Genes vs. lifestyle: Study ‘undermines fatalistic view of dementia’

Aging
A new study investigates the effect of leading a healthful lifestyle on people who have a genetic predisposition to developing dementia.

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Leading a healthful lifestyle can offset the genetic risk of dementia, according to a new study.

Elżbieta Kuźma, Ph.D., and David Llewellyn, Ph.D., from the University of Exeter Medical School in the United Kingdom, are the joint lead authors of the new research, which appears in the journal JAMA.

Llewellyn, Kuźma, and colleagues also presented their findings at the Alzheimer’s Association International Conference 2019, which took place in Los Angeles, CA.

In their paper, the authors explain that while scientists know that genes and lifestyle both significantly affect Alzheimer’s risk and the likelihood of other types of dementia, they do not yet know the extent to which making healthful lifestyle choices can offset the genetic risk.

For instance, research has shown that the E4 variant of the gene that encodes the apolipoprotein E raises the risk by threefold if a person inherits one copy and up to 15 times if they have two copies of the gene.

However, a significant body of research also points to the fact that people who do not smoke, are physically active, only consume alcohol in moderation, and follow a healthful diet are at a lower risk of dementia.

So, to find out how lifestyle can influence genetic risk, Llewellyn and colleagues examined data on “196,383 participants of European ancestry aged at least 60 years” who did not have dementia at the start of the study.

Assessing lifestyle and genetic risk

The participants had enrolled in the U.K. Biobank study in 2006–2010, and researchers followed them clinically until 2016–2017.

Llewellyn and team calculated the polygenic risk score for each person. The score “captured an individual’s load of common genetic variants associated with Alzheimer’s disease and dementia risk.”

The researchers considered all of the genetic risk factors for dementia that studies have confirmed so far and calculated the risk according to how strongly these factors correlated with Alzheimer’s disease.

Then, they divided the participants into those with “low (lowest quintile), intermediate (quintiles 2 to 4), and high (highest quintile) risk” of dementia.

To assess the participants’ lifestyle, the researchers calculated a “weighted healthy lifestyle score” that included smoking status, exercise, diet, and alcohol intake. The score helped categorize participants into “favorable, intermediate, and unfavorable lifestyles.”

Genetics do not make dementia inevitable

Throughout the follow-up period, 1,769 cases of dementia occurred. Overall, the research showed that leading a healthful lifestyle correlated with a lower risk of dementia across the board, regardless of genetic risk levels.

More specifically, however, in the high genetic risk group, 1.13% of the participants with a favorable lifestyle developed dementia compared with 1.78% of those with an unfavorable lifestyle.

This translates into an “absolute risk reduction for dementia of a favorable lifestyle compared with an unfavorable lifestyle [of] 0.65%.”

“This risk reduction implies that, if lifestyle is causal, one case of dementia would be prevented for each 121 individuals per 10 years with high genetic risk who improved their lifestyle from unfavorable to favorable,” explain Llewellyn and colleagues.

“This is the first study to analyze the extent to which you may offset your genetic risk of dementia by living a healthy lifestyle,” comments co-lead author Kuźma.

“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,” she continues.

Llewellyn also comments on the empowering impact of the study findings:

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.”

David Llewellyn

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