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#Grand Rounds

Does a Healthy Lifestyle Decrease Risk of Dementia Even in Those with High Genetic Risk?

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BACKGROUND AND PURPOSE:

  • Genetics and lifestyle are both important in determining individual risk of Alzheimer’s or other forms of dementia
  • Previous studies have provided evidence that individuals with a healthy lifestyle are at a lower dementia risk
    • It is possible that a healthy lifestyle may be able to offset genetic risk of dementia
  • Lourida et al. (JAMA, 2019) examined whether a healthy lifestyle could decrease risk of dementia, even in those with a significant genetic predisposition

METHODS:

  • Retrospective cohort study
  • Participants enrolled in the UK Biobank
    • European ancestry | ≥60 years | No evidence of cognitive impairment or dementia at baseline | Genetic information available
    • Exposures based on polygenic risk score and lifestyle score  
  • Polygenic risk score for dementia: Load of common genetic variants associated with Alzheimer disease and dementia risk 
    • Low (lowest quintile)
    • Intermediate (quintiles 2 to 4)
    • High (highest quintile)
  • Healthy lifestyle score based on 4 dementia risk factors
    • Healthy behaviors score 1 point each each: No smoking | Regular physical activity | Diet (4 of 7 cardiometabolic health food groups) | Moderate alcohol consumption
    • Favorable (3 or 4 healthy factors)
    • Intermediate (2 healthy factors)
    • Unfavorable (0 or 1 healthy factors)
  • Lifestyle was ‘weighted’, adjusting for age, sex, education and socioeconomic status etc.
  • Primary outcome
    • Incident all-cause dementia

RESULTS:

  • 196,383 individuals | 1,545,433 person-years
    • Mean (SD) age: 64.1 (2.9) years
    • 52.7% were women
    • Median follow-up: 8.0 (IQR 7.4 to 8.6) years
  • Lifestyle
    • Favorable lifestyle: 68.1% | Intermediate lifestyle: 23.6% | Unfavorable lifestyle: 8.2%
  • Polygenic risk scores
    • High risk score: 20% | Intermediate risk score: 60% | Low risk score: 20%
  • Risk for developing dementia
    • High genetic risk: 1.23% (95% CI, 1.13% to 1.35%)
    • Low genetic risk: 0.63% (95% CI, 0.56% to 0.71%)
    • adjusted hazard ratio (HR): 1.91 (95% CI, 1.64 to 2.23)
  • Risk for developing dementia when taking in to account both genetic risk and lifestyle
    • High genetic risk and unfavorable lifestyle: 1.78% (95% CI, 1.38% to 2.28%)
    • Low genetic risk and favorable lifestyle: 0.56% (95% CI, 0.48% to 0.66%)
    • HR: 2.83 (95% CI, 2.09 to 3.83)
  • Risk for developing dementia in high risk group but with differing lifestyle scores
    • High genetic risk and favorable lifestyle: 1.13% (95% CI, 1.01% to 1.26%)
    • High risk and unfavorable lifestyle: 1.78% (95% CI, 1.38% to 2.28%)
    • HR: 0.68 (95% CI, 0.51 to 0.90)
  • Genetic factors and lifestyle were not related and appeared to confer independent risk (p = 0.99)

CONCLUSION:

  • A healthy lifestyle can significantly reduce risk for dementia even in those at risk due to genetic background
  • There is potential to prevent 1 case of dementia for every 121 individuals if lifestyle was improved from unfavorable to favorable
  • High genetic risk and unfavorable lifestyle was associated with a higher risk of dementia
  • Having a favorable lifestyle was associated with a lower risk of dementia even among participants with a high genetic risk

Learn More – Primary Sources:

Association of Lifestyle and Genetic Risk With Incidence of Dementia

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