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Healthy Lifestyle Can Slightly Lower Dementia Risk of People with High Genetic Risk

NEW YORK – A healthy lifestyle is linked to a lower risk of developing dementia, no matter a person's genetic risk, according to a new analysis, though absolute risks don't change by much.

Both lifestyle and genetic factors — such as smoking and mutations in the APOE gene — have been tied to risk of developing dementia, and a team led by researchers at the University of Exeter Medical School has now examined whether a healthy lifestyle can lower dementia risk, even among individuals with a high genetic risk of developing the condition.

In their retrospective cohort study, the researchers determined polygenic risk scores and lifestyle risk scores for nearly 200,000 individuals from the UK Biobank. They then linked those risk estimates to dementia outcomes from hospital and death records. As they reported yesterday in the Journal of the American Medical Association, they found that both polygenic risk and lifestyle risk scores were associated with increased incidence of dementia, but also that patients with high genetic risk were less likely to develop dementia if they adhered to a favorable lifestyle.

"This is the first study to analyze the extent to which you may offset your genetic risk of dementia by living a healthy lifestyle," co-author Elżbieta Kuźma, a research fellow in neuroepidemiology at the University of Exeter Medical School, said in a statement. "Our findings are exciting as they show that we can take action to try to offset our genetic risk for dementia."

To explore this question, she and her colleagues analyzed data on 196,383 participants from the UK Biobank who were at least 60 years old at baseline.

The researchers also constructed a polygenic risk score for dementia based on findings from previous genome-wide association studies. As those studies were of individuals of European ancestry, the researchers also restricted their participant cohort to the same ancestry group. They used this polygenic risk score to determine whether participants were at high, intermediate, or low genetic risk of developing dementia.

Similarly, the researchers developed a healthy lifestyle score based on four known dementia risk factors: smoking status, physical activity, diet, and alcohol consumption. They likewise used this score to determine whether participants had a favorable, intermediate, or unfavorable lifestyle for dementia risk.

The researchers then turned to hospital and death records to ascertain whether any of their cohort developed dementia over a median eight years of follow up. In all, there were 1,769 cases of all-cause dementia in that cohort.

As genetic risk of dementia increased, so did the likelihood that someone developed dementia. Of the participants with low genetic risk, 0.63 percent developed dementia, while 1.23 percent of participants with high genetic risk did. Meanwhile, 0.28 percent of participants with a favorable lifestyle developed dementia and 1.16 percent with an unfavorable lifestyle did.

When combining the two risk factors, the researchers found that, 1.78 percent of people with a high genetic risk as well as an unfavorable lifestyle developed dementia, as compared to 0.56 percent of people with a low genetic risk and favorable lifestyle.

The researchers noted, though, that there was no significant interaction between the healthy lifestyle score and the polygenic risk scores, suggesting that the association of lifestyle factors did not vary based on genetic risk. They further reported that of the participants with high genetic risk, 1.13 percent with a favorable lifestyle developed dementia, while 1.78 percent of those with an unfavorable lifestyle did, a 32 percent reduction in risk based on lifestyle.

"Some people believe it's inevitable they'll develop dementia because of their genetics," co-first author David Llewellyn from the University of Exeter Medical School and the Alan Turing Institute said in a statement. "However it appears that you may be able to substantially reduce your dementia risk by living a healthy lifestyle."