Abstract
Introduction
In most countries and territories, current data on the burden of Alzheimer’s disease (AD) and other dementias are lacking. We aimed to assess the trends, burden, and inequalities of AD and other dementias at global, regional, and national level from 1990 to 2021.
Methods
The data on disease burden of AD and other dementias during 1990–2021 were extracted from Global Burden of Disease and Risk Factors Study 2021 (GBD 2021). Average annual percentage changes (AAPCs) of age-standardized prevalence, mortality, and disability-adjusted life-years (DALYs) were estimated as an indicator to evaluate the healthcare system.
Result
The global age-standardized prevalence of AD and other dementias increased from 672 (95% uncertainty interval: 589 to 764) per 100,000 population in 1990 to 694 (603 to 794) per 100,000 population in 2021, with AAPCs of 0.09% (95% confidence interval: 0.06% to 0.11%). However, age-standardized mortality did not change (AAPCs: 0.00% [−0.01% to 0.02%]) and age-standardized DALYs slightly increased from 446 (206 to 958) to 451 (213 to 950) per 100,000 population (AAPCs: 0.01% [0.00% to 0.03%]). While the highest prevalence remained in population aged 65–69 and the countries with a high-middle sociodemographic index (SDI) such as East Asia (e.g., China), the highest mortality and DALYs were found in population aged 65–69 and the countries with a low-middle SDI such as South Asia (e.g., India). High fasting plasma glucose ranked the highest risk factor for DALYs during 1990–2021.
Conclusion
The global increased prevalence of AD and other dementias may partly be attributed to population aged 65–69 in the countries with a high-middle SDI (e.g., China), whereas mortality and DALY ratio of population aged 65–69 from the countries with a low-middle SDI (e.g., India) is most significantly growing. Controlling of high fasting plasma glucose may be needed for the reduction of DALYs from AD and other dementias.
Keywords: Alzheimer’s disease, Dementia, Disease burden, Prevalence, Disability-adjusted life-years
Introduction
Dementia is a significant cause of disability in people over 65 years worldwide [1]. It is a syndrome characterized by a range of symptoms, including impairments in memory, language, problem-solving, and other mental abilities [2]. Alzheimer’s disease (AD) is the most common type of dementia [3]. AD is primarily characterized by comprehensive dementia, including cognitive and memory disorders [4, 5]. Two out of every 10 individuals diagnosed with neurological disorders will have AD [6, 7]. Javaid et al. [8] showed that AD and other dementias are rising rapidly and will be more than double in mortality burden over the next 20 years. Unfortunately, there is no effective method available to prevent or cure dementia [4, 9].
The number of people with dementia is estimated to have a noticeable increase from 57.4 million in 2019 to 152.8 million in 2050 [10]. Dementia ranks the ninth cause of death in 1990, rises the seventh in 2017, and likely reaches the second by 2040 [11]. The global economic cost on dementia is predicted to be USD 2.54 trillion in 2030 and USD 9.12 trillion in 2050 [12]. Chen et al. [13] used a health-augmented macroeconomic model and predicted that AD and other dementias would cost the world economy 14,513 (95% uncertainty interval [UI]: 12,106–17,778) billion international dollars from 2020 to 2050, equivalent to 0.421% (95% UI: 0.351–0.515) of annual global GDP. Nandi A et al. [14] used country-specific extrapolations of the value of a statistical life year and its future projections and predicted that the global economic burden of AD and related dementias was USD 2.8 trillion in 2019 and the burden would increase to USD 4.7 trillion (95% UI: USD 4 trillion–5.5 trillion) in 2030, USD 8.5 trillion (USD 6.8 trillion–10.8 trillion) in 2040, and USD 16.9 trillion (USD 11.3 trillion–27.3 trillion) in 2050. Thus, monitoring the epidemiological trends and the risk factors is critical for the global prevention of AD and other dementia [6, 15].
In May 2024, the data from Global Burden of Disease and Risk Factors Study 2021 (GBD 2021) were released. To track and update the epidemiology trends of AD and other dementias, I investigated AD and other dementias-associated prevalence, mortality, and disability-adjusted life-years (DALYs) at global, regional, and national level during 1990–2021 by age, sex, and sociodemographic index (SDI). I also assessed risk factors that might have an influence on DALYs among people with AD and other dementias.
Materials and Methods
Study Population and Data Collection
To analyze the global burden of AD and other dementias, I accessed the repeated cross-sectional data from the GBD 2021 [16] of the Global Health Data Exchange (GHDx), encompassing the global burden of 371 diseases and injuries and 88 risk factors, including AD and other dementias, across 21 regions and 204 countries and territories from 1990 to 2021. The study population comprised the overall people with AD and other dementias. From the GBD 2021, I extracted information on AD and other dementias based on a global scale, sex, age, region, country-specific numbers, percentages, and rates of prevalence, mortality, and DALYs, and each risk factor for DALYs with corresponding 95% UI. DALYs were used to represent a metric method for quantifying the contribution of a specific risk factor to the burden of AD and other dementias. It informs the changes including increase, reduction, and unchanged in current burden of AD and other dementias. DALYs equal to the sum of years of life lost and years lived with disability. Years of life lost is mainly a measure on how many years have been lost to an ideal healthy life measured in years, whereas years lived with disability is obtained by using microsimulation after adjusting for comorbidity. The methodology used in the GBD 2021 is described [17–19] (also see the methods section of the online suppl. material; for all online suppl. material, see https://doi.org/10.1159/000543578).
