Examining the Relationship between Trace Lithium in Drinking Water and the Rising Rates of Age-Adjusted Alzheimer's Disease Mortality in Texas

Abstract

Background: Alzheimer's disease (AD) mortality rates have steadily increased over time. Lithium, the current gold standard treatment for bipolar disorder, can exert neuroprotective effects against AD.

Objective: We examined the relationship between trace levels of lithium in drinking water and changes in AD mortality across several Texas counties.

Methods: 6,180 water samples from public wells since 2007 were obtained and averaged for 234 of 254 Texas counties. Changes in AD mortality rates were calculated by subtracting aggregated age-adjusted mortality rates obtained between 2000-2006 from those obtained between 2009-2015. Using aggregated rates maximized the number of counties with reliable mortality data. Correlational analyses between average lithium concentrations and changes in AD mortality were performed while also adjusting for gender, race, education, rural living, air pollution, physical inactivity, obesity, and type 2 diabetes.

Results: Age-adjusted AD mortality rate was significantly increased over time (+27%, p < 0.001). Changes in AD mortality were negatively correlated with trace lithium levels (p = 0.01, r = -0.20), and statistical significance was maintained after controlling for most risk factors except for physical inactivity, obesity, and type 2 diabetes. Furthermore, the prevalence of obesity and type 2 diabetes positively correlated with changes in AD mortality (p = 0.01 and 0.03, respectively), but also negatively correlated with trace lithium in drinking water (p = 0.05 and <0.0001, respectively).

Conclusion: Trace lithium in water is negatively linked with changes in AD mortality, as well as obesity and type 2 diabetes, which are important risk factors for AD.

Keywords: Dementia; GSK3; neuroprotection; obesity; type 2 diabetes.

Fig.1

A) Trace levels of lithium in the Texas public water supply is negatively linked with changes in AD mortality. B) Texas counties below the median level of lithium concentration (0.04 mg/L) have greater increases in AD mortality over time. *p≤0.05 using a Student’s t-test. For (B), values are means±standard error.

Fig.2

Changes in age-adjusted AD mortality are positively associated with the prevalence of obesity (A) and type 2 diabetes (B) and the percent of population that are physically inactive (C).

Fig.3

Trace lithium levels in drinking water is negatively associated with the prevalence of obesity (A) and type 2 diabetes (B).

Fig.4

Trace lithium levels are higher in counties with less than 20 AD deaths compared with counties with more than 20 AD deaths. Counties with less than 20 AD deaths across both time periods were flagged as unreliable in the CDC Wonder Database; counties with more than 20 AD deaths across both time periods were flagged as reliable in the CDC Wonder Database. ***p≤0.001 using a non-parametric Mann-Whitney test to compare ranks. Values are means±standard error.