Download This Paper
Preprints with The Lancet is a collaboration between The Lancet Group of journals and SSRN to facilitate the open sharing of preprints for early engagement, community comment, and collaboration. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early-stage research papers that have not been peer-reviewed. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. The findings should not be used for clinical or public health decision-making or presented without highlighting these facts. For more information, please see the FAQs.
Association of Body Mass Index and Serum Urate with Developing Dementia: A Prospective Cohort Study of 502,528 Participants
31 Pages Posted: 11 Dec 2019
More...Abstract
Background: It has been suggested that higher body mass index (BMI) was associated with lower risk of developing dementia. However, the role of serum urate in this relationship is not well established. Serum urate is also inversely associated with dementia since a reduction of it might impair antioxidant capacity. Therefore, the purpose of this study is to investigate the associations of BMI, urate and their joint effect with developing dementia.
Methods: For this prospective cohort study, we used a cohort of 502,528 individuals derived from the UK Biobank which included people aged 37 to 73 years in whom BMI and urate were recorded between 2006 and 2010. Dementia was ascertained at follow-up using linkage to electronic health records. Cox proportional hazards models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) for the associations of BMI and urate with dementia.
Findings: During a median of 8.1 years of follow-up, a total of 2138 (0.46%) participants developed dementia. After a multivariate adjustment that included urate, people with underweight had an increased risk of dementia (HR = 1.97, 95%CI: 1.27-3.08) compared with people of healthy weight. However, the risk of dementia continued to fall as weight increased, as overweight and obesity were 23% (HR = 0.77, 95%: 0.68-0.86) and 33% (HR = 0.67, 95%CI: 0.56-0.81) less likely to develop dementia than healthy weight, respectively. People in highest quintile of urate were associated with 25% (HR = 0.75, 95% CI: 0.64-0.88) reduction of dementia than those who were in lowest quintile. Furthermore, the protective effect of the highest urate quintile on dementia was present only among people with obesity (HR = 0.67, 95% CI 0.49-0.91), there were no significant association in people of healthy weight (HR = 0.86, 95% CI 0.63-1.17). A significant interaction between BMI and urate in relation to dementia was examined (P for interaction = 0.015). These results were robust to various sensitivity analyses.
Interpretation: Overweight/obesity reduces the risk of developing dementia independently of serum urate, and there are inverse monotonic and dose-response associations of BMI and urate with incidence of dementia. Furthermore, we found that the association between BMI and dementia is moderated by urate, and overweight/obesity strengthens the protective effect of urate on dementia.
Funding Statement: This study was supported by the National Natural Science Foundation of China (91746205, 71910107004, 71673199).
Declaration of Interests: The authors declare that they have no conflicts of interests.
Ethics Approval Statement: All participants provided written informed consent and the study was approved by the NHS National Research Ethics Service (Ref: 11/NW/0382).
Keywords: BMI, obesity, serum urate, dementia
Suggested Citation: Suggested Citation