In GBD 2021 [16], AD and other dementias were defined by the Diagnostic and Statistical Manual of Mental Disorders III, IV, or V, or ICD case definitions. To estimate nonfatal burdens and complications of AD and other dementias, a Bayesian meta-regression modeling tool named DisMod-MR 2.1 model was used to analyze 4,093 location years of data from survey microdata, the scientific literature, and insurance claims [18]. Estimates of both nonfatal and fatal outcomes in people with AD and other dementias include those attributed to complications from this disease. The GBD extrapolates and models the reported AD and other dementias-related data to develop a database applicable to most countries, with no age restrictions on the input raw data. To allow for smoothing over time, age, and location in areas without complete datasets, spatiotemporal Gaussian process regression [20] was used to model the GBD 2021 input data. Detailed information on the input data and methodology for AD and other dementias was provided in the methods section of the online supplementary materials.
For each country, I calculated its SDI (ranges from 0 to 1), a composite indicator of the social and economic conditions. Here, 0 represented the lowest education level, lowest per capita income, and highest fertility rate, whereas 1 represented the highest education level, highest per capita income, and lowest fertility rate. Based on SDI value, 204 countries and regions are divided into five categories: low, low-middle, middle, high-middle, and high. Based on AD and other dementias, population age is divided into 12 subgroups including 40–44 years, 45–49 years, 50–54 years, 55–59 years, 60–64 years, 65–69 years, 70–74 years, 75–79 years, 80–84 years, 85–89 years, 90–94 years, and ≥95 years. I extracted data on AD and other dementias, based on a global scale, two sexes including men and women, five SDI levels, 12 age subgroups, 21 subregions of geographically proximate countries that have similar epidemiological profiles, and 204 countries and territories from the GBD 2021 [16].
Statistical Analysis
A descriptive analysis was conducted to explore the burden of AD and other dementias. Based on five levels including a global scale, sex, age, regions, and countries, I compared the age-standardized prevalence, mortality, and DALYs (per 100,000 population) of AD and other dementias. These data and AD and other dementias-related risk factor data were used to further calculate the age-standardized rates and corresponding 95% confidence intervals (CIs), based on the world standard population reported in GBD 2021 [16]. The age-standardized rates with 95% CI are shown per 100,000 population using the upper equation described in online supplementary Figure 1.
Average annual percentage changes (AAPCs) represent the average increased or reduced rate for the change of a specific variable over a specified period. As for this study, it was used to show the annual change percentage from 1990 to 2021, transformed from the weighted average of the slope coefficient based on the underlying joinpoint regression model [21]. From the abovementioned age-standardized rates with 95% CI, AAPCs were estimated by joinpoint regression to measure the temporal trend [21], using the lower equation described in online supplementary Figure 1. The value of AAPCs demonstrated increase (+), decrease (−), or no change (0) of the percentage annual change during 1990–2021. If AAPCs were >0, the corresponding rate was considered to be in an upward trend. If AAPCs were <0, the corresponding rate was considered to be in a downward trend. Otherwise, the corresponding rate was considered to be unchanged.
The outcome measures are epidemiologically correlated, prevalence, mortality, and DALYs. For example, a mortality reduction in a chronic disease may lead to an increase in both prevalence and DALYs. Thus, more patients lived longer with that disease. Accordingly, an increased number of people with the longer life may promote the higher prevalence in that disease. Thus, the increasing prevalence of AD and other dementias may be explained by the longer life owing to improved medical care. All statistical analyses were performed using GraphPad Prism (version 8.0), Joinpoint Regression Program (version 5.2.0), and R (version 4.4.1).
Results
Global Trends
Globally, the prevalence percentage of AD and other dementias continues to rise (Fig. 1). The prevalence of AD and other dementias increased by 161% between 1990 and 2021, from 21.8 million to 56.9 million. The age-standardized prevalence rate of AD and other dementias increased by 3.27%, from 672 per 100,000 population in 1990 to 694 per 100,000 population in 2021, with an average annual trend of 0.09% (Table 1). Compared with prevalence, the trend of mortality and DALYs from AD and other dementias was less noticeable during the same period. Globally, the percentage of mortality and DALYs from AD and other dementias started descending since 2019 (Fig. 1). The age-standardized mortality from AD was unchanged and maintained 25 per 100,000 population in 1990 and 2021, with an average annual trend of 0% (see online suppl. Table 1). Age-standardized DALYs increased by 1.12%, from 446 per 100,000 population in 1990 to 451 per 100,000 population in 2021, with an average annual trend of 0.01% (see online suppl. Table 2).
