Abstract
Background
Epilepsy in Middle-aged and older adults has become a growing global health burden, with long-term alcohol consumption emerging as one of the key modifiable risk factors.
Methods
Leveraging comprehensive data from the Global Burden of Disease (GBD) 2021 study, we systematically evaluated mortality and morbidity metrics - including deaths, disability-adjusted life years (DALYs), years lived with disability (YLDs), years of life lost (YLLs), and corresponding age-standardized rates (ASRs) - across 204 countries and territories. Temporal trends from 1990 to 2021 were quantified using estimated annual percentage changes (EAPCs). For burden projections through 2050, we employed three complementary modeling approaches: Bayesian age-period-cohort (BAPC) analysis, autoregressive integrated moving average (ARIMA) modeling, and Exponential Smoothing (ES) techniques. Furthermore, we conducted decomposition analyses to differentiate the impacts of demographic shifts, population aging, and epidemiological transitions, complemented by comprehensive inequality assessments.
Results
Globally in 2021, alcohol-related epilepsy accounted for 3,003 deaths (95% uncertainty interval [UI]: 2,116-3,933) and 241,378 disability-adjusted life years (DALYs; 95% UI: 157,104–345,001) among adults aged ≥ 40 years. The disease burden demonstrated significant gender disparities, with males bearing 2.1-fold higher age-standardized DALY rates (17.09 per 100,000 population) compared to females. Geographic analysis revealed distinct patterns: middle Socio-demographic Index (SDI) quintiles showed the highest absolute case numbers, while age-standardized rates exhibited a characteristic U-shaped distribution across the SDI spectrum. Temporal trends from 1990 to 2021 showed a 67.4% increase in mortality and 64.7% rise in DALYs, contrasting with a 14.5% decline in age-standardized rates (from 19.99 to 17.09 per 100,000).
Conclusion
Alcohol-related epilepsy represents a growing and substantial public health burden among aging populations worldwide, demonstrating pronounced disparities by gender, age, and geographic region. Our findings highlight the critical need for a dual intervention approach: implementing targeted alcohol control measures while developing tailored regional strategies to address demographic shifts and epidemiological risks. These results provide compelling evidence for prioritizing alcohol regulation within public health initiatives for aging societies.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12889-025-25275-7.
Keywords: Epilepsy, Alcohol, Adults, GBD, SDI, Projections, Demography, DALYs
Introduction
Epilepsy is one of the most common neurological disorders, affecting approximately 50 million people worldwide as of 2021. With the accelerating global aging population, the incidence and prevalence of epilepsy among middle-aged and elderly individuals are rising significantly, posing a major burden on global health.Alcohol use, as a controllable independent risk factor, has garnered increasing attention in the pathogenesis of epileptic seizure.Evidence suggests that chronic alcohol consumption exacerbates neuronal hyperexcitability and disrupts inhibitory neurotransmission, particularly in elderly populations, thereby increasing the incidence of epilepsy [1, 2]. Despite advancements in understanding the neurobiological mechanisms linking alcohol misuse to seizure disorders, comprehensive analyses of the temporal burden of alcohol-attributable epilepsy in individuals aged ≥ 40 years remain sparse. This gap hinders the development of targeted preventive strategies, particularly in regions experiencing demographic aging and shifting alcohol consumption patterns [3, 4].
The interplay between long-term alcohol consumption and epilepsy is multifaceted. Acute alcohol withdrawal is a well-documented precipitant of seizures, mediated by glutamate-mediated excitotoxicity and γ-aminobutyric acid (GABA) receptor dysfunction [5]). Chronic alcohol exposure, however, may induce persistent neuroadaptations, such as hippocampal atrophy and oxidative stress, which contribute to epileptic seizure in Middle-aged and older adults [6]. Notably, aging amplifies these effects due to diminished neuroplasticity and cumulative neuronal damage, as demonstrated in rodent models of alcohol-induced neurodegeneration [7]. Epidemiological studies further indicate that alcohol-related epilepsy accounts for 10–25% of adult-onset cases, with higher prevalence in low- and middle-income countries (LMICs) where alcohol misuse is often comorbid with limited healthcare access [8, 9].
Global trends in alcohol consumption reveal a paradoxical pattern: while per capita intake has declined in high-income countries (HICs) since the 1990 s, LMICs report rising consumption rates, particularly among women and older adults [10]. This divergence underscores the need for region-specific burden assessments. For instance, a 2022 meta-analysis highlighted a 34% increase in alcohol-attributable neurological disorders in Southeast Asia between 2000 and 2019, contrasting with stable rates in Europe [11]. Such disparities may reflect differences in alcohol policies, socioeconomic determinants, and healthcare infrastructure. However, existing studies often aggregate data across broad age groups, obscuring the unique vulnerabilities of adults ≥ 40 years, who face synergistic risks from age-related metabolic decline and prolonged alcohol exposure [12].
