Associations of BMI and Serum Urate with Developing Dementia: A Prospective Cohort Study

2020 ◽  
Vol 105 (12) ◽  
pp. e4688-e4698
Author(s):  
Zhi Cao ◽  
Chenjie Xu ◽  
Hongxi Yang ◽  
Shu Li ◽  
Fusheng Xu ◽  
...  

Abstract Context Recent studies have suggested that a higher body mass index (BMI) and serum urate levels were associated with a lower risk of developing dementia. However, these reverse relationships remain controversial, and whether serum urate and BMI confound each other is not well established. Objectives To investigate the independent associations of BMI and urate, as well as their interaction with the risk of developing dementia. Design and Settings We analyzed a cohort of 502 528 individuals derived from the UK Biobank that included people aged 37–73 years for whom BMI and urate were recorded between 2006 and 2010. Dementia was ascertained at follow-up using electronic health records. Results During a median of 8.1 years of follow-up, a total of 2138 participants developed dementia. People who were underweight had an increased risk of dementia (hazard ratio [HR] = 1.91, 95% confidence interval [CI]: 1.24–2.97) compared with people of a healthy weight. However, the risk of dementia continued to fall as weight increased, as those who were overweight and obese were 19% (HR = 0.81, 95%: 0.73–0.90) and 22% (HR = 0.78, 95% CI: 0.68–0.88) were less likely to develop dementia than people of a healthy weight. People in the highest quintile of urate were also associated with a 25% (HR = 0.75, 95% CI: 0.64–0.87) reduction in the risk of developing dementia compared with those who were in the lowest quintile. There was a significant multiplicative interaction between BMI and urate in relation to dementia (P for interaction = 0.004), and obesity strengthens the protective effect of serum urate on the risk of dementia. Conclusion Both BMI and urate are independent predictors of dementia, and there are inverse monotonic and dose-response associations of BMI and urate with dementia.

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 974.3-975
Author(s):  
T. Burkard ◽  
J. Lane ◽  
D. Holmberg ◽  
A. M. Burden ◽  
D. Furniss

Background:Dupuytren disease (DD) is multifactorial, with several genetic and environmental risk factors contributing to disease susceptibility. High body mass index, however, was suggested to be protective of DD.1 The impact of weight loss among obese patients on DD has not been assessed to date.Objectives:To assess the association between bariatric surgery and DD in a secondary care setting.Methods:We performed a propensity score (PS)-matched cohort study using data from Swedish nationwide healthcare registries (patient registry [secondary care], causes of death registry, prescribed drug registry). Patients aged 30-79 years who underwent bariatric surgery between 2006 and 2019 were matched to up to 2 obese bariatric surgery-free patients (called unexposed patients) based on their PS. PS-matching was carried out in risk set sampling to reduce selection bias, within 4 sequential cohort entry blocks to account for time trend biases. The outcome DD was defined as a diagnosis of DD in secondary care or partial or total fasciotomy of wrist or hand. After a 1-year run-in period, patients were followed in an “as-treated” approach. We applied Cox proportional hazard regression to calculate hazard ratios (HR) with 95% confidence intervals (CIs) of incident DD among bariatric surgery patients when compared to obese unexposed patients overall, and in subgroups of age, sex, bariatric surgery type, and by duration of follow-up.Results:A total of 34 959 bariatric surgery patients were PS-matched to 54 769 obese unexposed patients. A total of 71.6% of bariatric surgery patients were women. Bariatric surgery patients had a mean age of 45.5 years and a mean follow-up of 6.9 years. All patient characteristics in obese unexposed patients were highly similar. We observed 126 and 136 severe DD cases among bariatric surgery and obese unexposed patients, respectively. The risk of DD was significantly increased in bariatric surgery patients compared to obese unexposed patients (HR = 1.30, 95% CI 1.02-1.65). The risk of DD was higher in women (HR = 1.36, 95% CI 1.00-1.84) than in men (HR = 1.05, 95% CI 0.70-1.58). Age did not modify the risk of DD among bariatric surgery patients compared to obese unexposed patients. Malabsorptive bariatric surgery yielded an increased risk of DD when compared to obese unexposed patients (HR = 1.33, 95% CI 1.04-1.71), while restrictive bariatric surgery yielded a null result. The risk of DD increased with duration of follow-up (>5 years of follow-up: HR = 1.63, 95% CI 1.14-2.34, null result in earlier follow-up).Conclusion:Our results suggest that substantial weight loss is associated with a latent increased risk of severe DD in an obese population. This observation further strengthens current evidence that high body mass index is protective against DD. The latency of risk increase of DD after bariatric surgery may suggest that slowly adapting metabolic changes may be part of the mechanism of DD emergence.References:[1]Hacquebord JH, Chiu VY, Harness NG. The Risk of Dupuytren Surgery in Obese Individuals. J Hand Surg Am. 2017, 42: 149–55.Acknowledgements:We thank Prof. Dr. Jesper Lagergren (Karolinksa Institutet, Stockholm, Sweden) for hosting Dr. Theresa Burkard for a research stay at the Upper Gastrointestinal Surgery Group and making the data available for use. Furthermore, we thank Dr. Giola Santoni (Karolinksa Institutet, Stockholm, Sweden) for her technical support.Disclosure of Interests:None declared


