Epidemiological trends and cross-country inequalities in the global burden of Alzheimer's disease and other dementias in postmenopausal women from 1990 to 2021

To evaluate the trends, cross-country inequalities, and risk factors associated with Alzheimer's disease and other dementias (ADOD) in postmenopausal women globally, and project the disease burden to 2050. The age-standardized rates (ASRs) and 95% uncertainty intervals (UIs) of prevalence, incidence, mortality, and disability-adjusted life-years (DALYs) for ADOD among postmenopausal women were estimated by using the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2021 data. The average annual percentage change (AAPC) was calculated using joinpoint regression. A decomposition analysis was performed to quantify the contributions of population growth, aging, and epidemiologic changes. The slope index of inequality (SII) and concentration index, as recommended by the World Health Organization, were used to evaluate the cross-country inequalities in ADOD burden. The ADOD burden among postmenopausal women to 2050 was projected using the Bayesian age-period-cohort analysis (BAPC) model. Risk factor attribution was quantified according to GBD methodology. In 2021, the estimated global ASRs of prevalence, incidence, mortality, and DALYs of ADOD among postmenopausal women were 4414.52 (95%UIs: 3492.78, 5504.77), 751.18 (95%UIs: 517.67, 1019.3), 164.29 (95%UIs: 41.79, 425.37), and 2935.7 (95%UIs: 1349.85, 6306.48) per 100000 population, respectively. East Asia recorded the highest total number of cases and the highest ASRs of prevalence and incidence, while Central Sub-Saharan Africa showed the highest ASRs of mortality and DALYs. From 1990–2021, the ADOD burden increased most rapidly during 2019–2021. Population growth (82.07% contribution) and aging (12.48%) were the primary drivers of increases in global DALYs. SDI-related inequalities escalated over time, with the SII increasing from 1275.06 95% confidence interval (CI): 1037.55, 1512.57 in 1990 to 1697.71 (95%CI: 1430.70, 1964.73) in 2021. The BAPC model showed that both the ASRs and case number of prevalence, incidence, mortality, and DALYs were predicted to increase from 2022 to 2050, with predicted ASRs of 6067.51 95% credible interval (CrI): 2149.42, 9985.60, 1052.37 (95%CrI: 361.2, 1743.54), 186.15 (95%CrI: 90.01, 282.3), and 3602.34 (95%CrI: 1530.01, 5674.67) per 100,000 population in 2050. High fasting plasma glucose was identified as the leading risk factor contributing to ADOD burden. From 1990 to 2021, there was an overall upward trend in the global burden of ADOD among postmenopausal women. Driven by demographic shifts (population growth and aging) and metabolic risks (particularly high fasting plasma glucose), the burden of postmenopausal women with ADOD is expected to increase substantially. Postmenopausal women in higher SDI countries bore a disproportionately higher ADOD burden, and the SDI-related inequalities among countries widened during the study period. These findings highlight major challenges in the prevention, control, and management of ADOD in postmenopausal women. Health authorities should shift from reactive treatments to proactive prevention, emphasizing the establishment of targeted health policies, glucose control, and optimizing medical resource allocation to meet the heterogeneous needs of this vulnerable population. • "Demographic Hegemony" drives the global burden: Decomposition analysis reveals that population growth and aging have mathematically outpaced the "prevention dividend" of declining incidence rates. • Developmental Paradox in inequality: Contrary to typical disease patterns, the burden is disproportionately concentrated in High-SDI regions, driven by the metabolic transition in surviving older cohorts. • Estrogen-Glucose Axis vulnerability: High fasting plasma glucose emerges as the primary modifiable risk factor, reflecting the loss of estrogen-mediated metabolic resilience. • 2050 Projections indicate a resource crisis: There was an increasing trend both in the ASRs and case number of prevalence, incidence, deaths, and DALYs of ADOD from 2022 to 2050, necessitating a shift from passive care to precision prevention. • Recent Syndemic Surge (2019-2021): A distinct acceleration in burden metrics coincided with the COVID-19 pandemic, suggesting a "syndemic" interaction between viral stress and neurodegeneration.