Current literature on epilepsy burden has predominantly focused on genetic or structural etiologies, with limited emphasis on modifiable risk factors like alcohol use. For example, recent work on mitochondrial dysfunction in epilepsy explored metabolic pathways but omitted alcohol-specific analyses [13]. Similarly, pharmacological interventions targeting glutamatergic pathways, while promising, have not been evaluated in the context of alcohol-related seizure prevention [14]. This oversight is critical, as alcohol-attributable epilepsy often presents with distinct clinical features, including higher relapse rates and resistance to conventional antiepileptic drugs [15]. Furthermore, predictive models for epilepsy burden have traditionally relied on demographic aging projections without integrating dynamic risk factor trajectories, such as rising alcohol use in aging populations [16].
This study bridges these research gaps by analyzing the global burden of alcohol-associated epilepsy among individuals aged ≥ 40 years from 1990 to 2021 and projecting disease trends through 2050. Focusing on individuals aged ≥ 40 years is motivated by key neurobiological and public health considerations. The detrimental neural effects of chronic alcohol use, such as neurodegeneration, accumulate over time, making midlife the typical period for alcohol-attributable epilepsy onset [17, 18]. This age threshold helps distinguish it from forms with earlier-life origins. Furthermore, this demographic bears a significant burden of alcohol-related comorbidities, highlighting epilepsy as an under-recognized consequence and informing targeted interventions. We aim to quantify deaths, disability-adjusted life years (DALYs), Years Lived with Disability (YLDs), Years of Life Lost (YLLs), and age-standardized rates (ASRs) across 204 countries and territories and forecast future burden under current and mitigated risk scenarios. By incorporating decomposition analyses, we disentangle the contributions of population growth, aging, and epidemiological transitions, offering evidence to prioritize interventions in high-burden settings. Our findings aim to complement emerging research on metabolic risk factors in neurological disorders, such as studies on Hsp90 inhibition in neurodegenerative models [19], by highlighting actionable pathways for reducing alcohol-related epilepsy in aging populations.
Methods
To investigate the temporal trends in the burden of alcohol-associated epilepsy among adults ≥ 40 years globally from 1990 to 2021, and to predict the burden for the period 2021 to 2050, we employed a comprehensive analytical framework leveraging the Global Burden of Disease (GBD) study methodology. Alcohol consumption was defined according to the GBD 2021 Alcohol Collaborators [20]. High alcohol use was classified as any daily intake exceeding the GBD’s Theoretical Minimum Risk Exposure Level (TMREL), which minimizes population health loss and is frequently near zero.This section outlines the specific methodologies used in our study, including data sources, estimation techniques, and analysis approaches.
Data sources
All data were sourced from the GBD 2021 study [21], which is the most recent comprehensive global health assessment to date. The GBD study integrates data from various sources, including vital registration systems, household surveys, and health service utilization records, to provide estimates for over 369 diseases and injuries in 204 countries and territories. Based on the cumulative adverse effects of long-term alcohol consumption on the brain and the significant burden of alcohol-related diseases in individuals aged 40 and above, our study specifically focuses on individuals aged ≥ 40 years.
DALYs is the sum of YLLs and YLDs. It is a composite metric that combines years of life lost due to premature mortality with years lived in less-than-ideal health due to disability, providing a “gold standard” for measuring the overall burden of disease. YLLs refers to the number of healthy years of life lost due to premature death. This is calculated by comparing an individual’s actual age at death to a standard life expectancy (typically based on a standard life table). This metric places greater emphasis on deaths among younger people: the younger a person dies, the more YLLs, and the greater the contribution to the total disease burden. YLDs represents the number of years lived in a state of less-than-full health (due to illness or impairment), adjusted for the severity of the disability. It quantifies the burden arising from non-fatal health conditions. YLDs can be calculated using the formula:
 |
Here, the disability weight (DW) is a value between 0 (representing full health) and 1 (representing a health state equivalent to death), which quantifies the severity of different health conditions [22].
Statistical analysis
Firstly, we investigated the disease burden caused by epilepsy in the long-term drinking population aged over 40 globally and disaggregated by sex, age, SDI regions, GBD regions, and countries in 2021. Temporal trends from 1990 to 2021 were analyzed using linear regression to calculate estimated annual percentage changes (EAPCs) in ASRs of deaths, DALYs, YLDs, and YLLs. In accordance with GBD methodology, uncertainty propagation was rigorously conducted, with 95% uncertainty intervals carried throughout all analytical stages.
