Consumption of coffee and tea and risk of developing stroke, dementia, and poststroke dementia: A cohort study in the UK Biobank
Zhang Y, Yang H, Li S, Li W-d, Wang Y (2021) Consumption of coffee and tea and risk of developing stroke, dementia, and poststroke dementia: A cohort study in the UK Biobank. PLoS Med 18(11): e1003830. https://doi.org/10.1371/journal.pmed.1003830
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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.
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.
Why was this study done?
- Stroke and dementia become an increasing global health concern and bring a heavy economic and social burden worldwide.
- Considerable controversy exists on the association of coffee and tea consumption with stroke and dementia.
- Little is known about the association between the combination of tea and coffee and the risk of stroke and dementia and poststroke dementia.
What did the researchers do and find?
- This study included 365,682 participants (50 to 74 years old) from the UK Biobank who reported their coffee and tea consumption.
- We found that 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.
- Drinking 2 to 3 cups of coffee with 2 to 3 cups of tea daily were associated with a 32% lower risk of stroke and a 28% lower risk of dementia.
- Intake of coffee alone or in combination with tea was associated with lower risk of poststroke dementia.
What do these findings mean?
- These findings highlight a potential beneficial relationship between coffee and tea consumption and risk of stroke, dementia, and poststroke dementia, although causality cannot be inferred.
- These findings may be of interest to clinicians involved in the prevention and treatment of stroke, dementia, and poststroke dementia.
Dementia is characterized by a progressive and unrelenting deterioration of mental capacity that inevitably compromises independent living . Alzheimer disease and vascular dementia are the 2 main subtypes of dementia. Dementia is more of a clinical symptom than a specific disease and can be induced by cerebral degeneration, cerebrovascular diseases, traumatic brain injury, brain tumors, intracranial infection, metabolic diseases, and poisons. With the aging population trend, dementia has become an increasing global health concern and brought a heavy economic and social burden. Globally, over 50 million individuals had dementia in 2019. This number is anticipated to increase to 152 million by 2050 . Given the limited therapeutic value of drugs currently used for treating dementia, identifying the preventable risk factors of dementia is of high priority.
Stroke, accounting for 10% of all deaths globally , is a leading cause of all disability-adjusted life years . Although the age-standardized incidence and mortality of stroke have decreased globally in the past 2 decades, the absolute numbers of stroke cases and deaths have increased . Stroke and dementia confer risks for each other and share some of the same, largely modifiable, risk and protective factors. A population-based longitudinal study found that stroke and dementia shared about 60% risk and protective factors . In principle, 90% of strokes and 35% of dementia have been estimated to be preventable [7–10]. Because a stroke doubles the chance of developing dementia and stroke is more common than dementia, more than a third of dementia cases could be prevented by preventing stroke .
Coffee and tea are among the most widely consumed beverages, both in the UK and worldwide. Coffee contains caffeine and is a rich source of antioxidants and other bioactive compounds . Tea containing caffeine, catechin polyphenols, and flavonoids has been reported to play neuroprotective roles, such as antioxidative stress, anti-inflammation, inhibition of amyloid-beta aggregation, and an antiapoptotic effect . Coffee consumption is closely related to tea consumption. A prospective cohort study reported that approximately 70% of participants consumed both coffee and tea . Coffee and tea are distinct beverages with overlapping components, such as caffeine, and different biologically active constituents, including epigallocatechin gallate and chlorogenic acid . These constituents appeared to share common mechanisms—reactive oxygen species, on the other hand, different constituents also have different target molecules and therefore different biological effects . Furthermore, genetic polymorphisms in enzymes that involved in uptake, metabolism, and excretion of tea and coffee components were also associated with the differential biological activities of the 2 beverages . Additionally, studies have found the interaction between green tea and coffee on health outcomes in the Japanese population [13,16]. The Japan public health center-based study cohort reported that there was a multiplicative interaction between green tea and coffee that was associated with a lower risk of intracerebral hemorrhage . A prospective study demonstrated that there appear to be an additive interaction between green tea and coffee on mortality in Japanese patients with type 2 diabetes . Epidemiological and clinical studies have shown the benefits of coffee and tea separately in preventing dementia [17–22]. However, little is known about the association between the combination of coffee and tea and the risk of dementia. Therefore, we aimed to explore the association between the combination of coffee and tea, which could be multiplicative or additive interaction, and the risk of stroke and dementia.