2021 ◽  
pp. bjophthalmol-2021-319508
Author(s):  
Xianwen Shang ◽  
Zhuoting Zhu ◽  
Yu Huang ◽  
Xueli Zhang ◽  
Wei Wang ◽  
...  

AimsTo examine independent and interactive associations of ophthalmic and systemic conditions with incident dementia.MethodsOur analysis included 12 364 adults aged 55–73 years from the UK Biobank cohort. Participants were assessed between 2006 and 2010 at baseline and were followed up until the early of 2021. Incident dementia was ascertained using hospital inpatient, death records and self-reported data.ResultsOver 1 263 513 person-years of follow-up, 2304 cases of incident dementia were documented. The multivariable-adjusted HRs (95% CI) for dementia associated with age-related macular degeneration (AMD), cataract, diabetes-related eye disease (DRED) and glaucoma at baseline were 1.26 (1.05 to 1.52), 1.11 (1.00 to 1.24), 1.61 (1.30 to 2.00) and (1.07 (0.92 to 1.25), respectively. Diabetes, heart disease, stroke and depression at baseline were all associated with an increased risk of dementia. Of the combination of AMD and a systemic condition, AMD-diabetes was associated with the highest risk for incident dementia (HR (95% CI): 2.73 (1.79 to 4.17)). Individuals with cataract and a systemic condition were 1.19–2.29 times more likely to develop dementia compared with those without cataract and systemic conditions. The corresponding number for DRED and a systemic condition was 1.50–3.24. Diabetes, hypertension, heart disease, depression and stroke newly identified during follow-up mediated the association between cataract and incident dementia as well as the association between DRED and incident dementia.ConclusionsAMD, cataract and DRED but not glaucoma are associated with an increased risk of dementia. Individuals with both ophthalmic and systemic conditions are at higher risk of dementia compared with those with an ophthalmic or systemic condition only.


Author(s):  
Jakob Tarp ◽  
Anders Grøntved ◽  
Miguel A. Sanchez‐Lastra ◽  
Knut Eirik Dalene ◽  
Ding Ding ◽  
...  

Background Cardiorespiratory fitness may moderate the association between obesity and all‐cause mortality (ie, the “fat‐but‐fit” hypothesis), but unaddressed sources of bias are a concern. Methods and Results Cardiorespiratory fitness was estimated as watts per kilogram from a submaximal bicycle test in 77 169 men and women from the UK Biobank cohort and combined with World Health Organization standard body mass index categories, yielding 9 unique fitness‐fatness combinations. We also formed fitness‐fatness combinations based on bioimpedance as a direct measure of body composition. All‐cause mortality was ascertained from death registries. Multivariable‐adjusted Cox regression models were used to estimate hazard ratios and 95% CIs. We examined the association between fitness‐fatness combinations and all‐cause mortality in models with progressively more conservative approaches for accounting for reverse causation, misclassification of body composition, and confounding. Over a median follow‐up of 7.7 years, 1731 participants died. In our base model, unfit men and women had higher risk of premature mortality irrespective of levels of adiposity, compared with the normal weight–fit reference. This pattern was attenuated but maintained with more conservative approaches in men, but not in women. In analysis stratified by sex and excluding individuals with prevalent major chronic disease and short follow‐up and using direct measures of body composition, mortality risk was 1.78 (95% CI, 1.17–2.71) times higher in unfit‐obese men but not higher in obese‐fit men (0.94 [95% CI, 0.60–1.48]). In contrast, there was no increased risk in obese‐unfit women (1.09 [95% CI, 0.44–1.05]) as compared with the reference. Conclusions Cardiorespiratory fitness modified the association between obesity and mortality in men, but this pattern appeared susceptible to biases in women.


