Lithium Cordial To Keep Dementia Away

30. October 2017
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Lithium has been employed for years in the treatment of bipolar disorders and depression. It also has positive effects on dementia disorders. In the face of increasing patient numbers, one psychiatrist has a questionable idea: distributing drinking water containing lithium.

For around for 60 years when dealing with bipolar disorders and severe cases of depressions doctors have turned to lithium salts. “We have repeatedly observed in our patients that lithium is one of the few medications that can eliminate suicidal ideation in the long term”, Professor Dr. Michael Bauer, Director of the Clinic and Polyclinic for Psychiatry and Psychotherapy at Carl Gustav Carus University Hospital in Dresden (Germany), says. Even after such a long time, the medication surprises us with new effects, he adds.

“A certain protective effect against loss of memory and dementia”

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Michael Bauer © Uniklinikum Dresden / Christoph Reichelt

“For example, during the analysis of long-term treatment data we found that lithium also delivered a certain protective effect against memory loss and dementia”, Bauer says. “In a laboratory experiment its neuroprotective effect was quite clearly able to be demonstrated”. The specialist asserts: “If patients take lithium for ten or twenty years, then the dementia rate also drops”.

There are multiple papers to be found on the subject in scientific literature. Researchers at the University of São Paulo, headed by Orestes V. Forlenza, took 45 patients with mild cognitive impairment into a randomised controlled trial. They received either lithium salts up to a target serum concentration of 0.25 to 0.5 mmol/l or a placebo.

After twelve months, the research group ascertained various parameters of all participants. Study leader Forlenza found lower levels of tau protein (p-tau) in the cerebrospinal fluid of subjects who had received lithium. Tau proteins are used as biomarkers for Alzheimer’s disease. At the same time, these persons came off better in the ADASCog-Test cognitive test.

Whereas Forlenza worked with large quantities, Andrade Nunes wanted to know whether much lower doses also have a desirable effect. She worked with patients who were already suffering symptoms of Alzheimer’s dementia. Neurologists had previously diagnosed the disease using the relevant valid guidelines. When the study participant had taken 300 μg lithium per day over 15 months, the condition stabilised.

Healing drinking water

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Lars Vedel Kessing © ResearchGate

This initial work led Lars Vedel Kessing from the University of Copenhagen to an idea. The fluctuation in lithium content in Denmark’s drinking water is relatively large due to differing rock formation in the soil. In the western regions, groundwater contains 0.6 μg/l, whereas levels of up to 30.7 μg/l are reached in the east. Kessing made use of regular patient registers of Scandinavian countries. He had data on 73,731 patients with dementia and 733,653 controls.

The scientist included persons who drank water with only 2.0 to 5.0 μg/l lithium as a dementia comparison group. If the drinking water contained more than 15.0 μg/l, the relative risk (RR) of dementia was 0.83. With concentrations ranging from 10.1 to 15.0 μg/l Kessing ascertained an RR of 0.98. Between 5.1 and 10.0 μg/l the RR was 1.22. All differences were statistically significant.

The results are surprising: the scientist found a linear correlation between dose and effect only in certain areas of concentration range. Kessing cannot explain the phenomenon at present. The question of whether his results are clinically relevant also remains unanswered in his study.

Simple and inexpensive intervention

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John J. McGrath © University of Queensland

Despite these open questions, John J. McGrath of the University of Queensland in the Australian city of Brisbane is pondering practical applications. In one editorial he speculates: “The prospect of relatively safe, simple and inexpensive intervention, ie. the optimisation of lithium concentrations in drinking water, so as to avoid dementia, is tempting”. This is especially relevant in the face of increasing patient numbers and the lack of therapies, he says. “To this extent, any preventive measure is particularly important”, McGrath adds.

He also brings into the discussion other desirable effects from his point of view. More than 25 years ago, researchers had already identified an association of lower suicide and crime rates with water containing higher lithium-concentrations. However, McGrath has not addressed the matter of undesirable side effects.

Serial risks

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Elisabetta Patorno © Brigham and Women’s Hospital

Lithium, depending on concentration, is associated with diverse risks. For a long time side effects such as nausea, diarrhoea, tremor, weight gain and euthyroid gland enlargement have been observed. Associations with heart defects were also found with its therapeutical use on pregnant women in the first trimester, Elisabetta Patorno from Brigham and Women’s Hospital, Harvard Medical School (Boston) reports. The basis for this was a cohort including 1,325,563 pregnant women. Of these 663 had received lithium. The prevalence of heart defects when using pharmacotherapy stood at 2.41 per 100 births (compared to 1.15 out of 100 children).

The relative risk was dose-dependent, which should be considered another proof of an association. Figures provided by Patorno in this respect are: 1.11 (600 mg or less per day), 1.60 (601 to 900 mg) and 3.22 (more than 900 mg). In the case of populations being given doses via drinking water, even slightly increased risks would be important.

Who benefits?

In Germany no one is seriously considering the enrichment of drinking water with lithium. Nonetheless the work done by Kessing and colleagues gives us interesting food for thought. Persons with recognised dementia risk factors might benefit from low-dose lithium salts well before they develop dementia. Whether this works will only be able to be shown by randomised controlled studies.

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Image copyright: William Warby, flickr / Licence: CC BY-SA
Pharmaceutics, Research

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