vegetarian diet. However, it is in stark contrast to her childhood in Botswana, where she grew up loving meat. The irony isn't lost on Professor Charlton.

"I grew up in Botswana which is primarily a beef-producing country, that is one of its main exports. When I was a kid I loved meat, I used to have fillet steak for breakfast when I came back from boarding school, but when I was 16, I turned vegetarian," she says with a laugh.

With her current research focus and background, it's easy to assume Professor Charlton would be happy about society's obsession with "superfoods" and a more recent push for plant-based diets. It's hard to scroll through Instagram or Facebook these days without seeing an influencer promoting a vegan-inspired smoothie bowl or drinking a matcha latte.

"I think we have to be sensible in this whole debate. I think eating less meat in countries like Australia is recommended for health and planetary health reasons, but we can't all just jump on the bandwagon. Meat is a good source of protein and it's a good source of lots of micronutrients. It can be quite a polarising debate," she says.

"I don't really like the term 'superfoods' because I think it elevates individual foods to a different level. A lot of people in the social media space present themselves as nutrition experts and promote extreme diets but at the end of the day you really have to go back to the science of food. Which is why our degrees in nutrition or dietetics are primarily science based. You really need to understand the science to understand how food works."

Food science poses an interesting question here - surely once we know how anthocyanins work we can look at extracting them and turning them into a powder or pill?

"No. The same effects are not seen when the anthocyanins are taken out of the food matrix in which they naturally occur. Everybody wants to sell things as a pill. But if you look at studies that have tried to extract these compounds and provide them as a freeze-dried supplement, you just don't see the same effects," she says.

"If we can find food, regular everyday food that you put in the shopping basket, that can improve a range of conditions, I mean that's a win-win situation all round. We can't just assume 'Oh well this works in food, so let's take it out and sell it as a pill'. Magic bullets don't exist in the case of diet."

Throughout our conversation, Professor Charlton regularly mentions she's not doing this research alone. She is working with local hospital staff, psychologists, a neuroscientist, geriatricians, food scientists, and biochemists.

"It really is a whole team approach and we have very promising evidence to push forward with further research studies. Working with people from other disciplines is essential, because without their expertise, we wouldn't be able to measure the effects of these foods on brain health."

And while Professor Charlton says there's still a long way to go in terms of truly understanding how anthocyanins can help people with mild cognitive impairment or early dementia, it's where she expects exciting discoveries to be made.

"If we're going to try and intervene with diet, this is the area I think we need to be focusing on, before more damage has been done in the brain, at the early stages of the decline pathway," she says.

"We don't want to medicalise food. Food is there to be enjoyed, it's part of everyday life, but if we can identify a diet that is enjoyable and able to halt cognitive decline, then that's ultimately what we're hoping for."