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JAMA. 2019 Jul 14. doi: 10.1001/jama.2019.9879. [Epub ahead of print]

Association of Lifestyle and Genetic Risk With Incidence of Dementia.

Author information

University of Exeter Medical School, Exeter, United Kingdom.
NIHR CLAHRC South West Peninsula (PenCLAHRC), University of Exeter Medical School, Exeter, United Kingdom.
Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Institute for Healthcare Policy and Innovation, Division of General Medicine, Institute for Social Research, University of Michigan, Ann Arbor.
Veterans Affairs Center for Clinical Management Research, Ann Arbor, Michigan.
Australian Centre for Precision Health, University of South Australia Cancer Research Institute, Adelaide, South Australia, Australia.
Population, Policy and Practice, University College London, Great Ormond Street, Institute of Child Health, London, United Kingdom.
Albertinen-Haus Centre for Geriatrics and Gerontology, Scientific Department at the University of Hamburg, Hamburg, Germany.
Department of Health Economics and Health Services Research, Hamburg Center for Health Economics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
The Alan Turing Institute, London, United Kingdom.



Genetic factors increase risk of dementia, but the extent to which this can be offset by lifestyle factors is unknown.


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.


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.


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.

[Available on 2020-01-14]

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