Sex-specific contribution of Alzheimer's disease to mortality in the United States

ObjectivesTo assess whether the burden of mortality attributable to Alzheimers dementia in the US for women and men. MethodsData came from 3,491 women and 1,160 men ages 65 and older (mean 76.5 for both sexes) with no dementia at baseline from five longitudinal cohort studies of aging with identical annual diagnostic assessments of dementia. Mortality hazard ratios (HR) after incident Alzheimers dementia were estimated per 10-year age strata from proportional hazard models. Population attributable risk percent (PAR%) was derived to estimate excess mortality after a diagnosis of incident Alzheimers dementia. Results were then stratified by self-reported sex, and separately with an interaction term for sex by incident Alzheimers dementia. The number of excess deaths attributable to Alzheimers dementia in the US for women and men by age group was then estimated. ResultsOver an average of 9 (SD=5.8) years, 954 (27.3%) women and 316 (27.2%) men without dementia at baseline developed Alzheimers dementia; 1,792 (51.3%) women and 726 (62.6%) men died. In a model with terms for sex, race, education, incident Alzheimers dementia, and interaction between male sex and Alzheimers dementia, we observed an interaction (HR = 1.24, 95% CI: 1.00, 1.53) in the age strata 85+, indicating a higher risk of mortality due to Alzheimers dementia for men; at lower ages the interaction was opposite (HR = 0.75, 95% CI: 0.52, 1.09 in age strata 75-84), indicating higher risk of mortality from Alzheimers dementia for females. After further adjusting for vascular risk factors and diseases, the interactions were similar. PAR% was similar for age 85+ for women and men (33.4% and 32.9% respectively) but higher for women than men in the age strata 75-84 (24.2% and 19.1%). In 2023, we estimate 465,400 deaths--271,700 in women and 193,700 in men--were attributable to Alzheimers dementia. Adjusted PAR%s that took account of differences in vascular risk factors and disease showed even larger gaps for women compared to men (41.3% vs 37.5% for age 85+ and 33.2% vs 16.3% for age 75-84), resulting in estimates of 349,409 deaths from AD for women and 198,724 for men. ConclusionsThe number of deaths attributable to Alzheimers dementia is estimated to be 270,000-350,000, making it one of the leading causes of death in women, on par with cancer. The number is about 200,000 in men which also makes it a leading cause of death, on a par with accidents but much lower than cancer.