Association of Lifestyle and Genetic Risk With Incidence of Dementia | Dementia and Cognitive Impairment | JAMA | JAMA Network
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Original Investigation
July 14, 2019

Association of Lifestyle and Genetic Risk With Incidence of Dementia

Author Affiliations
  • 1University of Exeter Medical School, Exeter, United Kingdom
  • 2NIHR CLAHRC South West Peninsula (PenCLAHRC), University of Exeter Medical School, Exeter, United Kingdom
  • 3Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
  • 4Institute for Healthcare Policy and Innovation, Division of General Medicine, Institute for Social Research, University of Michigan, Ann Arbor
  • 5Veterans Affairs Center for Clinical Management Research, Ann Arbor, Michigan
  • 6Australian Centre for Precision Health, University of South Australia Cancer Research Institute, Adelaide, South Australia, Australia
  • 7Population, Policy and Practice, University College London, Great Ormond Street, Institute of Child Health, London, United Kingdom
  • 8Albertinen-Haus Centre for Geriatrics and Gerontology, Scientific Department at the University of Hamburg, Hamburg, Germany
  • 9Department of Health Economics and Health Services Research, Hamburg Center for Health Economics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • 10The Alan Turing Institute, London, United Kingdom
JAMA. 2019;322(5):430-437. doi:10.1001/jama.2019.9879
Key Points

Question  Is a healthy lifestyle associated with lower risk of dementia, regardless of genetic risk?

Findings  In this retrospective cohort study that included 196 383 participants of European ancestry aged at least 60 years without dementia at baseline, participants with a high genetic risk and unfavorable lifestyle score had a statistically significant hazard ratio for incident all-cause dementia of 2.83 compared with participants with a low genetic risk and favorable lifestyle score. A favorable lifestyle was associated with a lower risk of dementia and there was no significant interaction between genetic risk and healthy lifestyle.

Meaning  A healthy lifestyle was associated with lower risk of dementia among participants with low or high genetic risk.


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.