To project disease burden from 2021 to 2050, bayesian age-period-cohort (BAPC) was employed. Additionally, autoregressive integrated moving average (ARIMA) models and Exponential Smoothing (ES) models were applied for sensitivity analysis. The ARIMA model is suitable for capturing trend and seasonal components in time series. The modeling process involves: (1) testing the series for stationarity and applying differencing (I) if necessary; (2) identifying the autoregressive order (p) and moving average order (q) based on autocorrelation function and partial autocorrelation function (PACF) plots; and (3) estimating parameters using maximum likelihood method and selecting the optimal model based on Akaike Information Criterion [23, 24]. This model provides a solid statistical foundation for time series forecasting. Secondly, the ES method predicts by assigning greater weight to more recent observations, making it particularly effective in handling pronounced trend and seasonal patterns. This study primarily employs the Holt-Winters triple exponential smoothing method (which incorporates level, trend, and seasonal components) and optimizes the smoothing coefficients through grid search to minimize forecast errors. The ES model generally demonstrates high accuracy and practicality in short-term forecasting [25]. The BAPC model, on the other hand, is a specialized tool in epidemiological research that decomposes observed rates into age effects (Age), period effects (Period), and cohort effects (Cohort). The strength of the BAPC model lies in its ability not only to generate predictions but also to uncover potential underlying drivers of changes in disease burden.
To understand the contribution of different factors (e.g., population growth, aging, and epidemiological changes) to the changes in the burden of epilepsy attributable to alcohol use among adults over 40 years old, we performed decomposition analysis. Finally, health inequities were evaluated using established inequality analysis. All analyses were conducted in R (version 4.2.2).
Results
Global disease burden in 2021
In 2021, the global mortality among epilepsy patients (≥ 40 years) with long-term alcohol consumption reached 3,003 deaths (95% UI: 2,116–3,933), with an age-standardized deaths rate (ASDR) of 0.21 (95% UI: 0.15–0.28) per 100,000 population. The global DALYs reached 241,378 (95% UI: 157104–345001) cases, corresponding to an age-standardized DALYs rate (ASDAR) of 17.09 (95% UI: 11.12–24.41) per 100,000. YLDs data revealed 111,182 (95% UI: 54221–195946) cases, with an age-standardized YLDs rate (ASYLDR) of 7.86 (95% UI: 3.83–13.85) per 100,000. YLLs totaled 130,196 (95% UI: 91712–170613), with the age-standardized YLLs rate (ASYLLR) of 9.23 (95% UI: 6.5–12.1) (Supplementary Tables S1-S4).
Males exhibited higher absolute case counts than females across all metrics, and ASRs for deaths, DALYs, YLDs, and YLLs followed similar sex-specific patterns (Supplementary Figure S1, Tables S1-S4). Age-stratified analysis demonstrated a decreasing burden distribution with the aging increasing for the number of cases, which was highest in the 40–44 years old. As for the ASRs for DALYs, YLDs, and YLLs, there was no significant difference in the disease burden across age groups. For the ASDR, the disease burden increased with the age increasing, which was highest in the over 95 years old population (Supplementary Figure S2, Tables S1-S4). Geographically, middle SDI regions reported the highest absolute case numbers, and high-middle SDI regions showed the lowest number of deaths, DALYs, and YLLs cases. For the number of YLDs cases, it was the lowest in the low-middle SDI regions. The ASRs showed the “U” trend with the SDI decreasing (Figure S3, Supplementary Tables S1-S4). Substantial heterogeneity persisted across 54 BD regions and 204 countries (Figures S4-S5, Supplementary Tables S1-S4).
Temporal trend from 1990 to 2021
From 1990 to 2021, the number of cases for epilepsy attributable to alcohol use in adults over 40 years old showed an increasing trend. Specifically, the number of deaths increased from 1794 (95% UI: 1262–2338) to 3003 (95% UI: 2116–3933), the number of DALYs cases increased from 146,558 (95% UI: 96820–208425) to 241,378 (95% UI: 157104–345001), the number of YLDs cases increased from 68,363 (95% UI: 34535–116827) to 111,182 (95% UI: 54221–195946), and the number of YLLs cases increased from 78,195 (95% UI: 54998–101944) to 130,196 (95% UI: 91712–170613). However, the ASRs exhibited the decreasing trend for ASDR, ASDAR, ASYLDR, and ASYLLR. The ASDR decreased from 0.25 (95% UI: 0.17–0.32) to 0.21 (95% UI: 0.15–0.28), the ASDAR decreased from 19.99 (95% UI: 13.2–28.42.2.42) to 17.09 (95% UI: 11.12–24.41), the ASYLDR decreased from 9.33 (95% UI: 4.72–15.93) to 7.86 (95% UI: 3.83–13.85), and the ASYLLR decreased from 10.66 (95% UI: 7.5–13.9) to 9.23 (95% UI: 6.5–12.1). The EAPC of ASDR, ASDAR, ASYLDR and ASYLLR were − 0.63 (95% CI: −0.67 to −0.59), −0.68 (95% CI: −0.71 to −0.64), −0.71 (95% CI:−0.75 to −0.66) and − 0.65 (95% CI:−0.7 to −0.61) (Fig. 1, Supplementary Tables S1-S4).
Fig. 7.