2021 ◽  
Vol 8 ◽  
Author(s):  
Sucharitha Chadalavada ◽  
Magnus T. Jensen ◽  
Nay Aung ◽  
Jackie Cooper ◽  
Karim Lekadir ◽  
...  

Aims: To investigate the effect of diabetes on mortality and incident heart failure (HF) according to sex, in the low risk population of UK Biobank. To evaluate potential contributing factors for any differences seen in HF end-point.Methods: The entire UK Biobank study population were included. Participants that withdrew consent or were diagnosed with diabetes after enrolment were excluded from the study. Univariate and multivariate cox regression models were used to assess endpoints of mortality and incident HF, with median follow-up periods of 9 years and 8 years respectively.Results: A total of 493,167 participants were included, hereof 22,685 with diabetes (4.6%). Two thousand four hundred fifty four died and 1,223 were diagnosed or admitted with HF during the follow up periods of 9 and 8 years respectively. Overall, the mortality and HF risk were almost doubled in those with diabetes compared to those without diabetes (hazard ratio (HR) of 1.9 for both mortality and heart failure) in the UK Biobank population. Women with diabetes (both types) experience a 22% increased risk of HF compared to men (HR of 2.2 (95% CI: 1.9–2.5) vs. 1.8 (1.7–2.0) respectively). Women with type 1 diabetes (T1DM) were associated with 88% increased risk of HF compared to men (HR 4.7 (3.6–6.2) vs. 2.5 (2.0–3.0) respectively), while the risk of HF for type 2 diabetes (T2DM) was 17% higher in women compared to men (2.0 (1.7–2.3) vs. 1.7 (1.6–1.9) respectively). The increased risk of HF in women was independent of confounding factors. The findings were similar in a model with all-cause mortality as a competing risk. This interaction between sex, diabetes and outcome of HF is much more prominent for T1DM (p = 0.0001) than T2DM (p = 0.1).Conclusion: Women with diabetes, particularly those with T1DM, experience a greater increase in risk of heart failure compared to men with diabetes, which cannot be explained by the increased prevalence of cardiac risk factors in this cohort.


PLoS Medicine ◽  
2021 ◽  
Vol 18 (11) ◽  
pp. e1003830
Author(s):  
Yuan Zhang ◽  
Hongxi Yang ◽  
Shu Li ◽  
Wei-dong Li ◽  
Yaogang Wang

Background Previous studies have revealed the involvement of coffee and tea in the development of stroke and dementia. However, little is known about the association between the combination of coffee and tea and the risk of stroke, dementia, and poststroke dementia. Therefore, we aimed to investigate the associations of coffee and tea separately and in combination with the risk of developing stroke and dementia. Methods and findings This prospective cohort study included 365,682 participants (50 to 74 years old) from the UK Biobank. Participants joined the study from 2006 to 2010 and were followed up until 2020. We used Cox proportional hazards models to estimate the associations between coffee/tea consumption and incident stroke and dementia, adjusting for sex, age, ethnicity, qualification, income, body mass index (BMI), physical activity, alcohol status, smoking status, diet pattern, consumption of sugar-sweetened beverages, high-density lipoprotein (HDL), low-density lipoprotein (LDL), history of cancer, history of diabetes, history of cardiovascular arterial disease (CAD), and hypertension. Coffee and tea consumption was assessed at baseline. During a median follow-up of 11.4 years for new onset disease, 5,079 participants developed dementia, and 10,053 participants developed stroke. The associations of coffee and tea with stroke and dementia were nonlinear (P for nonlinear <0.01), and coffee intake of 2 to 3 cups/d or tea intake of 3 to 5 cups/d or their combination intake of 4 to 6 cups/d were linked with the lowest hazard ratio (HR) of incident stroke and dementia. Compared with those who did not drink tea and coffee, drinking 2 to 3 cups of coffee and 2 to 3 cups of tea per day was associated with a 32% (HR 0.68, 95% CI, 0.59 to 0.79; P < 0.001) lower risk of stroke and a 28% (HR, 0.72, 95% CI, 0.59 to 0.89; P = 0.002) lower risk of dementia. Moreover, the combination of coffee and tea consumption was associated with lower risk of ischemic stroke and vascular dementia. Additionally, the combination of tea and coffee was associated with a lower risk of poststroke dementia, with the lowest risk of incident poststroke dementia at a daily consumption level of 3 to 6 cups of coffee and tea (HR, 0.52, 95% CI, 0.32 to 0.83; P = 0.007). The main limitations were that coffee and tea intake was self-reported at baseline and may not reflect long-term consumption patterns, unmeasured confounders in observational studies may result in biased effect estimates, and UK Biobank participants are not representative of the whole United Kingdom population. Conclusions We found that drinking coffee and tea separately or in combination were associated with lower risk of stroke and dementia. Intake of coffee alone or in combination with tea was associated with lower risk of poststroke dementia.


