Healthy lifestyle reduces genetic risk of dementia — large European analysis

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Living a healthy lifestyle may help offset a person’s genetic risk of dementia, according to research. The study was led by the University of Exeter presented at the Alzheimer’s Association International Conference 2019 in Los Angeles. The research found that the risk of dementia was 32% lower in people with a high genetic risk if they had followed a healthy lifestyle, compared to those who had an unhealthy lifestyle.

Participants with high genetic risk and an unfavourable lifestyle were almost three times more likely to develop dementia compared to those with a low genetic risk and favourable lifestyle.

Joint lead author Dr Elzbieta Kuzma, at the University of Exeter Medical School, said: “This is the first study to analyse the extent to which you may offset your genetic risk of dementia by living a healthy lifestyle. 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.”

The study analysed data from 196,383 adults of European ancestry aged 60 and older from UK Biobank. The researchers identified 1,769 cases of dementia over a follow-up period of eight years. The team grouped the participants into those with high, intermediate and low genetic risk for dementia.

To assess genetic risk, the researchers looked at previously published data and identified all known genetic risk factors for Alzheimer’s disease. Each genetic risk factor was weighted according to the strength of its association with Alzheimer’s disease.

To assess lifestyle, researchers grouped participants into favourable, intermediate and unfavourable categories based on their self-reported diet, physical activity, smoking and alcohol consumption. The researchers considered no current smoking, regular physical activity, healthy diet and moderate alcohol consumption as healthy behaviours. The team found that living a healthy lifestyle was associated with a reduced dementia risk across all genetic risk groups.

Joint lead author Dr David Llewellyn, from the University of Exeter Medical School and the Alan Turing Institute, said: “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.”

The study was led by the University of Exeter in collaboration with researchers from the University of Michigan, the University of Oxford, and the University of South Australia.

Abstract
Importance: Genetic factors increase risk of dementia, but the extent to which this can be offset by lifestyle factors is unknown.
Objective: To investigate whether a healthy lifestyle is associated with lower risk of dementia regardless of genetic risk.
Design, Setting, and Participants: A retrospective cohort study that included adults of European ancestry aged at least 60 years without cognitive impairment or dementia at baseline. Participants joined the UK Biobank study from 2006 to 2010 and were followed up until 2016 or 2017.
Exposures: A polygenic risk score for dementia with low (lowest quintile), intermediate (quintiles 2 to 4), and high (highest quintile) risk categories and a weighted healthy lifestyle score, including no current smoking, regular physical activity, healthy diet, and moderate alcohol consumption, categorized into favorable, intermediate, and unfavorable lifestyles.
Main Outcomes and Measures: Incident all-cause dementia, ascertained through hospital inpatient and death records.
Results: A total of 196 383 individuals (mean [SD] age, 64.1 [2.9] years; 52.7% were women) were followed up for 1 545 433 person-years (median [interquartile range] follow-up, 8.0 [7.4-8.6] years). Overall, 68.1% of participants followed a favorable lifestyle, 23.6% followed an intermediate lifestyle, and 8.2% followed an unfavorable lifestyle. Twenty percent had high polygenic risk scores, 60% had intermediate risk scores, and 20% had low risk scores. Of the participants with high genetic risk, 1.23% (95% CI, 1.13%-1.35%) developed dementia compared with 0.63% (95% CI, 0.56%-0.71%) of the participants with low genetic risk (adjusted hazard ratio, 1.91 [95% CI, 1.64-2.23]). Of the participants with a high genetic risk 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 (hazard ratio, 2.83 [95% CI, 2.09-3.83]). There was no significant interaction between genetic risk and lifestyle factors (P = .99). Among participants with high genetic risk, 1.13% (95% CI, 1.01%-1.26%) of those with a favorable lifestyle developed dementia compared with 1.78% (95% CI, 1.38%-2.28%) with an unfavorable lifestyle (hazard ratio, 0.68 [95% CI, 0.51-0.90]).
Conclusions and Relevance: Among older adults without cognitive impairment or dementia, both an unfavorable lifestyle and high genetic risk were significantly associated with higher dementia risk. A favorable lifestyle was associated with a lower dementia risk among participants with high genetic risk.

Authors
Ilianna Lourida, Eilis Hannon, Thomas J Littlejohns, Kenneth M Langa, Elina Hyppönen, Elzbieta Kuzma, David J Llewellyn

University of Exeter material
JAMA abstract


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