Health Disparities in Alcohol-Associated Epilepsy in Adults ≥ 40 Years (1990–2021) The Results of Healthy Inequality Analysis for Epilepsy patients (≥ 40 years) with long-term alcohol consumption SII: Slope Index of Inequality; The circle represented the state, and the size of the circle represented the number
Fig. 1.
Global alcohol-related Epilepsy trends & ASRs in Adults ≥ 40 Years, 1990–2021 Absolute case counts: Increasing annual trend (bar graph) ASRs: Decreasing annual trend (dotted line)
The trends was the same as global trend foe both males and females, and the decline in ASR was greater in female than in male, with EAPC values for ASDR, ASDAR, ASYLDR, and ASYLLR being − 0.83 (95% CI: −0.91 to −0.75), −1.05 (95% CI: −1.1 to −0.99), −1.17 (95% CI: −1.27 to −1.07), and − 0.85 (95% CI: −0.93 to −0.77), respectively (Supplementary Figure S6, Tables S1-S4). As for age groups, the increasing trends for the number of cases were the same as the global trend across all age groups in adults over 40 years old from 1990 to 2021. As for the ASRs, the decreasing trends for the ASRs were the same as the global trend across younger age groups, Specifically, age showed a positive correlation with the EAPC values for each ASR, meaning that the burden decreased most significantly in the 40–44 age group, while it generally increased most substantially in the 90 + age group (Figure S7, Supplementary Tables S1-S4).
At the regional level of the SDI, the trend in number of cases for epilepsy attributable to alcohol use in adults over 40 years old in all SDI regions all showed the increasing trend. For ASRs, the ASRs showed the increasing trend in Low-middle SDI and Low SDI regions, and showed the decreasing trend in High SDI, High-middle SDI, and Middle SDI regions, The Low-middle SDI regions experienced the most substantial increase in ASR burden, with EAPC values of 1.07 (95% CI: 0.96–1.18) for ASDR, 1.07 (95% CI: 0.95 to 1.18) for ASDAR, 1.04 (95% CI: 0.92 to 1.16) for ASYLDR, and 1.08 (95% CI: 0.97 to 1.19) for ASYLLR. In contrast, the high-middle SDI regions saw the most significant reduction in ASR burden, with EAPC values of −2.21 (95% CI: −2.41 to −2.02) for ASDR, −1.91 (95% CI: −2.06 to −1.77) for ASDAR, −1.59 (95% CI: −1.7 to −1.48) for ASYLDR, and − 2.23 (95% CI: −2.43 to −2.03) for ASYLLR (Figure S8, Supplementary Tables S1-S4).
Across the various GBD regions, significant differences in the burden of epilepsy attributable to alcohol use in adults over 40 years old were observed. Hierarchical clustering analysis was performed to identify regions with similar patterns of variation in disease burden. The findings revealed that regions such as South Asia - WB, South-East Asia Region, South Asia, Limited Health System, Central Sub-Saharan Africa, World Bank Lower Middle Income, Eastern Sub-Saharan Africa, Northern Africa, Eastern Mediterranean Region, Commonwealth Low Income, Middle East & North Africa - WB, and Southeast Asia exhibited a significant increase in ASRs. Conversely, regions including African Region, Africa, World Bank Low Income, Western Africa, Minimal Health System, Sub-Saharan Africa - WB, North America, High-income North America, Commonwealth Middle Income, Western Sub-Saharan Africa, Central Africa, Southern Africa, Region of the Americas, America, Oceania, Tropical Latin America, Central Europe, and Southern Sub-Saharan Africa showed the significant decrease in absolute number (Fig. 2, Supplementary Tables S1-S4).
Fig. 2.
Cluster analysis of EAPCs in alcohol-related Epilepsy in Adults ≥ 40 Years, 1990–2021 EAPCs: estimated annual percentage changes Cluster Analysis Based on Estimated Annual Percentage Changes in Age-Standardized Rates of Alcohol-Related Epilepsy Among Older Adults (1990–2021)
Across 204 countries, the changing trend was also variable (Figure S9, Supplementary Tables S1-S4).
The predicted results from 2022 to 2050
The BAPC model predicted an downward or relatively stable trend in the number of cases and ASRs in epilepsy attributable to alcohol use in adults over 40 years old from 2022 to 2050 except for the ASYLDR for males. However, for the ARIMA model, the number of deaths, DALYs, YLDs, and YLLs was increasing for both genders. For the ASRs, the ASRs for females remained stable. For males, the ASYLDR showed the increasing trend, the ASDAR showed the decreasing trend, and the ASRs of deaths and YLLs showed the relatively stable trend. The ES model showed that the number of cases and the corresponding ASRs remained relatively stable (Figs. 3, 4 and 5). Based on the model evaluation results, we consider that the ARIMA model is likely to provide superior predictive accuracy (Supplementary, Tables S1-S6).
Fig. 3.