SLEEP ◽  
2022 ◽  
Author(s):  
Zheran Liu ◽  
Yaxin Luo ◽  
Yonglin Su ◽  
Zhigong Wei ◽  
Ruidan Li ◽  
...  

Abstract Study Objectives Sleep and circadian phenotypes are associated with several diseases. The present study aimed to investigate whether sleep and circadian phenotypes were causally linked with coronavirus disease 2019 (COVID-19)-related outcomes. Methods Habitual sleep duration, insomnia, excessive daytime sleepiness, daytime napping, and chronotype were selected as exposures. Key outcomes included positivity and hospitalization for COVID-19. In the observation cohort study, multivariable risk ratios (RRs) and their 95% confidence intervals (CIs) were calculated. Two-sample Mendelian randomization (MR) analyses were conducted to estimate the causal effects of the significant findings in the observation analyses. Beta values and the corresponding 95% CIs were calculated and compared using the inverse variance weighting, weighted median, and MR-Egger methods. Results In the UK Biobank cohort study, both often excessive daytime sleepiness and sometimes daytime napping were associated with hospitalized COVID-19 (excessive daytime sleepiness [often vs. never]: RR=1.24, 95% CI=1.02-1.5; daytime napping [sometimes vs. never]: RR=1.12, 95% CI=1.02-1.22). In addition, sometimes daytime napping was also associated with an increased risk of COVID-19 susceptibility (sometimes vs. never: RR= 1.04, 95% CI=1.01-1.28). In the MR analyses, excessive daytime sleepiness was found to increase the risk of hospitalized COVID-19 (MR IVW method: OR = 4.53, 95% CI = 1.04-19.82), whereas little evidence supported a causal link between daytime napping and COVID-19 outcomes. Conclusions Observational and genetic evidence supports a potential causal link between excessive daytime sleepiness and an increased risk of COVID-19 hospitalization, suggesting that interventions targeting excessive daytime sleepiness symptoms might decrease severe COVID-19 rate.


2020 ◽  
Author(s):  
Seyedeh M. Zekavat ◽  
Michael Honigberg ◽  
James Pirruccello ◽  
Puja Kohli ◽  
Elizabeth W. Karlson ◽  
...  

AbstractObjectivesTo determine whether elevated blood pressure influences risk for respiratory infection.DesignProspective, population-based epidemiological and Mendelian randomisation studies.SettingUK Biobank.Participants377,143 self-identified British descent (54% women; median age 58 years) participants in the UK Biobank.Main outcome measuresFirst incident pneumonia over an average of 8 follow-up years.Results107,310 (30%) participants had hypertension at UK Biobank enrolment, and 9,969 (3%) developed a pneumonia during follow-up. Prevalent hypertension at baseline was significantly associated with increased risk for incident respiratory disease including pneumonia (hazard ratio 1.36 (95% confidence interval 1.29 to 1.43), P<0.001), acute respiratory distress syndrome or respiratory failure (1.43 (1.29 to 1.59), P<0.001), and chronic lower respiratory disease (1.30 (1.25 to 1.36), P<0.001), independent of age, age2, sex, smoking status, BMI, prevalent diabetes mellitus, prevalent coronary artery disease, and principal components of ancestry. Mendelian randomisation analyses indicated that genetic predisposition to a 5 mmHg increase in blood pressure was associated with increased risk of incident pneumonia for SBP (1.08, (1.04 to 1.13), P<0.001) and DBP (1.11 (1.03 to 1.20), P=0.005). Additionally, consistent with epidemiologic associations, increase in blood pressure genetic risk was significantly associated with reduced forced expiratory volume in the first second, forced vital capacity, and the ratio of the two (P<0.001 for all).ConclusionsThese results strongly suggest that elevated blood pressure independently increases risk for pneumonia and reduces pulmonary function. Maintaining adequate blood pressure control, in addition to other measures, may reduce risk for pneumonia. Whether the present findings are generalizable to novel coronavirus disease 2019 (COVID-19) require further study.Summary BoxSection 1: What is already known on this topicHypertension has been associated with pneumonia in small observational studies.Based on early epidemiologic analyses, hypertension is described as a risk factor for SARS-CoV-2 infection and associated novel coronavirus disease 2019 (COVID-19).The influence of hypertension on pneumonia risk is difficult to assess in traditional observational studies.Section 2: What this study addsOur pre-COVID-19 analyses are consistent with a causal relationship between increased blood pressure and increased risk for incident respiratory infections, as well as between increased blood pressure and reduced pulmonary function.These results support hypertension as a pneumonia risk factor; efforts to optimize blood pressure may reduce risk for pneumonia.


