Healthy lifestyle may offset genetic risk

14th July 2019 by Prof David Llewellyn

The study was led by the University of Exeter – simultaneously published today in JAMA and presented at the Alzheimer’s Association International Conference 2019 in Los Angeles. The research found that the risk of dementia was 32 per cent lower in people with a high genetic risk if they had followed a healthy lifestyle, compared to those who had an unhealthy lifestyle.

Participants with high genetic risk and an unfavourable lifestyle were almost three times more likely to develop dementia compared to those with a low genetic risk and favourable lifestyle.

Joint lead author Dr Elżbieta Kuźma, at the University of Exeter Medical School, said: “This is the first study to analyse the extent to which you may offset your genetic risk of dementia by living a healthy lifestyle. Our findings are exciting as they show that we can take action to try to offset our genetic risk for dementia. Sticking to a healthy lifestyle was associated with a reduced risk of dementia, regardless of the genetic risk.”

The study analysed data from 196,383 adults of European ancestry aged 60 and older from UK Biobank. The researchers identified 1,769 cases of dementia over a follow-up period of eight years. The team grouped the participants into those with high, intermediate and low genetic risk for dementia.

To assess genetic risk, the researchers looked at previously published data and identified all known genetic risk factors for Alzheimer’s disease. Each genetic risk factor was weighted according to the strength of its association with Alzheimer’s disease.

To assess lifestyle, researchers grouped participants into favourable, intermediate and unfavourable categories based on their self-reported diet, physical activity, smoking and alcohol consumption. The researchers considered no current smoking, regular physical activity, healthy diet and moderate alcohol consumption as healthy behaviours. The team found that living a healthy lifestyle was associated with a reduced dementia risk across all genetic risk groups.

Joint lead author Dr David Llewellyn, from the University of Exeter Medical School and the Alan Turing Institute, said: “This research delivers a really important message that undermines a fatalistic view of dementia. Some people believe it’s inevitable they’ll develop dementia because of their genetics. However it appears that you may be able to substantially reduce your dementia risk by living a healthy lifestyle.”

First author Dr Ilianna Lourida, from the University of Exeter Medical School, said: “We know from previous research that healthy behaviors are associated with reduced risk of developing dementia. However, this is the first study that tries to disentangle the interplay between genetic risk and lifestyle. Our findings carry an empowering message: healthy lifestyle with regular physical activity, healthy diet, moderate alcohol consumption and no smoking may reduce the risk of dementia even in those with high genetic risk for developing the condition.”

Co-author Professor Elina Hypponen, from the University of South Australia, said: “This study suggests that much of dementia is preventable. There is a saying, that ‘what is good for your heart, is good for your brain’, and these results very much support that notion.”

Co-author Dr. Kenneth Langa, from the University of Michigan and Veterans Affairs Ann Arbor Healthcare System, added: “While there are of course no guarantees when predicting who will and won’t get dementia, our study adds important new evidence suggesting that your lifestyle has an impact on your brain’s health and functioning in later life, even if your genes put you at high risk.”

The study was led by the University of Exeter in collaboration with researchers from the University of Michigan, the University of Oxford, and the University of South Australia.

The work was supported in part by the National Institute on Aging of the National Institutes of Health under award P30AG024824, P30AG053760, and RF1AG055654. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. A full list of funders is provided in the paper.

The paper is entitled Association of Lifestyle and Genetic Risk With Incidence of Dementia and is published in JAMA. Authors are Lourida, I, Hannon, E., Littlejohns, T. J., Langa, K. M., Hyppönen, E., Kuźma, E., Llewellyn, D. J.

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Expert reaction:

Prof Tara Spires-Jones, UK Dementia Research Institute Programme Lead, and Deputy Director of the Centre for Discovery Brain Sciences, University of Edinburgh, said:

“This study led by Dr David Llewellyn at the University of Exeter indicates that a healthy lifestyle may offset genetic risk for developing dementia.  This is a large, well conducted study which adds to previous evidence suggesting that leading a healthy lifestyle can reduce risk of dementia.  Although authors accounted for known influences of dementia risk, this type of study cannot determine whether the self-reported healthy lifestyle was the main cause of reduced dementia risk or whether other related factors were protective.

“While this well-conducted study adds to data suggesting that a healthy lifestyle can help prevent dementia in many people, it is important to remember that some people will develop dementia no matter how healthy their lifestyle.  We need more research into the brain changes that cause the diseases underlying dementia symptoms in order to develop effective preventions and treatments for everyone affected by dementia.”

Dr Carol Routledge, Director of Research, Alzheimer’s Research UK, said:

“This well-conducted research was able to draw on the rich genetic and medical information from large numbers of volunteers held in the UK Biobank.  This crucial resource is made possible thanks to half a million volunteers and it’s allowing researchers to reveal key details about the complex, interacting factors that influence our health.

“These important findings suggest that lifestyle changes can benefit everyone regardless of a person’s genetic risk of Alzheimer’s disease.  A healthy lifestyle includes staying physically active, eating a healthy diet, drinking within recommended guidelines, and not smoking.

“This is yet more evidence that there are things we can all do to reduce our risk of developing dementia, yet research suggests that only 34% of adults think that this is possible.

“Sadly, as genetics still plays an important role in influencing the risk of Alzheimer’s, there will always be people who address many or all of these lifestyle factors and still develop the disease.  While we can’t change the genes we inherit, this research shows that changing our lifestyle can still help to stack the odds in our favour.”

Dr Fiona Carragher, Chief Policy and Research Officer, Alzheimer’s Society, said:

“From research we supported, we know that a third of dementia cases could be prevented through lifestyle changes.  This study takes our understanding a step further, showing that healthy behaviours can help even in people who have a higher risk due to their genes.

“This is a well-powered and thoughtfully designed study that starts to tease apart the complex interplay between our genes and lifestyle choices when it comes to dementia risk.  Its strengths include using a combination of known Alzheimer’s risk genes to get a more accurate indication of genetic risk and its large sample size made possible through UK Biobank.

“Dementia is the most feared condition in the over 50s.  Unsurprisingly, one of the most frequent questions we get asked is whether someone who has watched their parent develop dementia, will go on to develop it too.

“Reassuringly, this study suggests that, even if you have a high genetic risk of developing dementia, adopting risk reducing techniques like eating well, not smoking, drinking less alcohol and keeping active can significantly reduce your risk of developing dementia.  With one person developing dementia every three minutes in the UK, knowing how to lower our dementia risk couldn’t be more vital.  So hit that salad bar, swap a cocktail for a mocktail and get your exercise kit on!”

Dr John Haaga, Director of the Division of Behavioral and Social Research, U.S. National Institute on Aging, said:

“I consider that good news… No one can guarantee you’ll escape this awful disease but you can tip the odds in your favor with clean living.”