In Lancet Psychiatry (available on line 9 June 2025), Post RM, Li VW, Berk M, and Yatham LN make the case that Lithium should be considered as a disease-modifying drug (DMD) for bipolar disorder. As such, it should be started earlier and used more often to make the course of bipolar disorder more benign, protect cognition, decrease the diagnosis of dementia in old age, decrease the incidence of all-cause mortality, and increase longevity.

In August, 2025 new data have also emerged about lithium having unequivocal anti-Alzheimer’s effects (Aron, L., Ngian, Z.K., Qiu, C. et al. Lithium deficiency and the onset of Alzheimer’s disease. (Nature (2025). https://doi.org/10.1038/s41586-025-09335-x). Patients with bipolar disorder, mild cognitive impairment (MCI), and Alzheimer’s dementia have a deficiency of lithium in their brain but not in the plasma. They created an animal model of dementia by decreasing the amount of lithium in the animal’s food and reproduced all of the memory deficits seen in Alzheimer’s dementia. When animals were treated with low dose lithium, this did not occur. When lithium-deficient animals were treated with lithium their cognition and neurobiological insults in the brain were reversed.

They found that lithium bioavailability was reduced as lithium was sequestered in the amyloid plaques in the brain. However, they found that lithium orotate (LiO) did not bind to the plaques and was more effective than other forms of lithium in reversing the cognitive and neurobiological deficits (including the pathological increases in GSK3B, pro-inflammatory microglial activation, and the loss of synapses, axons and myelin) of the lithium deficient animals. In humans, low dose Li carbonate protects against cognitive decline in MCI (Florenza et al 2011; 2018) compared to placebo in studies of one and two years duration, and micro doses slowed Alzheimer’s disease progression (Nunes et al).

This raises the issue of whether LiO would be more effective than Li in preventing or reversing cognitive decline. The question of what doses of LiO would be most effective for MCI and Alzheimer’s disease also remains to be further studied.

Before these new data emerged, lithium at clinical doses appeared to be a DMD for bipolar disorder, indicating its greater and earlier use was warranted. Now it appears that even low doses of lithium (especially the orotate version) could prevent and possibly reverse some of the cognitive deficits in MCI and Alzheimer’s disease.

THE ENTIRE WORLD VIEW OF THE USE OF LITHIUM IN BOTH BIPOLAR DISORDER AND COGNITIVE DECLINE NOW NEEDS TO BE RE-EVALUATED AND ITS DEFICIT OF USE IN BOTH DISORDERS REVERSED.

‍