Associations between low-dose drinking water lithium exposure and Dementia: A nationwide U.S. ecological study.

Lithium is a naturally occurring trace element with established neuroprotective and psychotropic properties at pharmacologic doses. Dementia is one of the most burdensome neuropsychiatric conditions in the United States. Although several epidemiological studies have examined associations between lithium in drinking water and dementia outcomes, findings remain inconsistent. We examined county-level associations between drinking water lithium concentrations and dementia prevalence, incidence, and mortality across the United States. Population-weighted lithium concentrations were estimated using data from the U.S. Environmental Protection Agency's Fifth Unregulated Contaminant Monitoring Rule (UCMR 5), which covers public water systems serving approximately 70.5% of the U.S. population. County-level dementia diagnoses and all-cause mortality among individuals with dementia were obtained from the U.S. Dementia DataHub, encompassing the entire Medicare population (∼62 million beneficiaries). We applied quasi-Poisson regression within generalized additive mixed models, including sex-stratified analyses. Compared with counties with low lithium concentrations, those with high concentrations had lower dementia prevalence (prevalence ratio [PR] = 0.965, 95% CI: 0.950, 0.981) and incidence (incidence rate ratio [IRR] = 0.958, 95% CI: 0.939, 0.978), exhibiting non-linear dose-response patterns. In contrast, all-cause mortality among individuals with dementia was higher in high-lithium counties (mortality rate [MR] = 1.017, 95% CI: 1.007, 1.027), although this association was largely attenuated after stratification by county-level Hispanic population percentage. These findings suggest inverse associations between low-level drinking water lithium concentrations and county-level dementia prevalence and incidence, while associations with mortality remain uncertain. Further studies incorporating individual-level data are needed to clarify the health effects of trace lithium exposure.