Poststroke dementia refers to any dementia occurring after stroke . Poststroke dementia poses a significant public health problem, with 30% of stroke survivors suffering from dementia [23,24]. Thus, identifying and preventing the influencing factors of poststroke dementia are quite important. Epidemiological studies have found inverse associations between coffee and tea and incident stroke and dementia [25–28], but the associations between coffee and tea intake and incident poststroke dementia remain unclear. Therefore, the purpose of this study was to investigate the associations of coffee and tea separately and in combination with the risk of developing stroke, dementia, and poststroke dementia based on data from a large population-based cohort.
This study is reported as per the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline (S1 Checklist). UK Biobank has ethics approval from the North West Multi-Centre Research Ethics Committee (11/NW/0382). Appropriate informed consent was obtained from participants, and ethical approval was covered by the UK Biobank. This research has been conducted using the UK Biobank Resource under the project number of 45676. The analysis plan was drafted prospectively in February 2020 (S1 Text).
Study design and population
The UK Biobank comprises data from a population-based cohort study that recruited more than 500,000 participants (39 to 74 years old) who attended 1 of the 22 assessment centers across the UK between 2006 and 2010 . The analyses were restricted to individuals who were at least 50 years old at baseline (because most incident dementia and stroke cases occur in older adults). Participants provided extensive information via questionnaires, interviews, health records, physical measures, and blood samples. Data from individuals with self-reported prevalent stroke or dementia at baseline or a diagnosis of stroke or dementia identified in hospital records were excluded from analyses in our present study. Data from 365,682 individuals were available for analyses in our present study.
Coffee intake was assessed at baseline using a touchscreen questionnaire. Participants were asked, “How many cups of coffee do you drink each day (including decaffeinated coffee)?” Participants selected one of the following: “Less than one,” “Do not know,” “Prefer not to answer,” or specific number of cups of coffee drinking per day. If participants reported drinking more than 10 cups each day, they were asked to confirm their response. In addition, coffee drinkers were also asked “what type of coffee do you usually drink?” and were then instructed to select 1 of 6 mutually exclusive responses, as follows: “Decaffeinated coffee (any type),” “Instant coffee,” “Ground coffee (include espresso and filtered coffee), “other type of coffee,” “Do not know,” or “prefer not to answer.” We then analyzed the associations among different coffee types and the risk of incident stroke and dementia.
Tea intake was assessed at baseline using a touchscreen questionnaire. Participants were asked, “How many cups of tea do you drink each day (including black and green tea)?” Participants selected one of the following: “Less than one,” “Do not know,” “Prefer not to answer,” or specific number of cups of tea drinking per day. If participants reported drinking more than 10 cups each day, they were asked to confirm their response.
Incident stroke and dementia outcomes
Outcomes were ascertained using hospital inpatient records containing data on admissions and diagnoses obtained from the Hospital Episode Statistics for England, the Scottish Morbidity Record data for Scotland, and the Patient Episode Database for Wales. Diagnoses were recorded using the International Classification of Diseases-10th revision (ICD-10) coding system. The primary outcomes in this study were incident stroke and its 2 major component end points—ischemic stroke and hemorrhage stroke, dementia, and its 2 major component end points—Alzheimer disease and vascular dementia. Furthermore, outcomes of incident Alzheimer disease, vascular dementia, ischemic stroke, and hemorrhagic stroke were assessed separately. We defined outcomes according to the ICD-10: stroke (I60, I61, I62.9, I63, I64, I67.8, I69.0, and I69.3), ischemic stroke (I63), hemorrhagic stroke (I60 and I62.9), dementia (F00, F01, F02, F03, F05.1, G30, G31.1, and G31.8), Alzheimer disease (F00 and G30), and vascular dementia (F01).
