A healthy lifestyle offsets the genetic risk of dementia

LOS ANGELES – Adherence to a healthy lifestyle reduces the risk of developing dementia, even in people with genetic risk of Alzheimer's disease (ADD), suggest new research.

Investigators found that people at high genetic risk who followed an unhealthy lifestyle were almost three times more likely to develop dementia in 8 years than those with low genetic risk and favorable lifestyle.

Fewer high-risk participants with a healthy lifestyle developed dementia than their counterparts with an unhealthy lifestyle.

This is the first study to examine in depth whether a healthy lifestyle makes up for the genetic risk of dementia, said researcher Elzbieta Kuzma, PhD, a researcher in neuroepidemiology at the Faculty of Medicine at the University of Toronto. 39, University of Exeter, England, Medscape Medical News.

"Although our study does not prove the existence of a causal link, the message to remember is very optimistic because our findings indicate that the adoption of a healthy lifestyle was associated with reduced risk of dementia, regardless of genetic risk. "

The study sends "a very important public health message," Kuzma added.

"This suggests that healthy lifestyles can help prevent or delay dementia, even in people at high genetic risk."

The findings were presented here at the International Conference of the Alzheimer's Association (AAIC) 2019. The study was also published online July 14 in the Journal of the American Medical Association.

Biobank data

The researchers used data from the British Biobank study, a cohort based on the population of more than 500,000 participants, who participated in one of the 22 UK assessment centers between 2006 and 2010.

The researchers identified in this biobank 196,383 people aged at least 60 years old (average age 64.1 years), of whom 52.7% were women, who had available genetic information and did not suffer. no dementia at first.

The researchers calculated a polygenic risk score for each subject in the study. They used previously published genome-wide association study data for AD in people of European descent, and included nearly 250,000 individual genetic variants that 39, they weighted according to the association with the MA, then normalized.

The variants included APOE but many others too, said Kuzma. "It was a truly complete polygenic risk score."

Based on this genetic information, they classified subjects into low (lower quintiles), intermediate (quintiles 2-4) and high (higher quintiles) risk of developing dementia.

The research team has also developed a healthy lifestyle index for each subject of study. They used four well-established risk factors for dementia: smoking, physical activity, diet, and alcohol consumption.

The subjects of the study self-reported this information on a questionnaire at the outset.

The researchers classified smoking as a current or non-smoking smoker. They defined regular physical activity as at least 150 minutes of moderate activity per week or 75 minutes of vigorous activity per week – or an equivalent combination.

A healthy diet relies on the consumption of at least four of the seven commonly consumed food groups that have been linked to cardiometabolic health, better end-of-life cognition and reduced risk of dementia.

"This would involve eating lots of fruits and vegetables, as well as fish and unprocessed foods," Kuzma said.

Moderate intake was defined as 0 to 14 g / day for women and 0 to 28 g / day for men.

The researchers weighted and normalized the lifestyle score. Higher scores indicate greater adherence to a healthy lifestyle.

They then ranked lifestyle outcomes into three categories: favorable lifestyles (3 or 4 healthy lifestyle factors), intermediate (2 healthy lifestyle factors) and unfavorable lifestyles (0 or 1 mode factor). of healthy life).

"Someone who does not smoke, does regular exercise, drinks alcohol in moderation and follows a healthy diet would have a favorable life score, but someone who does not does not smoke and does exercise regularly but exceeds the recommended levels for alcohol consumption and does a healthy diet would have an intermediate score, and someone who would not do any of these good things would have a unfavorable score, "said Kuzma.

Overall, 68.1% of participants followed a favorable lifestyle, 23.6% an intermediate lifestyle and 8.2% an unfavorable lifestyle. About 20% had a high polygenic risk score, 60% had an intermediate risk score, and 20% had a low risk score.

During a median 8-year follow-up period, researchers identified 1,769 cases of dementia from hospital records and combined them with data from the death registry.

The results showed that, compared to a low genetic risk, the adjusted risk ratio (HR) for the development of dementia was 1.37 (95% confidence interval). [CI]1.20 – 1.58) for intermediate genetic risk and 1.91 (95% CI, 1.64 – 2.23) for high genetic risk.