Fig. 1.
The percentage changes of global prevalence, mortality, and DALYs of AD and other dementias during 1990–2021.
Table 1.
Age-standardized prevalence and AAPCs of AD and other dementias at global, sex, age, and SDI levels during 1990–2021
| Cases (95% UI) of AD and other dementias in 1990 (×103) | Cases (95% UI) of AD and other dementias in 2021 (×103) | Age-standardized rate (95% UI) in 1990 (per 100,000) | Age-standardized rate (95% UI) in 2021 (per 100,000) | AAPCs (95% CI) | |
|---|---|---|---|---|---|
| Global | 21,800 (19,067 to 24,838) | 56,857 (49,382 to 64,978) | 672 (589 to 764) | 694 (603 to 794) | 0.09 (0.06 to 0.11) |
| Sex | |||||
| Female | 14,143 (12,362 to 16,105) | 36,103 (31,468 to 41,117) | 736 (646 to 834) | 770 (671 to 878) | 0.13 (0.10 to 0.15) |
| Male | 7,656 (6,611 to 8,728) | 20,753 (17,769 to 23,797) | 571 (498 to 654) | 589 (507 to 679) | 0.09 (0.07 to 0.11) |
| Age group | |||||
| <40 years | 0 (0 to 0) | 0 (0 to 0) | 0 (0 to 0) | 0 (0 to 0) | |
| 40–44 years | 53 (23 to 88) | 86 (37 to 147) | 18 (8 to 31) | 17 (7 to 29) | −0.19 (−0.20 to −0.19) |
| 45–49 years | 280 (179 to 416) | 549 (347 to 817) | 121 (77 to 179) | 116 (73 to 173) | −0.11 (−0.12 to −0.11) |
| 50–54 years | 631 (445 to 849) | 1,316 (930 to 1,776) | 297 (209 to 399) | 296 (209 to 399) | −0.01 (−0.01 to 0.00) |
| 55–59 years | 1,059 (827 to 1,337) | 2,345 (1,829 to 2,961) | 572 (447 to 722) | 593 (462 to 748) | 0.11 (0.11 to 0.12) |
| 60–64 years | 1,653 (1,282 to 2,079) | 3,461 (2,684 to 4,381) | 1,029 (798 to 1,295) | 1,081 (839 to 1,369) | 0.15 (0.14 to 0.16) |
| 65–69 years | 2,235 (1,747 to 2,813) | 5,384 (4,186 to 6,722) | 1,808 (1,414 to 2,275) | 1,952 (1,518 to 2,437) | 0.23 (0.21 to 0.26) |
| 70–74 years | 2,835 (2,220 to 3,603) | 7,364 (5,701 to 9,398) | 3,349 (2,622 to 4,255) | 3,578 (2,770 to 4,565) | 0.20 (0.17 to 0.22) |
| 75–79 years | 4,128 (3,310 to 5,066) | 9,325 (7,423 to 11,477) | 6,707 (5,377 to 8,230) | 7,071 (5,629 to 8,702) | 0.15 (0.11 to 0.18) |
| 80–84 years | 4,440 (3,587 to 5,500) | 11,388 (9,081 to 14,175) | 12,552 (10,140 to 15,548) | 13,002 (10,368 to 16,185) | 0.10 (0.06 to 0.12) |
| 85–89 years | 2,990 (2,386 to 3,673) | 9,159 (7,254 to 11,347) | 19,790 (15,790 to 24,310) | 20,032 (15,865 to 24,816) | 0.03 (0.01 to 0.04) |
| 90–94 years | 1,151 (916 to 1,421) | 4,724 (3,711 to 5,912) | 26,857 (21,377 to 33,165) | 26,408 (20,745 to 33,046) | −0.07 (−0.08 to −0.05) |
| ≥95 years | 344 (270 to 428) | 1,755 (1,360 to 2,223) | 33,789 (26,540 to 42,083) | 32,194 (24,954 to 40,786) | −0.16 (−0.17 to −0.16) |
| SDI level | |||||
| High | 8,094 (7,093 to 9,189) | 17,216 (15,033 to 19,546) | 724 (638 to 816) | 709 (620 to 807) | −0.06 (−0.07 to −0.06) |
| High-middle | 5,681 (4,934 to 6,518) | 14,925 (12,861 to 17,156) | 685 (598 to 782) | 766 (660 to 880) | 0.32 (0.26 to 0.34) |
| Middle | 4,832 (4,193 to 5,504) | 16,802 (14,485 to 19,311) | 651 (567 to 744) | 723 (623 to 831) | 0.31 (0.26 to 0.34) |
| Low-middle | 2,350 (2,033 to 2,676) | 6,009 (5,214 to 6,840) | 542 (474 to 616) | 524 (456 to 597) | −0.10 (−0.11 to −0.10) |
| Low | 818 (700 to 930) | 1,855 (1,604 to 2,101) | 540 (471 to 612) | 514 (447 to 584) | −0.15 (−0.16 to −0.15) |
Numbers in parentheses are 95% UI and 95% CI.