BAPC: Alcohol-attributable Epilepsy burden in Adults ≥ 40 Years by sex (2022–2050) BAPC: Bayesian Age-Period-Cohort Model; Shading indicates a ± 1% interval based on the 2021 rate
Fig. 4.
ARIMA: Alcohol-related Epilepsy burden in Adults ≥ 40 Years by sex (2022–2050) ARIMA: autoregressive integrated moving average Absolute case counts: bar graph(All indicators for both genders show a increasing annual trend); ASRs: dotted line
Fig. 5.
ES: Alcohol-related Epilepsy burden in Adults ≥ 40 Years by sex (2022–2050) ES(Exponential Smoothing model): case counts & ASRs stable
Decomposition analysis
Over the past 31 years, there has been a notable global increase in the number of cases in epilepsy attributable to alcohol use in adults over 40 years old. For deaths, this increase has been primarily driven by positive contributions from population, aging, and epidemiological changes, leading to a significant rise worldwide. For DALYs and YLLs, population growth and epidemiological changes remained primary drivers, they were partially mitigated by negative shifts in aging. For YLDs, the increasing were partially mitigated by negative shifts in epidemiological changes. When analyzing the trends across different SDI regions, it was observed that the increase in the number of deaths, DALYs, and YLLs cases was most prominent in low SDI regions. For the YLDs, the increase was most prominent in middle SDI regions (Fig. 6).
Figure 6.
Global trends in alcohol-related Epilepsy in Adults ≥ 40 Years: Population drivers and SDI disparities (1990–2021) Alterations in Cases of Epilepsy patients (≥ 40 years) with long-term alcohol consumption Based on Population Growth, Aging, and Epidemiological Shifts from 1990 to 2021: Global Overview and Socio-demographic Index Quintile-Specific Analysis
Health inequality analysis
Globally, the deaths and YLLs of epilepsy attributable to alcohol use in adults over 40 years old, was primarily concentrated in higher SDI areas. However, for DALYs and YLDs, was primarily concentrated in lower SDI areas (Fig. 7).
Discussion
The current study provides a comprehensive analysis of the global burden of epilepsy attributable to alcohol use in individuals aged 40 years and older. Our findings reveal several key insights into the patterns, trends, and projections of this condition, highlighting the need for tailored interventions and policies to address this significant health issue.
First, the study underscores the substantial global impact of alcohol-attributable epilepsy in this age group. In 2021, the estimated number of deaths was 3003 cases, with a corresponding ASDR of 0.21 per 100,000 population. Additionally, the global burden, measured in DALYs, reached 241,378 cases, indicating a substantial impact on health and well-being. These findings align with previous studies that have highlighted the detrimental effects of alcohol consumption on neurological health [26, 27]. The ASDAR of 17.09 per 100,000 further emphasizes the significant disease burden associated with this condition.
Sex-specific differences were also evident in our analysis, with males exhibiting higher absolute case counts across all metrics compared to females. This gender disparity is consistent with previous research indicating that males are more likely to engage in harmful drinking patterns, which may contribute to the higher burden of alcohol-related health outcomes [8, 10]. Compared to women, men exhibit higher frequencies of alcohol consumption and higher rates of alcohol abuse. Alcohol affects the excitability of neurons in the brain and causes chronic damage to the nervous system, which can induce epileptic seizures [28, 29]. Additionally, men face a higher risk of seizures during the alcohol withdrawal process. At the same time, physiological differences between men and women lead to variations in alcohol metabolism. Furthermore, men may encounter greater social pressures and are more likely to turn to alcohol as a means of stress relief. They are also more susceptible to the influence of drinking environments and cultures in daily life, leading to excessive alcohol intake. From another perspective, men tend to pay less attention to epilepsy and exhibit lower treatment compliance compared to women [30]. These factors collectively contribute to the differences in alcohol-related epilepsy burdens between the genders.The age-stratified analysis revealed that the burden was highest in the 40–44 years old age group, which suggests that this demographic may be particularly vulnerable to the neurotoxic effects of alcohol. However, for ASRs, no significant difference was observed across age groups for DALYs, YLDs, and YLLs, indicating that the burden of this condition is widespread across different age cohorts.
Geographically, our results indicate that middle SDI regions reported the highest absolute case numbers for deaths, DALYs, and YLLs, while low-middle SDI regions had the lowest number of YLDs cases. The ASRs exhibited a “U” trend with decreasing SDI, suggesting that both low and high SDI regions face significant challenges in managing this condition. These findings underscore the complex interplay between socioeconomic factors and health outcomes, and highlight the need for tailored interventions that consider regional variations in alcohol consumption patterns and healthcare resources [8, 31].
Temporal trend analysis from 1990 to 2021 revealed an increasing trend in the number of cases for epilepsy attributable to alcohol use in seniors over 40 years old. Specifically, the number of deaths, DALYs, YLDs, and YLLs cases all increased during this period. However, the ASRs for these metrics exhibited a decreasing trend, indicating that while the absolute number of cases is rising, the rate at which they occur is declining. This paradoxical finding may be due to improvements in healthcare access and quality, as well as shifts in population demographics and epidemiological factors [32, 33].
