Global burden, spatiotemporal disparities, and sex-specific trends of early- and late-onset Alzheimer's disease and other dementias: a comparative analysis and projections to 2035.

INTRODUCTION: Early-onset Alzheimer's disease and other dementias (EOAD) and late-onset Alzheimer's disease and other dementias (LOAD) represent significant global disease burden challenges. However, previous studies have frequently overlooked differences in their spatial distribution, population characteristics, temporal trends, and healthcare demands. This study aims to systematically compare the burden of EOAD and LOAD at global and regional levels from 1990 to 2021, analyzing disparities in spatial patterns, demographic features, and temporal trajectories, while projecting future trends. METHODS: Data were extracted from the GBD 2021 database. EOAD was defined as age-standardized cases among individuals aged 40-64 years, and LOAD as those aged ≥ 65 years. Primary outcomes included incidence, mortality, and disability-adjusted life years (DALYs). Analyses covered global, Socio-Demographic Index (SDI) regions, and 21 regions from 1990 to 2021. Bayesian age-period-cohort (BAPC) modeling projected disease burdens to 2035. RESULTS: In 2021, LOAD demonstrated a substantially higher global burden than EOAD: incidence cases (8,455,150 [95% UI: 5,818,063-11,461,560] vs. 1,381,906 [894,768-1,963,453]), mortality cases (1,879,291 [471,472-4,968,222] vs. 73,386 [14,059-232,170]), and DALYs (32,558,570 [14,907,368-71,154,572] vs. 3,774,117 [1,696,439-8,881,154]). LOAD exhibited stronger female predominance globally compared to EOAD. From 1990 to 2021, LOAD burden showed an initial decline followed by resurgence, stabilizing overall, while EOAD displayed persistent gradual growth. EOAD had higher annualized percentage changes (AAPC) than LOAD: incidence (0.18% [95% CI: 0.14-0.21] vs. 0.03% [-0.02-0.07]), mortality (0.07% [0.04-0.10] vs. 0.01% [-0.02-0.04]), and DALYs (0.07% [0.05-0.09] vs. 0.03% [-0.00-0.06]). BAPC projections indicated LOAD burden will remain significantly higher than EOAD by 2035. Geographically, East Asia reported the highest absolute burden for both conditions, while Central Sub-Saharan Africa and Tropical Latin America showed peak ASIR, ASMR and AS-DALYs. South Asia exhibited the fastest growth rates. CONCLUSION: EOAD and LOAD demonstrate distinct spatial distributions, sex-specific patterns, and temporal trends. Differentiated strategies targeting these two conditions are urgently needed to achieve precision public health goals.