AAPCs, average annual percentage changes; AD, Alzheimer’s disease; SDI, sociodemographic index.
Global Trends by Sex
From 1990 to 2021, the age-standardized prevalence of AD and other dementias increased for both women and men worldwide (women: from 0.736 million to 0.77 million; men: from 0.571 million to 0.589 million). The increase in AD and other dementia prevalence was more rapid among women than among men (AAPCs: 0.13% vs. 0.09%) (Table 1). During the same period, the age-standardized mortality from AD and other dementias also increased for both men and women, although the increased rate was smaller in women than that in men (AAPCs: 0.02% vs. 0.08%) (see online suppl. Table 1). In 1990, women had higher DALYs from AD and other dementias than men (495 vs. 363 per 100,000 population). In 2021, DALYs from AD and other dementias increased in men and women (505 vs. 373 per 100,000 population), with an average annual trend of 0.07% versus 0.05% (see online suppl. Table 2).
Global Trends by Age Subgroup
Globally, the prevalence of AD and other dementias obviously increased in every age subgroup (40–44 years: from 0.05 million to 0.09 million; 45–49 years: from 0.28 million to 0.55 million; 50–54 years: from 0.63 million to 1.32 million; 55–59 years: from 1.06 million to 2.35 million; 60–64 years: from 1.65 million to 3.46 million; 65–69 years: from 2.2 million to 5.4 million; 70–74 years: from 2.8 million to 7.4 million; 75–79 years: from 4.1 million to 9.3 million; 80–84 years: from 4.4 million to 11.4 million; 85–89 years: from 3.0 million to 9.2 million; 90–94 years: from 1.2 million to 4.7 million; ≥95 years: from 0.3 million to 1.8 million) during 1990–2021 (Table 1). This increased trend was more obvious (from 1.6 folds in 40–44 years to 5.1 folds in ≥95 years), as age increased. The age-standardized prevalence of AD and other dementias increased during 55–89 years and mostly increased (AAPC: 0.23%) in 65–69 years during 1990–2021. The age-standardized mortality of AD and other dementias mostly increased (AAPC: 0.08%) in 40–45 years during 1990–2021 (see online suppl. Table 1). The rising trend of the mortality rates for AD and other dementias gradually reduced as ages increased. DALYs of AD and other dementias increased during 50–84 years and mostly increased (AAPC: 0.12%) in 65–69 years during 1990–2021 (see online suppl. Table 2).
Relative to the overall AD and other dementias, the proportion of AD and other dementias among people aged ≥55 years has shown a consistent increase from 95.6% in 1990 to 96.6% in 2021 (see online suppl. Fig. 2). Compared with the overall AD and other dementias, AD and other dementias among those aged ≥55 years had noticeably increased in prevalence, mortality, and DALYs from 1990 to 2021 (see online suppl. Fig. 3). The disease burden including mortality and DALYs from AD and other dementias has been increasing over the past 32 years mainly in the population aged ≥55 years (see online suppl. Fig. 4). In all age subgroups, the upward or downward trend of prevalence, mortality, and DALYs from 1990 to 2021 was similar in men to that in women (see online suppl. Fig. 5).
Global Trends by SDI
Globally, the prevalence of AD and other dementias at least doubly increased across all subgroups of SDI (high: from 8.1 million to 17.2 million; high-middle: from 5.7 million to 14.9 million; middle: from 4.8 million to 16.8 million; low-middle: from 2.4 million to 6.0 million; low: from 0.8 million to 1.9 million) during 1990–2021 (Table 1). The age-standardized prevalence of AD and other dementias similarly increased (AAPCs: 0.32% vs. 0.31%) in countries with a high-middle and middle SDI and decreased in countries with a high, low-middle, and low SDI (AAPCs: −0.06%, −0.10%, −0.15%, respectively). While the age-standardized mortality from AD and other dementias decreased (AAPC: −0.06%) in countries with a high SDI during the same period, it increased in countries with a high-middle, middle, low-middle, and low SDI (AAPCs: 0.05%, 0.10%, 0.41%, and 0.41%, respectively) from 1990 to 2021 (see online suppl. Table 1). The increased trend gradually intensifies as SDI becomes low. Similar to trend in the age-standardized mortality, the changed trend in the age-standardized DALYs from AD and other dementias is from decreased to gradually increased in countries with a high, high-middle, middle, low-middle, and low SDI (AAPCs: −0.10%, 0.10%, 0.13%, 0.24%, and 0.23%, respectively) (see online suppl. Table 2).
Regardless of SDI level, the change in the burden of diseases including mortality and DALYs was similar in women to that in men (see online suppl. Fig. 6 and 7). Regardless of SDI level, the increase in prevalence, mortality, and DALYs among those aged ≥55 years has consistently been higher than in the overall population (see online suppl. Fig. 8 and 9). The upward trend in prevalence, mortality, and DALYs for AD and other dementias among those aged ≥55 years became more pronounced after surpassing an SDI threshold of 0.7 (see online suppl. Fig. 10).
