Global, Regional and Country-Specific Burden of Dementia Associated with Depression Across the Life-course

• Global PAF for dementia due to MDD was 4.8% using 2024 estimates • PAFs were highest in low-SDI regions, exceeding 10% in some countries • Women had consistently higher attributable risk than men across all strata • Mid-life depression contributed substantially to dementia burden Mid- and late-life depression are associated with increased dementia risk. This study quantified the global burden of dementia attributable to major depressive disorder (MDD) and identified geographic and demographic variations across the life-course. We used Global Burden of Disease (GBD) 2021 data across 204 countries to estimate MDD prevalence and evaluate its association with dementia risk. We examined whether associations varied by early adulthood (20-39 years), mid-life (40-54 years), late mid-life (55-69 years), and late-life (70+ years) age groups, sex, and Socio-demographic Index (SDI) classifications. Population-attributable fractions (PAFs) and potential impact fractions (PIFs) were calculated using relative risk (RR) estimates from the 2020 (RR=1.90) and 2024 (RR=2.25) Lancet Commission on Dementia. MDD prevalence was consistently higher among women than men across all regions and age groups, ranging from 4.42%-5.11% in women versus 2.87%-3.41% in men. Using the 2024 Lancet Commission RR, the mean global PAF for dementia associated with MDD was 4.81% (95% uncertainty interval (UI): 2.75%-7.48%), with substantial geographic variations. The highest PAFs were observed in sub-Saharan Africa, exceeding 10% in several countries. Low-SDI regions had higher PAFs (6.74%, 95% UI: 3.89%–10.40%) than high-SDI regions (4.49%, 95% UI: 2.56%–6.98%). PIF estimates varied across SDI regions, indicating that higher burden does not translate to greater reduction potential under the specified counterfactual. Results demonstrate substantial global inequities in depression-associated dementia risk, with highest burden concentrated in low- and middle-income countries, highlighting the critical need for strengthened mental health systems in resource-limited settings.