A study shows that the brains of patients affected by Alzheimer’s disease contain abnormally low quantities of lithium, which suggests that the use of new replacement therapies by this metal could improve the prevention and treatment of this disease.
Lithium carbonate has been used for almost 200 years for the treatment of bipolar disorder, which used to be called manic-depressive disease. This mood disorder, which affects approximately one in 100 people in the world, can transform itself into an incessant cycle of high emotional and lows which, if they are not treated, prevent the normal functioning of individuals and considerably upset the suicide rate (10 to 20 times higher than that of the general population).
This risk is however drastically reduced thanks to lithium treatment. The exact biochemical mechanism responsible for its positive impact on mental processes remains mysterious, but probably involves modulation of ion channels in neurons membranes, allowing the transmission of nerve impulses which is responsible for brain activities.
This metal remains an essential medication for the treatment of many people affected by a mood disorder.
Additional benefits
Several studies carried out over the years suggest that the benefits of lithium would not be restricted to the treatment of bipolar people. For example, it has been observed that the lithium treatment of people affected by a cognitive decline was associated with an improvement in their memory and delayed progression to Alzheimer’s disease(1).
It has also been observed that bipolar people treated with lithium presented a significantly reduced risk (40%) to develop Alzheimer’s disease, a protective effect which is not observed for other drugs used for the treatment of these patients (antiepileptics, antidepressants or antipsychotics)(2).
Lithium deficiency
A recent study of great importance makes it possible to better understand the positive effects of lithium on cognitive processes and the prevention of neurodegenerescences (3). In this study, the researchers measured the concentrations of 27 distinct metals in the prefrontal cortex (a region very affected by Alzheimer’s disease) and the cerebellum (region not affected by the disease and which has served as control).
By comparing the measures made on healthy brains, brains affected by a cognitive decline or by Alzheimer’s disease, they observed that lithium was the only metal that significantly decreased in the prefrontal cortex of brains from sick people, with cognitive decline or Alzheimer’s disease.
Cognitive decline
Using a mouse model predisposed to develop Alzheimer’s disease, researchers have shown that a drastic reduction in the quantity of lithium in the brain (eliminating the metal of animal food) drastically increased the formation of aggregates of beta-amyloid and tau proteins, two types of deposits typically observed in the brain of patients with Alzheimer.
This is accompanied by a strong inflammatory reaction which leads to a loss of interneurons connections (synapses) and an acceleration of the decline of cognitive functions.
Conversely, when animals are treated with a lithium compound which improves its bioavailability (lithium ororate), there is a marked decrease in the appearance of amyloid and tau deposits and preservation of the cognitive functions of animals.
These observations suggest that disturbances in lithium metabolism could represent an early step in the development of cognitive problems leading to Alzheimer’s disease. Correct this impairment using therapies of replacement by lithium could therefore represent a new promising approach in our fight against these incapacitating diseases; This is an important progress in science.
(1) Forlenza OV et coll. Clinical and biological effects of long-term lithium treatment in older adults with amnestic mild cognitive impairment: randomised clinical trial. Br. J. Psychiatry 2019; 215: 668-674.
(2) Kessing LV et coll. Does lithium protect against dementia? Bipolar Disord. 2010; 12: 87-94.
(3) Aron L et coll. Lithium deficiency and the onset of Alzheimer’s disease. Naturepublished on August 6, 2025.