Regional Trends
From 1990 to 2021, East Asia and high-income Asia Pacific of the 21 regions showed an increase (AAPCs: 0.72% vs. 0.15%) in prevalence of AD and other dementias, whereas the other 19 regions showed a reduction (see online suppl. Table 3; online suppl. Fig. 11). In 2021, among the 21 regions, the highest age-standardized prevalence for AD and other dementias was in high-income Asia Pacific (811 per 100,000 population), western Europe (802 per 100,000 population), and high-income North America (785 per 100,000 population) (see online suppl. Table 3). No difference was observed after sex stratification (see online suppl. Table 4).
Most regions experienced a reduction in mortality from AD and other dementias at various rates during 1990–2021, whereas a large increase in mortality was found in six regions including South Asia (AAPC: 0.68%), Central Sub-Saharan Africa (AAPC: 0.25%), and South Asia (AAPC: 0.20%) (see online suppl. Table 5; online suppl. Fig. 11). The largest reduction in mortality from AD and other dementias was in Oceania (AAPC: −0.28%). In 2021, the highest age-standardized mortality for AD and other dementias was in Central Sub-Saharan Africa (35 per 100,000 population), East Asia (30 per 100,000 population), and high-income North America (28 per 100,000 population) (see online suppl. Table 5). After stratifying by sex, no significant differences were found (see online suppl. Fig. 12).
Most regions experienced a reduction in DALYs from AD and other dementias at various rates during 1990–2021, whereas a large increase in DALYs was found in six regions including South Asia (AAPC: 0.42%), Central Sub-Saharan Africa (AAPC: 0.32%), Eastern Sub-Saharan Africa (AAPC: 0.22%) (see online suppl. Table 6; online suppl. Fig. 11). The largest reduction in DALYs from AD and other dementias among older people was in Australasia (AAPC: −0.29%). In 2021, the highest age-standardized DALYs for AD and other dementias were in Central Sub-Saharan Africa (591 per 100,000 population), East Asia (559 per 100,000 population), and Tropical Latin America (503 per 100,000 population) (see online suppl. Table 6). After stratifying by sex, no significant differences were found (see online suppl. Fig. 12).
National Trends
In 2021, People’s Republic of China had the highest age-standardized prevalence of AD and other dementias (901 per 100,000 population), followed by Lebanese Republic (828 per 100,000 population) and Federal Republic of Germany (821 per 100,000 population) (online suppl. Table 7). From 1990 to 2021, People’s Republic of China had the highest increase in age-standardized prevalence of AD and other dementias, with an average annual trend of 0.75%, followed by Taiwan (Province of China) (AAPC: 0.30%) and Republic of Italy (AAPC: 0.30%) (Fig. 2; online suppl. Table 7). Over the same period, Kingdom of Denmark showed the most substantial decrease (AAPC: −0.69%), followed by Kingdom of Norway (AAPC: −0.59%) and Australia (AAPC: −0.56%).
Fig. 2.
Map showing AAPCs in global prevalence of AD and other dementias during 1990–2021.
Both Gabonese Republic and Democratic Republic of the Congo had the highest age-standardized mortality of AD and other dementias (35 per 100,000 population), followed by Republic of the Congo (34 per 100,000 population) in 2021 (online suppl. Table 7). From 1990 to 2021, Republic of India had the highest increase in age-standardized mortality of AD and other dementias (AAPC: 0.92%), followed by Republic of Indonesia (AAPC: 0.83%) and Kingdom of Bhutan (AAPC: 0.79%) (Fig. 3; online suppl. Table 7). Over the same period, Guam showed the most substantial decrease (AAPC: −0.84%), followed by Republic of Korea (AAPC: −0.68%) and United Arab Emirates (AAPC: −0.66%).
Fig. 3.
Map showing AAPCs in global mortality among people with AD and other dementias during 1990–2021.
Democratic Republic of the Congo had the highest age-standardized DALYs of AD and other dementias (600 per 100,000 population), followed by Gabonese Republic (588 per 100,000 population) and Islamic Republic of Afghanistan (578 per 100,000 population) in 2021 (online suppl. Table 7). From 1990 to 2021, Republic of India had the highest increase in age-standardized DALYs of AD and other dementias (AAPC: 0.51%), followed by Republic of Indonesia (AAPC: 0.47%) and Republic of Uganda (AAPC: 0.46%) (Fig. 4; online suppl. Table 7). Over the same period, United Arab Emirates showed the most substantial decrease (AAPC: −0.57%), followed by Republic of Korea (AAPC: −0.49%) and Guam (AAPC: −0.41%).
Fig. 4.
Map showing AAPCs in global DALYs among people with AD and other dementias during 1990–2021.
