In the JournalsPerspective

Healthy lifestyle choices may counter genetic risk for dementia

A healthy lifestyle was associated with a lower risk for dementia, even among older adults with a high genetic risk, according to data simultaneously published in JAMA and presented at the Alzheimer’s Association International Conference.

“We know from previous research that both genes and lifestyle are associated with dementia risk. However, this is the first study to investigate whether healthy lifestyle may offset genetic risk for dementia,” Elżbieta Kuzma, PhD, from the University of Exeter Medical School, U.K., told Healio Psychiatry.

To examine whether a healthy lifestyle was linked to a lower risk for dementia regardless of genetic risk, researchers conducted a retrospective cohort study based on data from the U.K. Biobank study. The main outcome was incident all-case dementia among adults of European ancestry aged 60 years and older without cognitive impairment or dementia at baseline.

The investigators derived a polygenic risk score for dementia for all participants then categorized scores into low (lowest quintile), intermediate (quintiles 2 to 4), and high (highest quintile) risk. They also derived healthy lifestyle score based on four well-established dementia risk factors (no current smoking, regular physical activity, healthy diet and moderate alcohol consumption) at baseline then categorized scores into favorable, intermediate and unfavorable lifestyles.

Overall, 196,383 older adults were followed-up for a median of 8 years. Of these participants, 68.1% followed a favorable lifestyle, 23.6% had an intermediate lifestyle and 8.2% followed an unfavorable lifestyle; 20% had high polygenic risk scores, 60% had intermediate risk scores and 20% had low risk scores for dementia.

Couple holding hands 
A healthy lifestyle may offset dementia risk, according to study findings.
Source: Adobe Stock

More participants with high genetic risk developed dementia than those with low genetic risk (1.23% vs. 0.63%; adjusted HR = 1.91; 95% CI, 1.64-2.23). Of those with high genetic risk for dementia and unfavorable lifestyle, 1.78% (95% CI, 1.38-2.28) developed dementia compared with 0.56% (95% CI, 0.48-0.66) of participants with low genetic risk and favorable lifestyle (HR = 2.83; 95% CI, 2.09-3.83), according to the findings.

In addition, the researchers reported that fewer participants at high genetic risk who had favorable lifestyles developed dementia than those who had unfavorable lifestyles (1.13% vs. 1.78%; HR = 0.68; 95% CI, 0.51-0.9).

“This is a very optimistic public health message. Healthy lifestyle was associated with reduced risk of dementia regardless of genetic risk. This means that although you can't change your genes, you can try to reduce your risk of dementia by living a healthy lifestyle,” Kuzma told Healio Psychiatry. – by Savannah Demko

Disclosure: Kuzma reports grants from the James Tudor Foundation, the Mary Kinross Charitable Trust and the Halpin Trust. Please see the study for all other authors’ relevant financial disclosures.

A healthy lifestyle was associated with a lower risk for dementia, even among older adults with a high genetic risk, according to data simultaneously published in JAMA and presented at the Alzheimer’s Association International Conference.

“We know from previous research that both genes and lifestyle are associated with dementia risk. However, this is the first study to investigate whether healthy lifestyle may offset genetic risk for dementia,” Elżbieta Kuzma, PhD, from the University of Exeter Medical School, U.K., told Healio Psychiatry.

To examine whether a healthy lifestyle was linked to a lower risk for dementia regardless of genetic risk, researchers conducted a retrospective cohort study based on data from the U.K. Biobank study. The main outcome was incident all-case dementia among adults of European ancestry aged 60 years and older without cognitive impairment or dementia at baseline.

The investigators derived a polygenic risk score for dementia for all participants then categorized scores into low (lowest quintile), intermediate (quintiles 2 to 4), and high (highest quintile) risk. They also derived healthy lifestyle score based on four well-established dementia risk factors (no current smoking, regular physical activity, healthy diet and moderate alcohol consumption) at baseline then categorized scores into favorable, intermediate and unfavorable lifestyles.

Overall, 196,383 older adults were followed-up for a median of 8 years. Of these participants, 68.1% followed a favorable lifestyle, 23.6% had an intermediate lifestyle and 8.2% followed an unfavorable lifestyle; 20% had high polygenic risk scores, 60% had intermediate risk scores and 20% had low risk scores for dementia.

Couple holding hands 
A healthy lifestyle may offset dementia risk, according to study findings.
Source: Adobe Stock

More participants with high genetic risk developed dementia than those with low genetic risk (1.23% vs. 0.63%; adjusted HR = 1.91; 95% CI, 1.64-2.23). Of those with high genetic risk for dementia and unfavorable lifestyle, 1.78% (95% CI, 1.38-2.28) developed dementia compared with 0.56% (95% CI, 0.48-0.66) of participants with low genetic risk and favorable lifestyle (HR = 2.83; 95% CI, 2.09-3.83), according to the findings.

In addition, the researchers reported that fewer participants at high genetic risk who had favorable lifestyles developed dementia than those who had unfavorable lifestyles (1.13% vs. 1.78%; HR = 0.68; 95% CI, 0.51-0.9).

“This is a very optimistic public health message. Healthy lifestyle was associated with reduced risk of dementia regardless of genetic risk. This means that although you can't change your genes, you can try to reduce your risk of dementia by living a healthy lifestyle,” Kuzma told Healio Psychiatry. – by Savannah Demko

Disclosure: Kuzma reports grants from the James Tudor Foundation, the Mary Kinross Charitable Trust and the Halpin Trust. Please see the study for all other authors’ relevant financial disclosures.

    Perspective
    Christian J. Camargo

    Christian J. Camargo

    Much research in dementia often focuses on identifying genetic risk factors, as they may provide information on dementia risk, and may inform research into potential therapeutic targets. As more genetic risk factors are identified, many older adults may find themselves at higher genetic risk of dementia. It is thus reasonable for these individuals to ask, “Is there anything I can do to lower my risk?”

    The study authors have begun to address this question by studying a large cohort of individuals who at baseline were without impaired cognition or dementia, and investigated whether genetic risk and lifestyle choice affected the development of dementia of any cause. The study found that a healthy lifestyle, regardless of high or low genetic risk, was associated with a lower risk of development of dementia.

    Future studies would be required to support the causal nature of this association. If so, these findings would support the concept that older adults can lower their risk of dementia through a healthy lifestyle, regardless of their genetic risk. The implication that modifiable risk factors can decrease the risk of dementia onset has a strong potential for clinical application, and therefore warrants further study.

    • Christian J. Camargo, MD
    • Assistant professor
      Department of neurology
      University of Miami Miller School of Medicine

    Disclosures: Healio Psychiatry was unable to confirm any relevant financial disclosures at the time of publication.

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