Background: Anticholinergic burden (AB) is linked to adverse health outcomes and mortality among older adults. Yet, the national trends in AB and its long-term mortality risk are not well-defined.

Methods: We analysed data from 16 188 older adults in the National Health and Nutrition Examination Survey (NHANES) spanning 32 years. AB was assessed using the 2023 American Geriatrics Society Beers Criteria® and four validated scales (ARS, ADS, ACB and ACSBC). Age-standardised prevalence trends were examined using survey-weighted logistic regression. Mortality outcomes were ascertained through linkage to the National Death Index and analysed with Cox proportional hazards models to estimate adjusted hazard ratios (HRs).

Results: From 1988-94 to 2017-March 2020, the prevalence of any strong anticholinergic medication use and high AB (score ≥ 3) declined significantly across all scales (all PTrend < .05). During a median follow-up of 81 months, 9006 deaths (49.3%) occurred. After comprehensive adjustment for covariates, high AB was independently associated with elevated all-cause mortality (ADS: HRs 1.65, 95% CI 1.51-1.81; ACB: HRs 1.54, 95% CI 1.41-1.68), cardiovascular mortality (ADS: HRs 1.94, 95% CI 1.71-2.20; ACB: HRs 1.66, 95% CI 1.46-1.88) and cancer mortality (ADS: HRs 1.40, 95% CI 1.18-1.68; ACB: HRs 1.31, 95% CI 1.09-1.57).

Conclusions: While the prevalence of AB among US older adults has declined over the past three decades, high exposure remains a strong, independent predictor of all-cause, cardiovascular and cancer mortality. These findings highlight the ongoing need for safer prescribing and sustained deprescribing initiatives in geriatric care.