Risk Factors
Based on the analysis of global data from 1990 to 2021, three primary risk factors, including high fasting plasma glucose, high body mass index, and smoking, were revealed to be associated with DALYs for AD and other dementias (Table 2). Globally, these factors accounted for 66 DALYs per 100,000 people, 33 DALYs per 100,000 people, and 18 DALYs per 100,000 people, respectively, in 2021. From 1990 to 2021, the corresponding AAPCs for these factors were 1.12%, 1.38%, and −0.80%. Regardless of SDI level, the substantial increased burden from 1990 to 2021 was associated with a high fasting plasma glucose and high body mass index. Countries with a low-middle SDI had the highest increased high fasting plasma glucose (AAPC: 1.53%), whereas countries with a low SDI had the highest increased high body mass index (AAPC: 4.16%). In contrast, regardless of SDI level, smoking, contributed to DALYs burden from 1990 to 2021, had a substantial reduction. The countries with a high SDI were the most substantially decreased (AAPC: −1.23%).
Table 2.
Main risk factors for age-standardized AD and other dementias-related DALYs and their AAPCs during 1990–2021
| Risk factors by SDI | Age-standardized DALYs (per 100,000) (95% UI) | AAPCs (95% CI) | |
|---|---|---|---|
| 1990 | 2021 | ||
| High fasting plasma glucose | |||
| Global | 47 (3 to 126) | 66 (4 to 179) | 1.12 (1.11 to 1.14) |
| High SDI | 51 (3 to 135) | 75 (4 to 199) | 1.25 (1.23 to 1.26) |
| High-middle SDI | 46 (3 to 125) | 64 (4 to 171) | 1.10 (1.08 to 1.12) |
| Middle SDI | 48 (3 to 134) | 63 (4 to 173) | 0.88 (0.86 to 0.89) |
| Low-middle SDI | 36 (2 to 96) | 57 (3 to 159) | 1.53 (1.52 to 1.54) |
| Low SDI | 34 (2 to 94) | 49 (3 to 140) | 1.19 (1.17 to 1.21) |
| High body mass index | |||
| Global | 21 (−1 to 80) | 33 (−6 to 115) | 1.38 (1.37 to 1.39) |
| High SDI | 32 (−4 to 116) | 43 (−9 to 146) | 0.92 (0.91 to 0.93) |
| High-middle SDI | 26 (−2 to 97) | 40 (−8 to 138) | 1.41 (1.40 to 1.42) |
| Middle SDI | 8 (0 to 37) | 26 (−4 to 95) | 3.71 (3.69 to 3.72) |
| Low-middle SDI | 6 (0 to 29) | 17 (−2 to 64) | 3.29 (3.27 to 3.32) |
| Low SDI | 3 (−1 to 17) | 10 (0 to 44) | 4.16 (4.15 to 4.18) |
| Smoking | |||
| Global | 23 (10 to 54) | 18 (8 to 42) | −0.80 (−0.83 to −0.78) |
| High SDI | 28 (12 to 65) | 19 (8 to 43) | −1.23 (−1.25 to −1.22) |
| High-middle SDI | 23 (9 to 52) | 22 (10 to 49) | −0.12 (−0.16 to −0.08) |
| Middle SDI | 24 (10 to 57) | 19 (8 to 45) | −0.72 (−0.77 to −0.69) |
| Low-middle SDI | 16 (7 to 38) | 13 (5 to 31) | −0.65 (−0.67 to −0.63) |
| Low SDI | 10 (4 to 23) | 8 (3 to 19) | −0.59 (−0.60 to −0.58) |
Numbers in parentheses are 95% UI and 95% CI.
AD, Alzheimer’s disease; DALYs, disability-adjusted life-years; AAPCs, average annual percentage changes; SDI, sociodemographic index.
Discussion
The age-standardized prevalence of global AD and other dementias increased, concomitant with an unchanged ratio of the age-standardized mortality and a slightly increased ratio of the age-standardized DALY during 1990–2021. Inequality was identified by age, SDI, region, and country. While the highest prevalence remained in population aged 65–69 and the countries with a high-middle SDI such as East Asia (e.g., China), the highest mortality and DALYs were found in population aged 65–69 and the countries with a low-middle SDI such as South Asia (e.g., India). High fasting plasma glucose ranked the highest risk factor for DALYs during 1990–2021. Optimal blood glucose control remains challenging for prevention of AD and other dementias. My study extends the present understanding of the increasing global burden of AD and other dementias by adding the data in the recent 3 years (2019–2021) from GBD 2021. My findings will play an important role in the future research and health practice by providing optimistic evidence for global burden of AD and other dementias.