PLoS Medicine ◽  
2022 ◽  
Vol 19 (1) ◽  
pp. e1003906
Author(s):  
Tingting Geng ◽  
Qi Lu ◽  
Zhenzhen Wan ◽  
Jingyu Guo ◽  
Liegang Liu ◽  
...  

Background Several epidemiological studies have suggested that vitamin D status is associated with risk of dementia in general populations. However, due to the synergistic effect between diabetic pathology and neuroinflammation, and the prothrombotic profile in patients with diabetes, whether vitamin D is associated with risk of dementia among patients with diabetes is unclear. This study aimed to investigate the associations of circulating vitamin D levels with risks of all-cause dementia, Alzheimer disease (AD), and vascular dementia (VD) among adults with type 2 diabetes (T2D). Methods and findings This study included 13,486 individuals (≥60 years) with T2D and free of dementia at recruitment (2006–2010) from the UK Biobank study. Serum 25-hydroxyvitamin D (25[OH]D) concentrations were measured using the chemiluminescent immunoassay method at recruitment. Serum 25(OH)D ≥ 75 nmol/L was considered sufficient, according to the Endocrine Society Clinical Practice Guidelines. Incidence of all-cause dementia, AD, and VD cases was ascertained using electronic health records (EHRs). Each participant’s person-years at risk were calculated from the date of recruitment to the date that dementia was reported, date of death, date of loss to follow-up, or 28 February 2018, whichever occurred first. Among the 13,486 individuals with T2D (mean age, 64.6 years; men, 64.3%), 38.3% had vitamin D ≥ 50 nmol/L and only 9.1% had vitamin D ≥ 75 nmol/L. During a mean follow-up of 8.5 years, we observed 283 cases of all-cause dementia, including 101 AD and 97 VD cases. Restricted cubic spline analysis demonstrated a nonlinear relationship between serum 25(OH)D and risk of all-cause dementia (Pnonlinearity < 0.001) and VD (Pnonlinearity = 0.007), and the nonlinear association reached borderline significance for AD (Pnonlinearity = 0.06), with a threshold at around a serum 25(OH)D value of 50 nmol/L for all the outcomes. Higher serum levels of 25(OH)D were significantly associated with a lower risk of all-cause dementia, AD, and VD. The multivariate hazard ratios and 95% confidence intervals for participants who had serum 25(OH)D ≥ 50 nmol/L, compared with those who were severely deficient (25[OH]D < 25 nmol/L), were 0.41 (0.29–0.60) for all-cause dementia (Ptrend < 0.001), 0.50 (0.27–0.92) for AD (Ptrend = 0.06), and 0.41 (0.22–0.77) for VD (Ptrend = 0.01). The main limitation of the current analysis was the potential underreporting of dementia cases, as the cases were identified via EHRs. Conclusions In this study, we observed that higher concentrations of serum 25(OH)D were significantly associated with a lower risk of all-cause dementia, AD, and VD among individuals with T2D. Our findings, if confirmed by replication, may have relevance for dementia prevention strategies that target improving or maintaining serum vitamin D concentrations among patients with T2D.


2020 ◽  
Vol 72 (7) ◽  
pp. 1184-1191 ◽  
Author(s):  
Vicky Tai ◽  
Ravi K. Narang ◽  
Greg Gamble ◽  
Murray Cadzow ◽  
Lisa K. Stamp ◽  
...  

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