In the present study, the selection of covariates based on (1) demographic variables, including sex, age, ethnicity background, education level, and income; and (2) a priori knowledge of potential confounding factors associated with incident stroke and dementia [30,31]. Covariates were documented including sex, age, ethnicity (White, Asian or Asian British, Black or Black British, and Other ethnic group), qualification (college or university degree, Advanced [A] levels/Advanced Subsidiary [AS] levels or equivalent, Ordinary [O] levels/General Certificate of Secondary Education [GCSE] or equivalent, Certificate of Secondary Education [CSE] or equivalent, National Vocational Qualification [NVQ] or Higher National Diploma [HND] or Higher National Certificate [HNC] or equivalent, other professional qualifications, or none of the above), income (less than £18,000, 18,000 to 30,999, 31,000 to 51,999, 52,000 to 100,000, and greater than 100,000), BMI (<25, 25 to <30, 30 to <35, and ≥35 kg/m2), smoking status (never, former, and current), alcohol status (never, former, and current), physical activity (low, moderate, and high), consumption of sugar-sweetened beverages, history of diabetes, history of coronary artery disease, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and diet pattern (healthy and unhealthy, healthy diet was based on consumption of at least 4 of 7 dietary components: (1) fruits: ≥3 servings/day; (2) vegetables: ≥3 servings/day; (3) fish: ≥2 servings/week; (4) processed meats: ≤1 serving/week; (5) unprocessed red meats: ≤1.5 servings/week; (6) whole grains: ≥3 servings/day; (7) refined grains: ≤1.5 servings/day [32–35]) (S1 Table).
Baseline characteristics of the samples were summarized across tea and coffee intake as percentages for categorical variables and means and standard deviations (SDs) for continuous variables. Baseline characteristics of the study population were compared across coffee or tea intake categories using analysis of variance (ANOVA) or Mann–Whitney U test for continuous variables and chi-squared tests for categorical variables. Restricted cubic spline models were used to evaluate the relationship between coffee, tea, and their combination and incident stroke and dementia, with 4 knots at the 25th, 50th, 75th, and 95th centiles. In the spline models, we adjusted for sex, age, ethnicity, education, income, body mass index (BMI), physical activity, alcohol status, smoking status, diet pattern, consumption of sugar-sweetened beverages, HDL, LDL, history of cancer, history of diabetes, history of CAD, and hypertension; further, we adjusted for coffee in tea analysis or tea in coffee analysis. To analyze the association between coffee and tea intake categories and new onset outcomes, we defined coffee and tea intake into the following categories: 0, 0.5 to 1, 2 to 3, and ≥4 cups/day. We used Cox proportional hazard models to estimate the associations of coffee and tea intake categories with the incidence of stroke and dementia. The proportional hazards assumptions for the Cox model were tested using Schoenfeld residuals method; no violation of the assumption was observed. The duration of follow-up was calculated as a timescale between the baseline assessment and the first event of stroke or dementia, death, loss of follow-up, or on June 31, 2020, which was the last hospital admission date. Cox regression models were adjusted for sex, age, ethnicity, qualification, income, BMI, physical activity, alcohol status, smoking status, history of cancer, history of diabetes, history of CAD, HDL, LDL, diet pattern, consumption of sugar-sweetened beverages, and hypertension, and we adjusted for coffee in tea analysis or for tea in coffee analysis. If covariate information was missing (<20%), we used multiple imputations based on 5 replications and a chained equation method in the R MI procedure to account for missing data. Detailed information on missing data was shown in S2 Table. We also used Cox regression to assess the association of coffee and tea with dementia among individuals with stroke. The P-value used for heterogeneity corresponded to the chi-squared test statistic for the likelihood ratio test comparing models with and without interaction between coffee and tea.
Several additional analyses were performed to assess the robustness of our study results. First, we used stratification analysis to examine whether the association between tea and coffee and the risk of stroke and dementia varied by age (<65 versus ≥65 years), sex, smoking status, alcohol status, physical activity, BMI, and diet pattern. The risks of incident stroke and dementia were explored in a series of sensitivity analyses by excluding participants with major prior diseases (e.g., diabetes, CAD, and cancer) at baseline and excluding events occurring during the first 2 years of follow-up. Additionally, we performed the analysis by including participants younger than 50 years old and conducted the analysis with additional more detail adjustment for smoking (never smokers, former smokers quitted >5 years ago, former smokers quitted ≤5 years, current smokers <10 cigarettes per day, current smokers 10 to 20 cigarettes per day, and current smokers 20+ cigarettes per day) and alcohol status (never drinkers, former drinkers, current drinkers <7 g per day, current drinkers 7 to 16 g per day, and current drinkers >16 g per day). Finally, we assessed the competing risk of nonstroke or nondementia death on the association between the combination of tea and coffee and the risks of stroke and dementia using the subdistribution method proposed by Fine and Grey . All P-values were 2 sided, with statistical significance set at less than 0.05. All the analyses were performed using R software, version 3.6.1, and STATA 15.