Comparison with Previous Related Research
Based on GBD 2015, the percentage changes between 1990 and 2015 in age-standardized prevalence, mortality, and DALYs of AD and other dementias have been reported to be 2.4% (1.7 to 3.2), −3.4% (−4.8 to −1.4), and −5.7% (−7.2 to −4.2), respectively [22]. Based on GBD 2016, the percentage changes between 1990 and 2016 in age-standardized prevalence, mortality, and DALYs of AD and other dementias have been reported to be 1.7% (1.0 to 2.4), 3.6% (1.1 to 5.6), and 2.1% (0.1 to 3.8), respectively [6]. Another study, based on GBD2016, reported that the percentage changes between 1990 and 2016 in age-standardized prevalence, mortality, and DALYs of AD and other dementias were 2% (1 to 2), 4% (1 to 6), and 2% (0 to 4), respectively [23]. Based on GBD 2019, Li X et al. [15] reported that the annual percentage changes between 1990 and 2019 in age-standardized prevalence, mortality, and DALYs of AD and other dementias were 0.2% (0.18 to 0.21), 0.13% (0.1 to 0.15), and 0.15% (0.13 to 0.16), respectively. Based on the same GBD datasets, Javaid et al. [8] found that the total number of persons affected had more than doubled from 1990 to 2019 and dementia metrics showed a continuous increase in prevalence, incidence, mortality, and DALYs rates worldwide during the last 3 decades. Based on the same GBD datasets, Su et al. [24] demonstrated that the global incidence of AD and other dementias increased from 507.96 per 100,000 in 1990 to 569.39 per 100,000 in 2019, showing a significant increase in this period. By focusing on Middle East and North Africa region in GBD 2019 datasets, Safiri et al. [25] found that the point prevalence of AD and other types of dementia has increased over the past 3 decades, and the corresponding regional burden was higher than the global average in 2019. I here reported that the AAPCs during 1990–2021 in age-standardized prevalence, mortality, and DALYs of AD and other dementias were 0.09% (0.06 to 0.11), 0.00% (−0.01 to 0.02), and 0.01% (0.00 to 0.03), respectively. Compared with the previous data, my data suggest that prevalence, mortality, and DALYs of AD and other dementias present a new change trend. While the increase slowed down in the prevalence of AD and other dementias, the mortality no longer increased and DALY only slightly increased during 1990–2021. Noticeably, although the prevalence percentage of AD and other dementias continues to rise, the percentage of mortality and DALYs from AD and other dementias started descending since 2019.
Age Differences in Burden of AD and Other Dementias
My study found that the most significant increase in prevalence and DALYs of AD and other dementias was observed among population aged 65–69 years during 1990–2021. The increased trend gradually decreased from 65 to 69 years old to both ends. Even, there is a downward trend among both ends of the population aged 40–49 and ≥90 years. Thus, I should pay more attention to AD and other dementias among population aged 65–69 years and even allocate more medical resources to prevent and treat these population. Additionally, in terms of absolute quantity, the number of prevalence, mortality, and DALYs of AD and other dementias rapidly increased with age. Furthermore, the ratio of prevalence, mortality, and DALYs of AD and other dementias among population aged ≥55 years has a considerably high proportion in overall AD and other dementias (96.60% in 2021), still on the rise every year during 1990–2021. Populations worldwide are aging, and caring for older people with AD and other dementias involves both healthy aging and management of AD and other dementias.
Sociodemographic Differences in Burden of Older People with AD
I found that the change of the age-standardized prevalence, mortality, and DALYs of AD and other dementias was unequal between countries. First, I observed that all of the prevalence, mortality, and DALYs of AD and other dementias decreased in countries with a high SDI. The reduction may attribute to good education, economic conditions, and medical resources. A previous study has shown that cardiovascular disease was associated with increased AD and other dementias-related mortality rates [26]. Thus, in recent years, the medical control of vascular risk factors (especially hypertension and diabetes) is likely to be a key factor for the decreased prevalence, mortality, and DALYs of AD and other dementias in countries with a high SDI. Second, the prevalence of AD and other dementias most significantly increased in the countries with a high-middle SDI, especially China from East Asia. China has experienced the most remarkably rising trend of prevalence of AD and other dementias during 1990–2021 and has the largest population of people with dementia in the world [2]. Finally, the most significant increase in AD and other dementias-related mortality and DALYs was observed in the countries with a low-middle SDI, especially India from South Asia. As the SDI decreased, the burden of AD and other dementias among older people appeared to gradually increase. This aligns a shortage of medical resources due to the large population growth.
Risk Factors in Burden of AD and Other Dementias
The key issue to underline is the huge burden due to AD and other dementias worldwide. There is no effective pharmaco-therapy. The only way right now is to prevent and focus on lifestyle risk factors and control of medical comorbidities. High fasting plasma glucose was identified to be a major risk factor for DALYs from AD and other dementias. A previous study showed that among participants with diabetes, a high average glucose level was related to dementia risk [27]. Even among persons without diabetes, a high glucose level may also be a risk factor for dementia [27]. In addition, a Mendelian randomization study provided causal association of glycemic traits, especially high fasting glucose, with the high risk of AD [28]. Thus, a high fasting plasma glucose level has been one well-established risk factor [29]. My data demonstrated that from 1990 to 2021, high fasting plasma glucose-related DALYs from AD and other dementias still increased (AAPCs: 1.12% [1.11 to 1.14]). I therefore suggest that management of high fasting plasma glucose should be used to be a potential preventive and therapeutic intervention for AD and other dementias.