"When we included lifestyle factors in this model, the results have not changed," Kuzma said.

Compared with a favorable lifestyle, the adjusted HR to develop dementia in the intermediate group was 1.17 (95% CI, 1.01 – 1.31) and 1.35 (95% CI, 1%). , 15 to 1.58) in the unfavorable group.

"Once again, when we added genetic risk to the model, the results have not changed.This set of results tells us that lifestyle and genetic risk are independently associated with the risk of dementia", said Kuzma.

Worst combination

The researchers then looked at the combination of genetic risk and lifestyle and noted a growing risk of developing dementia, increasing genetic risk and an increasingly unhealthy lifestyle.

"The worst combination was a high genetic risk and an unfavorable lifestyle," said Kuzma.

Individuals with this combination were almost three times more likely to develop dementia than those with low genetic risk and a favorable lifestyle (HR 2.83, 95% CI 2.09 – 3.83; P <0.001).

A healthy lifestyle has reduced the risk of dementia in all genetic risk groups. Of the participants with high genetic risk, 1.13% (95% CI, 1.01% to 1.26%) developed dementia, compared to 1.78% (95% CI, 1.38%). % – 2.28%) with an unfavorable lifestyle (0.68, 95% CI, 0.51-0.90).

"Our findings consistently showed that a healthy lifestyle was associated with a reduced risk of dementia in genetic risk groups," Kuzma said. "So even people with high genetic risk can still try to reduce their risk of dementia by adopting a healthy lifestyle."

A range of mechanisms can help explain why genetic and lifestyle factors are associated with a risk of dementia. A healthy lifestyle can contribute to the risk of dementia by cardiovascular and cerebrovascular mechanisms, including a reduction in oxidative damage, antithrombotic and anti-inflammatory effects and an increase in cerebral blood flow, said the study's authors. .

Although researchers have adjusted to potential sources of known bias, unmeasured confusion and reverse causality are still possible, the authors noted. Another limitation is that lifestyle factors have been self-reported and some cases of dementia may have been overlooked.

However, research shows good agreement between identified dementia cases and primary care records. "We are pretty confident about the identified cases," said Kuzma.

Another possible limitation was that other lifestyle or environmental factors could play a role in determining the risk of dementia. And as the sample was limited to volunteers of European descent aged 60 to 73, the study might not be generalizable beyond this population.

Exciting implications

Heather M. Snyder, PhD, Senior Director of Medical and Scientific Operations, Alzheimer's Association, who chaired the conference press conference highlighting this study and other lifestyle-related studies, said that this research "continues to advance our understanding of how lifestyle and other behaviors can counteract dementia risk."

Maybe in the future, researchers will treat AD and other dementias in the same way as heart disease, Snyder said. This means, she said, "looking at the whole course of life and using behavioral interventions that could counter the factors that increase our risk throughout life".

Commenting on the study for Medscape Medical NewsMaria C. Carrillo, Ph.D., Scientific Officer, Alzheimer's Association, said this was an important step in the field.

"This has already been proven in the field of cardiovascular health: if people inherit the genes of cardiovascular disease, they can overcome it through their lifestyle.The fact that we can do it for the dementia of the disease. Alzheimer's is really exciting. "

This new information is important for patients with a close relative with dementia, she added. "The first thing they ask is:" Am I meant to get it too? – and the answer is actually no. "

The James Tudor Foundation, Mary Kinross Charitable Trust, Halpin Trust, National Institute of Health Research (NIHR) collaborated on this study. Collaborating for Leadership in Applied Health Research and Care in the Southwest Peninsula, National Council of Medical Research for Health and Research, National Institute on Aging / National Institutes of Health, and Alan Turing Institute as part of the grant from the Research Council of Engineering and Physical Sciences. Kuzma, Carrillo and Snyder did not reveal any relevant financial relationship.

International Conference of the Alzheimer's Association (AAIC) 2019: Abstract No. 31424. Presented on July 14, 2019.

JAMA. Posted online July 14, 2019. Full text

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