Association of Lithium in Drinking Water With the Incidence of Dementia

Title	Association of Lithium in Drinking Water With the Incidence of Dementia
Authors	Lars Vedel Kessing, Thomas Alexander Gerds, Nikoline Nygård Knudsen, Lisbeth Flindt Jørgensen, Søren Munch Kristiansen, Denitza Voutchkova, Vibeke Ernstsen, Jörg Schullehner, Birgitte Hansen, Per Kragh Andersen and Annette Kjær Ersbøll
Magazine	JAMA Psychiatry
Date	10/01/2017
DOI	10.1001/jamapsychiatry.2017.2362
Introduction	This case-control study aimed to assess whether the incidence of dementia in the general population relates to long-term exposure to microlevels of lithium present in drinking water. Existing animal and human investigations suggest that lithium, at therapeutic concentrations, can enhance learning and memory, potentially modifying the risk of developing dementia. Furthermore, preliminary studies indicate that subtherapeutic lithium levels, including microlevels, might impact human cognition. The study utilised a Danish nationwide, population-based, nested case-control design. It involved analysing longitudinal, individual geographic data concerning municipality of residence, combined with drinking water measurements and time-specific health records. Participants included all patients aged 50 to 90 years with a hospital diagnosis of dementia between 01/01/1970 and 31/12/2013, along with 10 age- and sex-matched control individuals from the Danish population. The mean lithium exposure in drinking water since 1986 was estimated for all study participants. Data analysis was conducted from 01/01/1995 through 31/12/2013. The primary outcome measured was a diagnosis of dementia from a hospital inpatient or outpatient contact. Secondary outcome measures included diagnoses of Alzheimer’s disease and vascular dementia. The initial analyses compared the distribution of lithium exposure between patients diagnosed with dementia and control individuals. The study enrolled a total of 73,731 patients with dementia and 733,653 controls, with a median age of 80.3 years. A statistically significant difference in lithium exposure was observed between dementia patients (median, 11.5 µg/L) and controls (median, 12.2 µg/L; P < .001). A nonlinear association was evident. Compared to individuals exposed to 2.0 to 5.0 µg/L, the incidence rate ratio (IRR) for dementia decreased in those exposed to more than 15.0 µg/L (IRR, 0.83; 95% CI, 0.81-0.85; P < .001) and was 0.98 for 10.1 to 15.0 µg/L (P = .17). Conversely, the IRR increased for those exposed to 5.1 to 10.0 µg/L (IRR, 1.22; 95% CI, 1.19-1.25; P < .001). Similar patterns were noted when considering Alzheimer’s disease and vascular dementia as outcomes. In conclusion, long-term elevated lithium exposure in drinking water may correlate with a lower incidence of dementia in a nonlinear fashion. However, it is important to acknowledge that confounding variables associated with the municipality of residence cannot be entirely ruled out.
Quote	Lars Vedel Kessing, Thomas Alexander Gerds and Nikoline Nygård Knudsen et al. Association of Lithium in Drinking Water With the Incidence of Dementia. JAMA Psychiatry. 2017. Vol. 74(10):1005. DOI: 10.1001/jamapsychiatry.2017.2362
Element	Lithium (Li)
Industry	Pharmaceutical Industry , Research & Laboratory