The regional trends in case numbers and ASRs were mixed, with increasing trends observed in all SDI regions for case numbers and varying trends for ASRs. This heterogeneity highlights the complex and multifaceted nature of alcohol-attributable epilepsy and underscores the need for region-specific strategies to address this condition. Hierarchical clustering analysis revealed distinct regional patterns in the burden of this condition, with some regions experiencing significant increases in ASRs while others showed decreases. These findings provide valuable insights for policymakers and healthcare providers seeking to develop targeted interventions.
The predicted results from 2022 to 2050 suggest that the number of cases and ASRs for epilepsy attributable to alcohol use in adults over 40 years old may exhibit downward or relatively stable trends, depending on the model used. The BAPC model predicts a downward or stable trend for most metrics, while the ARIMA model projects increasing trends for deaths, DALYs, YLDs, and YLLs. The ES model, on the other hand, indicates relatively stable trends for both case numbers and ASRs. These varying projections highlight the uncertainty inherent in predicting future health outcomes and underscore the importance of ongoing monitoring and evaluation to inform policy and practice [34].
Decomposition analysis provides further insights into the drivers of the increasing burden of epilepsy attributable to alcohol use. Our findings suggest that population growth, aging, and epidemiological changes have been primary drivers of the increase in deaths, DALYs, and YLLs. For YLDs, the increasing trend was partially mitigated by negative shifts in epidemiological changes. These findings underscore the need for comprehensive strategies that address the underlying factors driving this condition, including population-level interventions to reduce harmful drinking patterns and improve access to mental health and substance abuse services [35, 36].
Finally, the health inequality analysis reveals that the burden of epilepsy attributable to alcohol use is concentrated in different SDI regions depending on the metric considered. Deaths and YLLs are primarily concentrated in higher SDI areas, while DALYs and YLDs are more prevalent in lower SDI regions. These findings highlight the need for equitable access to healthcare and prevention strategies that consider the unique needs and challenges faced by different populations [37, 38].
However, a key limitation of this study lies in its reliance on data from the 2021 Global Burden of Disease (GBD 2021) report. Since then, GBD 2023 data have become gradually available and are expected to be fully released soon. Future analyses should incorporate these updated datasets to refine and validate our findings. Furthermore, given the ecological nature of GBD data, our analysis could not account for individual-level disease severity. The absence of clinical metrics means that our results may be influenced by residual confounding. Future studies utilizing detailed clinical data are needed to validate our findings by adequately controlling for disease severity. Despite these limitation, the present study represents the first research focusing on the burden of alcohol-related epilepsy among people aged 40 and above. It reveals disparities in burden across gender, age, region, and country levels in this population, providing a theoretical basis for the development of disease prevention and control strategies. The findings highlight the importance of enhancing alcohol abstinence campaigns, improving related policies, raising public health awareness, and strengthening early disease screening to mitigate the threat posed by alcohol-related epilepsy. This study underscores a significant disease burden attributable to alcohol, necessitating targeted public health strategies. Concrete policy measures should include: (1) Economic interventions, such as increasing excise taxes—a highly cost-effective measure. For instance, a 10% tax increase in the EU and UK reduced consumption by 8.5% and prevented over 3,000 fatalities. These WHO-endorsed “health taxes” curb harmful use while generating revenue for public services [39]. (2) Legislative actions to restrict alcohol advertising and availability, especially for vulnerable groups. Thailand’s 2006 advertising ban, similar to South Korea’s policies, demonstrates how such controls limit misleading promotions and protect youth, thereby improving public health. (3) Health system strengthening to enhance early detection via screening and ensure equitable access to treatment. The widespread adoption of these strategies could substantially reduce alcohol-related harms.
Conclusion
In conclusion, our study provides a comprehensive analysis of the global burden of epilepsy attributable to alcohol use in individuals aged 40 years and older. Our findings underscore the significant impact of this condition on health and well-being, as well as the need for tailored interventions and policies to address it. Future research should focus on identifying effective strategies to reduce harmful drinking patterns, improve access to healthcare services, and promote equitable health outcomes across different populations and regions.
Supplementary Information
Supplementary Material 1: Table S1. Global Trends in Alcohol-Related Epilepsy Mortality in Adults ≥ 40 Years (1990-2021).
Supplementary Material 2: Table S2. Age-Standardized DALY Rates/Numbers in Adults ≥ 40 Years Alcohol-Attributable Epilepsy (1990-2021).
Supplementary Material 3: Table S3. Age-Standardized YLD Rates/Numbers in Adults ≥ 40 Years Alcohol-Attributable Epilepsy (1990-2021).
Supplementary Material 4: Table S4. Age-Standardized YLL Rates/Numbers in Adults ≥ 40 Years Alcohol-Attributable Epilepsy (1990-2021).
