Healthy Lifestyle Decreases Dementia Risk, Even With Genetic Risk

Results of a recent study are suggesting that living a healthy lifestyle could offset a person’s risk of dementia, even if that risk is genetic. 



Investigators from the University of Exeter found that risk of dementia was 32% lower in people with a genetic risk but healthy lifestyle and that patients with a high genetic risk and an unfavorable lifestyle were nearly 3 times as likely to develop dementia. 



"This research delivers a really important message that undermines a fatalistic view of dementia,” said joint lead investigator David Llewellyn, associate professor of neuroepidemiology at the University of Exeter. “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."

In order to determine whether a healthy lifestyle was associated with a Lowe risk of dementia, without regard to genetic risk, investigators carried out a retrospective cohort study on patients from the UK Biobank study. All participants were at least 60 years old and could not have cognitive impairment or dementia at baseline.

Investigators performed a polygenic risk score for dementia with low, intermediate, and high risk categories. A weighted healthy lifestyle score, that account for smoking status, physical activity, diet, and alcohol consumptions that categorized patients into favorable, intermediate, and unfavorable lifestyles was also used in the analyses.

Main outcome measure of the study was incident all-cause dementia, which investigators ascertained through hospital inpatient and death records. Investigators tested for interactions between lifestyle and polygenic risk scores, incidence rates per 1000 person-years, and analyses were stratified by genetic risk category.



A total of 502,536 participants were initially assessed and after applying inclusion criteria, a cohort of 193,383 participants were included in the analysis. The mean age of that group was 64.1 years, 52.7% were women, and median follow-up was 8.0 years. 



Upon analyses, investigators found that 61.8% of participants had a lifestyle categorized as favorable, 23.6% had an intermediate lifestyle, and 8.2% had unfavorable lifestyles. In regard to polygenic score, 20% had high risk scores, 60% had intermediate risk scores, and 20% had low risk scores.

Investigators found that 1.23% (95% CI, 1.13%-1.35%) of patients with a high genetic risk developed dementia compared with just 0.63% (95% CI, 0.56%-0.71%) of participants with low genetic risk (aHR 1.91; 95% CI, 1.64-2.23). Among participants with, both, a high genetic risk and an unfavorable lifestyle, 1.78% (95% CI, 1.38%-2.28%) developed dementia compared to 0.56% (95% CI, 0.48%-0.66%) of participants categorized as having a low genetic risk and favorable lifestyle (HR, 2.83; 95% CI, 2.09-3.83).

No significant interaction between genetic risk and lifestyle factors were identified by investigators. In the group with high genetic risk, 1.13% (95% CI, 1.01%-1.26%) with a favorable lifestyle developed dementia. Among those with an unfavorable lifestyle, 1.78% (95% CI, 1.38%-2.28%) ultimately developed dementia.

"This is the first study to analyze the extent to which you may offset your genetic risk of dementia by living a healthy lifestyle,” explained joint lead investigator Elżbieta Kuźma, a research fellow in neuroepidemiology at the University of Exeter. “Our findings are exciting as they show that we can take action to try to offset our genetic risk for dementia.”

This study, titled “Association of Lifestyle and Genetic Risk With Incidence of Dementia,” is published in JAMA and was presented at the Alzheimer's Association International Conference 2019.