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Long-term exposure to lithium in drinking water may be protective for dementia

Dr. Joseph Delano Fule Robles
05 Sep 2017

Long-term increased exposure to lithium in drinking water may be associated with a lower incidence of dementia, a recent nationwide, population-based, nested case-control study in Denmark has shown.

In this study where 73,731 patients with dementia and 733,653 controls (median age, 80.3 years; range, 74.984.6 years; 60.7 percent female) were analyzed, the incidence rate ratio (IRR) of dementia was significantly decreased among individuals exposed to more than 15 µg/L compared with 2–5 µg/L of lithium in drinking water (IRR, 0.83 vs 1.22; p<0.001). [JAMA Psychiatry 2017, doi:10.1001/jamapsychiatry.2017.2362]

The pattern was confirmed when the analysis was adjusted for urbanicity (ie, density of population with residence capital or capital suburb as reference) (IRR for 5.1–10.0 μg/L, 1.18; IRR for 10.115.0 μg/L, 1.02; IRR for 15.127.0 μg/L, 0.88).

The same pattern was also observed in patients diagnosed with Alzheimer’s disease (0.78 vs 1.22; p<0.001) or vascular dementia (0.87 vs 1.26; p<0.001), with a significantly lower IRR in the group exposed to more than 15 µg/L compared with 2–5 µg/L of lithium in drinking water.

“This is the first study, to our knowledge, to investigate the association between lithium in drinking water and the incidence of dementia. The study was done during a 28-year exposure period from 1986 to 2013 on drinking water lithium samples from 151 waterworks covering all of Denmark,” the authors pointed out.

“These data are combined with hospital data on incident dementia in an up to 19-year outcome period from 1995 to 2013,” the authors added.

“Our findings are consistent with results of two randomized clinical trials on lithium treatment in dementia, which showed successful outcomes. One trial was on patients with mild cognitive impairment successfully treated with lithium [150–600mg] for 2 years, and another was on patients with Alzheimer’s disease treated with 300 μg of lithium for 15 months,” the authors pointed out. [Br J Psychiatry 2011;198:351-356; Curr Alzheimer Res 2013;10:104-107]

It has been reported that long-term treatment with lithium at low doses can modify the secretion of proinflammatory and anti-inflammatory interleukins in cocultures of cortical and hippocampal neurons with glial cells. [Curr Alzheimer Res 2016;13:848-852]

Long-term treatment with low doses of lithium has also shown effects on cell membrane homeostasis by activating forms of cytosolic phospholipase A2 and calcium-independent phospholipase A2 in primary culture of cortical and hippocampal neurons. [Molecules 2015;20:19878-19885]

There are no brain imaging studies that have reported the effects of microlevels of lithium on brain functioning, but there is evidence of a positive association between lithium treatment and brain gray matter volume. [Curr Alzheimer Res 2016;13:862-872]

Drinking water is a major source of human lithium intake, with groundwater lithium levels in Denmark ranging from 2 μg/L to 30 μg/L. Compared with drinking water in other regions of the world, the lithium levels observed in Danish drinking water are significantly lower. [J Am Coll Nutr 2002;21:14-21]

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