Supplementary Material 5: Table S5. ARIMA and ES Model Evaluation.
Supplementary Material 6: Table S6. BAPC Model Evaluation.
Supplementary Material 7: Figure S1. Global alcohol-attributable Epilepsy burden in Adults ≥ 40 Years, by Sex (2021) Above figure(A): age-standardized rates; Below figure(B): number of cases DALYs: disability-adjusted life years; Deaths: Death toll; YLDs-disability-adjusted life years; YLLs-years of life lost Global Numbers and Age-Standardized Rates of Deaths, DALYs, YLDs, and YLLs from Epilepsy patients (≥ 40 years) with long-term alcohol consumption in 2021, Stratified by Sex Group, Males had higher absolute case counts than females in all indicators. Figure S2. Global alcohol-attributable Epilepsy burden in Adults ≥ 40 Years, by Age Group (2021) DALYs: Disability-Adjusted Life Years; For ASR (A): The Deaths increases with age (highest burden in ≥ 95 age group); No difference in other indicators For number of cases (B): All indicators show decreasing burden with age (highest in 40–44). Figure S3. Global alcohol-attributable Epilepsy burden in Adults ≥ 40 Years, by SDI (2021) SDI: Sociodemographic Index Global Numbers and Age-Standardized Rates of Deaths, DALYs, YLDs, and YLLs from Epilepsy patients (≥ 40 years) with long-term alcohol consumption in 2021, Stratified by SDI Region. Above figure(A): The ASRs showed the “U” trend with the SDI decreasing; Below figure(B): Medium SDI regions showed highest cases and burden. Figure S4. Global alcohol-attributable Epilepsy burden in Adults ≥ 40 Years, by GBD region (2021) GBD: Global Burden of Disease Above figure(A): ASRs were significantly elevated in low-income regions (World Bank/Commonwealth classifications) with limited health systems.Below figure(B): Absolute case numbers showed marked declines in these regions. Figure S5. Global alcohol-attributable Epilepsy burden in Adults ≥ 40 Years, by Country/Territory (2021) Global Numbers and Age-Standardized Rates of Deaths, DALYs, YLDs, and YLLs from Epilepsy patients (≥ 40 years) with long-term alcohol consumption in 2021, Across Countries and Territories. The color gradient represents different value ranges, increasing from red to blue, with gray indicating areas of missing data. Figure 6. Global trends in alcohol-related Epilepsy in Adults ≥ 40 Years: Population drivers and SDI disparities (1990–2021) Alterations in Cases of Epilepsy patients (≥ 40 years) with long-term alcohol consumption Based on Population Growth, Aging, and Epidemiological Shifts from 1990 to 2021: Global Overview and Socio-demographic Index Quintile-Specific Analysis. Figure S7. Global alcohol-attributable Epilepsy mortality/morbidity trends in Adults ≥ 40 Years, by Age Group (1990–2021) For number of cases (B): All indicators demonstrated age-related decreases with concurrent annual increases. Figure S8. Global alcohol-attributable Epilepsy mortality/morbidity trends in Adults ≥ 40 Years, by SDI Region (1990–2021) For ASR (A): Increasing trend in low and low-middle SDI regions; Decreasing trend in high and middle SDI regions.For number of cases (B): Increasing trend across all SDI regions. Figure S9. Global alcohol-attributable Epilepsy mortality/morbidity trends in Adults ≥ 40 Years, Across Countries/Territories (1990–2021) Global Trends in Numbers and Age-Standardized Rates of Deaths, DALYs, YLDs, and YLLs from Epilepsy patients (≥ 40 years) with long-term alcohol consumption Across Countries and Territories(1990–2021). The color scale shows variation ranges: warm tones = decrease, cool tones = increase, gray = missing data Figure legends B.
Acknowledgements
We gratefully acknowledge the Institute for Health Metrics and Evaluation (IHME) for providing the Global Burden of Disease (GBD) data.
Abbreviations
- GBD
Global Burden of disease
- DALYs
Disabilityadjusted life years
- YLDs
Years lived with disability
- YLLs
Years of life lost
- ASRs
Agestandardized rates
- ASDR
Agestandardized deaths rate
- ASYLDR
Agestandardized YLDs rate
- EAPCs
Estimated annual percentage changes
- BAPC
Bayesian AgePeriodCohort Model
- ARIMA
Autoregressive integrated moving average
- SDI
Sociodemographic Index
- GABA
Aminobutyric acid
- LMICs
Lowand middleincome countries
- HICs
Highincome countries
Authors’ contributions
All authors contributed to the study conception and design. Data curation and analysis, formal analysis and methodology were performed by DHW, MH, CG, LFS, CNL and YFL. The first draft of the manuscript was written by DHW and JHC. Conceptualization, project administration, writing—reviewing and editing, supervision and Funding acquisition by DHW and WY. And all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Funding
This work was supported by the National Natural Science Foundation of China (grant No. 8236050322).