Additionally, I found that high body mass index was the second important risk factor for DALYs from AD and other dementias. However, the association between body mass index and AD remains controversial [30]. A limited number of observational studies showed that high body mass index was associated with dementia risk [31–33]. On the contrary, higher body mass index was linked to lower dementia risk by the largest meta-analysis [34]. My data demonstrated that from 1990 to 2021, high body mass index-related DALYs from AD and other dementias still increased (AAPCs: 1.38% [1.37 to 1.39]). Thus, my study supported current clinical guidelines for dementia prevention: obesity has been regarded as one modifiable risk factor [35, 36].
Finally, I found that smoking was the third important risk factor for DALYs from AD and other dementias. Overall, former or active smoking is related to a significantly increased risk for AD [37]. Current smoking increases risk of AD and may increase risk of other dementias [38]. WHO global report on trends in prevalence of tobacco use 2000–2030 showed that the global tobacco usage rate is showing a downward trend, dropping from 29.4% in 2000 to 22.3% in 2020, and is expected to decrease to 20.9% by 2025. My data showed that from 1990 to 2021, smoking-related DALYs from AD and other dementias decreased (AAPCs: −0.80% [−0.83 to −0.78]). This reinforces smoking cessation needed for dementia-related DALYs reduction.
Application of This Study to Clinical Practice and Policymaking
Noticeably, the percentage of mortality and DALYs from AD and other dementias started descending since 2019. It is encouraging. Thus, policymakers will aid to further reduce mortality and DALYs from AD and other dementias by rational allocation of health resources and the provision of targeted guidelines. In addition, while the highest prevalence remained in population aged 65–69, the highest mortality and DALYs were found in population aged 65–69. Thus, health resource preparedness is needed for the growing population aged 65–69. Finally, while the highest prevalence remained in the countries with a high-middle SDI such as East Asia (e.g., China), the highest mortality and DALYs were found in the countries with a low-middle SDI such as South Asia (e.g., India). Thus, policymakers from the countries with a high-middle SDI such as East Asia (e.g., China) and a low-middle SDI such as South Asia (e.g., India) should make policy to reduce the prevalence and mortality and DALYs, respectively.
In clinical practice, AD and other dementias-risk population are encouraged to take active control of their blood glucose, high body mass index, and smoking. These population should develop self-management skills and even be reinforced in guidelines. Suitable training is also required for doctors and caregivers. For future research, more innovative studies are needed to help people with AD and other dementias by providing the cost-effective treatment and care.
The Limitations of This Study
My study has several limitations. First, my data, originated from the existing epidemiological data, were used to generate estimates for AD and other dementias by modeling processes such as DisMod-MR 2.1 model. The estimated results require caution in the application of the real world. Second, the choice of models and parameter settings in modeling processes could have influenced the results. Third, although I used rigorous statistical methods, variations in data collection and precession across countries and regions may potentially lead to the reduced accuracy of the results. Fourth, the data from GBD during 1990–2021, especially from 2021, exist a time lag. Finally, the diagnosis of AD and other dementias, medical practices, healthcare policies, and healthcare systems across countries may have an effect on disease burden. Thus, to validate my findings, high-quality real-world research will be needed.
Conclusions
The global increased prevalence of AD and other dementias may partly be attributed to population aged 65–69 in the countries with a high-middle SDI (e.g., China), whereas mortality and DALY ratio of population aged 65–69 from the countries with a low-middle SDI (e.g., India) is most significantly growing. Controlling of DALYs-associated risk factors such as high fasting plasma glucose, high body mass index, and smoking may be needed for the reduction of AD and other dementias-related DALYs.
Acknowledgments
The author appreciates the individuals who contributed to the 2021 GBD Study.
Statement of Ethics
The Medical Ethics Committee of Beijing Institute of Brain Disorders at Capital Medical University determined that this study did not require approval because it used publicly available data. Written informed consent (from participants) was not needed for this study as the data used are publicly available.
Conflict of Interest Statement
The author has no conflicts of interest to declare.
Funding Sources
This work was supported by Chinese Institutes for Medical Research, Beijing (Grant No. CX24PY07), R&D Program of Beijing Municipal Education Commission (KZ202210025035), and National Natural Science Foundation of China (32270933).
Author Contributions
R.W. conceived and designed the study, collected data, performed the statistical analysis, interpreted data, drafted and revised the manuscript, and approved the final version before submission.
Funding Statement
This work was supported by Chinese Institutes for Medical Research, Beijing (Grant No. CX24PY07), R&D Program of Beijing Municipal Education Commission (KZ202210025035), and National Natural Science Foundation of China (32270933).
Data Availability Statement
All research data in this work are obtained from the GBD 2021 (http://ghdx.healthdata.org/gbd-results-tool).
Supplementary Material.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
All research data in this work are obtained from the GBD 2021 (http://ghdx.healthdata.org/gbd-results-tool).
