Scientists from McGill University are suggesting a novel microdose formulation of lithium could not only slow the progression of Alzheimer’s disease in its initial stages, but also potentially improve cognition at the early stages of decline. The research builds on decades of study into the links between lithium and dementia.
Lithium is probably best known as a treatment for bipolar disorder, although in the early parts of the 20th century the mineral was widely used as a general brain health tonic. Early formulations of the popular soft drink 7 Up contained lithium until the mineral was banned as a beverage supplement in 1948 due to its frequent toxic side effects.
Despite the known neuroprotective and mood stabilizing benefits of lithium as an essential trace mineral, the problem clinicians have faced in harnessing its therapeutic effects is that it very easily becomes toxic when sustained doses are too high.
Prior human trials into the effects of lithium in Alzheimer’s patients have delivered mixed results. While some studies have found lithium may prevent, or at least slow, progression of the disease, the side effects of sustained high doses make the treatment relatively untenable.
As lithium is naturally found in low levels in many water supplies, a body of epidemiological research has uncovered a correlation between lower rates of dementia in a community and higher levels of lithium in drinking water. This research suggests that very low sustained doses of lithium may be protective against the onset of dementia.
An important study published in 2017 established the efficacy of a new microdose lithium formulation in protecting against the progression of Alzheimer’s disease in a rodent model. That research tested a therapeutic agent called NP03, an encapsulated oral lithium formulation that can bypass degradation by acids in the gastrointestinal track, resulting in high central nervous system uptake. This means significantly lower doses can be administered compared to conventional lithium.
"Microdoses of lithium at concentrations hundreds of times lower than applied in the clinic for mood disorders were administered at early amyloid pathology stages in the Alzheimer's-like transgenic rat,” says Claudio Cuello, senior author on the new study, explaining the results of his team’s earlier research. “These results were remarkably positive and were published in 2017 in Translational Psychiatry and they stimulated us to continue working with this approach on a more advanced pathology.”
This new study explores the effects of the novel lithium formulation on a slightly more advanced stage of Alzheimer’s disease. The experiments investigated the efficacy of NP03 administered at a late preclinical stage of Alzheimer’s pathology, when amyloid protein plaques have begun forming and symptomatic signs of cognitive decline are just beginning. The results impressively demonstrated the novel lithium microdose reduced levels of amyloid plaques, reversed memory deficits, and lowered neuroinflammatory markers in the rodent model.
"From a practical point of view our findings show that microdoses of lithium in formulations such as the one we used, which facilitates passage to the brain through the brain-blood barrier while minimizing levels of lithium in the blood, sparing individuals from adverse effects, should find immediate therapeutic applications," says Cuello. "While it is unlikely that any medication will revert the irreversible brain damage at the clinical stages of Alzheimer's it is very likely that a treatment with microdoses of encapsulated lithium should have tangible beneficial effects at early, preclinical stages of the disease."
As Cuello suggests, the mixed results from prior human clinical trials examining lithium and Alzheimer’s may stem from the irreversible nature of neurodegeneration associated with the disease. It is probable that once severe cognitive decline has occurred it may not be repairable. So the hypothesis is very low doses of lithium may only be effective when administered over sustained periods of time before major symptomatic signs of dementia appear.
This new research points to these potential neuroprotective benefits from sustained lithium microdoses. However, it is important to note this particular microdose formulation is still yet to be tested in human subjects with Alzheimer’s, so much more work is necessary before it can be deployed as a clinical treatment.
The new study was published in the Journal of Alzheimer’s Disease.
Source: McGill University