The study is the first to assess the relationship between lithium in drinking water and incidence of dementia. It was conducted in Denmark, where lithium occurs in drinking water mainly due to slow leaching of the chemical from soil and sediment into ground water.
Researchers zeroed in on lithium because it targets multiple biological processes, and may be neuroprotective when used at therapeutic doses, according to animal and human studies quoted in the article. Other studies have suggested that subtherapeutic and even microdoses may have an impact on human cognition. That raised the question whether the amounts of lithium found in drinking water can affect dementia risk.
To investigate the issue, researchers did a nationwide case-control study using Danish-population based registers for 73,731 people aged 50 to 90 years with inpatient and outpatient hospital records listing a diagnosis of dementia between January 1970 and December 2013. Then they matched dementia patients by age and sex to 10 controls without dementia, sampled from the Danish population (n=733 653). Overall, the study population had a median age of 80.3 years, and was 60.7% female and 39.3% male.
Researchers also estimated the mean lithium exposure from water supplying about 42% of the Danish population between 1986-2013, for up to 28 years of exposure.
Analyses included the home addresses of participants, and accounted for changes in residence that could affect exposure to lithium in drinking water. A sensitivity analysis adjusted for urban residence.
. Lithium exposure significantly lower in dementia vs controls vs controls (median, 11.5 μg/L vs 12.2 μg/L. respectively, P < .001)
. Compared to low exposure (2.0 to 5.0 μg/L) higher expsoure showed a nonlinear relationship:
- Significantly lower dementia incidence for > 15.0 μg/L (P < .001)
- Nonsignificantly lower dementia incidence for 10.1 to 15.0 μg/L: (P = .17)
- Significantly higher dementia incidence for 5.1 to 10.0 μg/L (P < .001)
. Nonlinear pattern remained after adjusting for urban residence
-Dementia decreased with urban residence, increased in towns and rural areas
. Similar patterns for Alzheimer disease and vascular dementia
Though the nonlinear relationship may raise questions, the authors mentioned that such relationships are common in medicine. This may reflect activation of one neuroprotective mechanism at lower doses followed by its loss with dosage increases. Another mechanism may take over at higher doses, they hypothesized.
They also mentioned several limitations. The results were not adjusted for several potential confounders, including some factors related to area of residence such as accessibility to healthcare services which may affect the probability of receiving a dementia diagnosis. The study could not account for unknown, long-term changes in lithium in drinking water over the study period, though other studies suggest lithium levels are roughly stable over time.
“Long-term increased exposure to lithium in drinking water may be associated with a lower incidence of dementia in a nonlinear way. However, confounding from other factors associated with municipality of residence cannot be excluded,” first author Lars Vedel Kessing, MD, DMSc of the University of Copenhagen, (Copenhagen, Denmark) and colleagues concluded.
Take Home Points
. Danish study is the first to find that long-term exposure to higher levels of lithium in drinking water may be linked to decreased risk of dementia
. Results showed a nonlinear relationship, with lower risk of dementia at higher levels of exposure, and higher risk at intermediate levels of exposure
. Results cannot exclude confounding from factors related to area of residence
1. Kessing LV, Gerds TA, Knudsen NN, et al. Association of Lithium in Drinking Water With the Incidence of Dementia. JAMA Psychiatry. 2017;74:1005-1010.