At baseline, 502, 507 participants were assessed. After excluding participants younger than 50 years old (n = 132,168), without information on tea or coffee intake (n = 2,074), with prevalent stroke or dementia (n = 2,583), 365,682 participants were ultimately included in the present study to assess associations of coffee and tea with stroke and dementia (S1A Fig). Of 502,507 participants, after excluding participants with no incidence of stroke up to June 31, 2020 (n = 488,581), without information on tea or coffee intake (n = 114), and incident dementia before stroke (n = 460), 13,352 participants were ultimately included in this study to assess the association of coffee and tea with poststroke dementia (S1B Fig).
Of the 365,682 participants, the mean age was 60.4 ± 5.1 years, and 167,060 (45.7%) were males. In total, 75,986 (20.8%) participants were noncoffee drinkers, and 50,009 (13.7%) participants were nontea drinkers. The distribution of the combination of coffee and tea intake is shown in S2 Fig. Of the 365,682 participants, 59,558 (16.29%) participants reported drinking 0.5 to 1 cup of coffee and ≥4 cups of tea per day, accounting for the largest proportion, followed by 50,015 (13.68%) participants reported drinking 0 cup of coffee and ≥4 cups of tea per day; besides, 44,868 (12.27%) participants reported drinking 2 to 3 cups of coffee and 2 to 3 of tea per day. The baseline characteristics of the participants are provided in Table 1. Compared to the characteristics of participants who did not drink coffee, coffee drinkers were more likely to be male, white, former smokers, current drinkers, have a university degree, and have a high income. Likewise, as compared to nontea drinkers, tea drinkers were more likely to be males, never smokers, and current drinkers, with a university degree, and high physical activity. Furthermore, compared to participants who drank neither coffee nor tea, those who drank both beverages were more likely to be older adults, males, white, former smokers, current drinkers, have a university degree, and have a high income (S3 Table). Coffee intake (cups/day) was related to tea intake (r = −0.337, P < 0.001). Both coffee and tea drinking were related to sex, age, ethnicity, qualification, income, BMI, physical activity, alcohol status, smoking status, consumption of sugar-sweetened beverages, LDL, cancer, diabetes, and CAD, but not related to HDL (S4 Table). During a median follow-up of 11.35 years for new onset disease, 10,053 participants (2.8%) developed stroke (5,630 ischemic strokes and 1,815 hemorrhagic strokes), and 5,079 participants (1.4%) developed dementia (2,128 Alzheimer disease and 1,223 vascular dementia).
Citation: Zhang Y, Yang H, Li S, Li W-d, Wang Y (2021) Consumption of coffee and tea and risk of developing stroke, dementia, and poststroke dementia: A cohort study in the UK Biobank. PLoS Med 18(11): e1003830. https://doi.org/10.1371/journal.pmed.1003830
Academic Editor: Joshua Z. Willey, Columbia University, UNITED STATES
Received: February 1, 2021; Accepted: September 30, 2021; Published: November 16, 2021
Copyright: © 2021 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: Data from the UK Biobank cannot be shared publicly, however, data are available from the UK Biobank Institutional Data Access / Ethics Committee (contact via http://www.ukbiobank.ac.uk/ or contact by email at [email protected]) for researchers who meet the criteria for access to confidential data.
Funding: This study was funded by the National Natural Science Foundation of China (Grant No. 91746205: http://www.nsfc.gov.cn/english/site_1/index.html), received by YW. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Abbreviations: A, Advanced; ANOVA, analysis of variance; AS, Advanced Subsidiary; BMI, body mass index; CAD, cardiovascular arterial disease; CSE, Certificate of Secondary Education; CVD, cardiovascular disease; DBP, diastolic blood pressure; GCSE, General Certificate of Secondary Education; HDL, high-density lipoprotein; HNC, Higher National Certificate; HND, Higher National Diploma; HR, hazard ratio; ICD-10, International Classification of Diseases-10th revision; LDL, low-density lipoprotein; NHS, National Health Service; NVQ, National Vocational Qualification; O, Ordinary; SBP, systolic blood pressure; SD, standard deviation; STROBE, Strengthening the Reporting of Observational Studies in Epidemiology