Lithium has long been questioned in therapy for Alzheimer’s disease. This is due to the information being gathered isn’t fully convincing because it’s from a multitude of approaches, conditions, and formulations making the results difficult to compare. 

Not Only Adverse Effects

High dosages of lithium cause a number of serious adverse effects which make this approach impracticable for long-term treatments, particularly for the elderly.

A team of researchers at McGill University led by Dr. Claudio Cuello of the Department of Pharmacology and Therapeutics, has shown that, when given in a formulation that facilitates passage to the brain, lithium in doses up to 400 times lower than what is currently being prescribed for mood disorders is capable of both halting signs of advanced Alzheimer’s pathology such as amyloid plaques and of recovering lost cognitive abilities. 

Further Research

Conventional lithium formulation was applied in rats at a dosage similar to that used in clinical practice for mood disorders. The results of the initial tentative studies with conventional lithium formulations and dosage were disappointing however, as the rats rapidly displayed a number of adverse effects. The research avenue was interrupted but renewed when an encapsulated lithium formulation was identified that was reported to have some beneficial effects in a Huntington disease mouse model.

Lithium in doses up to 400 times lower than what is commonly recommended for mood disorders can stop signs of advanced Alzheimer’s disease, such as amyloid plaques and recover lost cognitive abilities.

Findings in Studies

A new lithium formulation was introduced to a rat transgenic model expressing Alzheimer’s-causing human proteins, an animal model they had developed and characterized. This rat exhibited symptoms of Alzheimer’s disease, including gradual accumulation of amyloid plaques in the brain and cognitive deficits at the same time.

Early stages of amyloid pathology in the Alzheimer’s transgenic rat, microdoses of lithium at concentrations hundreds of times smaller than those prescribed in the clinic for mood disorders were administered.

The researchers, inspired by these earlier findings, set out to apply the same formulation of lithium to their transgenic rat models of neuropathological aspects of Alzheimer’s disease at later stages of the disease. This study found that positive effects can also be obtained at more advanced stages in decreasing pathology and increasing cognition, close to late preclinical stages of the disease, when amyloid plaques are already present in the brain and when cognition begins to decrease.

Lithium microdoses in formulations allow passage through the brain-blood barrier to the brain, thus reducing blood lithium levels. It is doubtful that any drug at the clinical stages of Alzheimer’s can reverse the irreversible brain damage, it is very possible that therapy with encapsulated lithium microdoses should have significant beneficial effects at the early preclinical stages of the disease.

Where To Go From Here

There are two different ways to build further on these most recent findings. The first involves investigating combination therapies using lithium formulation in combination with other interesting drug candidates. 

Also, launching clinical trials of this formulation with populations with detectable preclinical Alzheimer’s pathology or with populations genetically predisposed to Alzheimer’s, such as adult individuals with Down Syndrome. Providing a glimmer of hope for an effective treatment for those suffering from Alzheimer’s disease.

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