Data availability
Data can be obtained from the following website: http://ghdx.healthdata.org/gbd-results-tool.
Declarations
Ethics approval and consent to participate
The GBD data are de-identifed and publicly available. Therefore, the study is exempted from institutional ethical board review.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Supplementary Material 1: Table S1. Global Trends in Alcohol-Related Epilepsy Mortality in Adults ≥ 40 Years (1990-2021).
Supplementary Material 2: Table S2. Age-Standardized DALY Rates/Numbers in Adults ≥ 40 Years Alcohol-Attributable Epilepsy (1990-2021).
Supplementary Material 3: Table S3. Age-Standardized YLD Rates/Numbers in Adults ≥ 40 Years Alcohol-Attributable Epilepsy (1990-2021).
Supplementary Material 4: Table S4. Age-Standardized YLL Rates/Numbers in Adults ≥ 40 Years Alcohol-Attributable Epilepsy (1990-2021).
Supplementary Material 5: Table S5. ARIMA and ES Model Evaluation.
Supplementary Material 6: Table S6. BAPC Model Evaluation.
Supplementary Material 7: Figure S1. Global alcohol-attributable Epilepsy burden in Adults ≥ 40 Years, by Sex (2021) Above figure(A): age-standardized rates; Below figure(B): number of cases DALYs: disability-adjusted life years; Deaths: Death toll; YLDs-disability-adjusted life years; YLLs-years of life lost Global Numbers and Age-Standardized Rates of Deaths, DALYs, YLDs, and YLLs from Epilepsy patients (≥ 40 years) with long-term alcohol consumption in 2021, Stratified by Sex Group, Males had higher absolute case counts than females in all indicators. Figure S2. Global alcohol-attributable Epilepsy burden in Adults ≥ 40 Years, by Age Group (2021) DALYs: Disability-Adjusted Life Years; For ASR (A): The Deaths increases with age (highest burden in ≥ 95 age group); No difference in other indicators For number of cases (B): All indicators show decreasing burden with age (highest in 40–44). Figure S3. Global alcohol-attributable Epilepsy burden in Adults ≥ 40 Years, by SDI (2021) SDI: Sociodemographic Index Global Numbers and Age-Standardized Rates of Deaths, DALYs, YLDs, and YLLs from Epilepsy patients (≥ 40 years) with long-term alcohol consumption in 2021, Stratified by SDI Region. Above figure(A): The ASRs showed the “U” trend with the SDI decreasing; Below figure(B): Medium SDI regions showed highest cases and burden. Figure S4. Global alcohol-attributable Epilepsy burden in Adults ≥ 40 Years, by GBD region (2021) GBD: Global Burden of Disease Above figure(A): ASRs were significantly elevated in low-income regions (World Bank/Commonwealth classifications) with limited health systems.Below figure(B): Absolute case numbers showed marked declines in these regions. Figure S5. Global alcohol-attributable Epilepsy burden in Adults ≥ 40 Years, by Country/Territory (2021) Global Numbers and Age-Standardized Rates of Deaths, DALYs, YLDs, and YLLs from Epilepsy patients (≥ 40 years) with long-term alcohol consumption in 2021, Across Countries and Territories. The color gradient represents different value ranges, increasing from red to blue, with gray indicating areas of missing data. Figure 6. Global trends in alcohol-related Epilepsy in Adults ≥ 40 Years: Population drivers and SDI disparities (1990–2021) Alterations in Cases of Epilepsy patients (≥ 40 years) with long-term alcohol consumption Based on Population Growth, Aging, and Epidemiological Shifts from 1990 to 2021: Global Overview and Socio-demographic Index Quintile-Specific Analysis. Figure S7. Global alcohol-attributable Epilepsy mortality/morbidity trends in Adults ≥ 40 Years, by Age Group (1990–2021) For number of cases (B): All indicators demonstrated age-related decreases with concurrent annual increases. Figure S8. Global alcohol-attributable Epilepsy mortality/morbidity trends in Adults ≥ 40 Years, by SDI Region (1990–2021) For ASR (A): Increasing trend in low and low-middle SDI regions; Decreasing trend in high and middle SDI regions.For number of cases (B): Increasing trend across all SDI regions. Figure S9. Global alcohol-attributable Epilepsy mortality/morbidity trends in Adults ≥ 40 Years, Across Countries/Territories (1990–2021) Global Trends in Numbers and Age-Standardized Rates of Deaths, DALYs, YLDs, and YLLs from Epilepsy patients (≥ 40 years) with long-term alcohol consumption Across Countries and Territories(1990–2021). The color scale shows variation ranges: warm tones = decrease, cool tones = increase, gray = missing data Figure legends B.
Data Availability Statement
Data can be obtained from the following website: http://ghdx.healthdata.org/gbd-results-tool.