Alzheimers disease affects forty-five million people and is the fifth leading cause of death in the 65 plus population. There is no complete cure for the disease, currently. However, lithium is being evaluated for its effectiveness as a potential therapeutic measure. One of the leading causes of Alzheimers is the hyperphosphorylation of the tau protein by the enzyme GSK-3, which leads to the overproduction of amyloid peptides that cause cell death. To combat this toxic amyloid aggregation, lithium upregulates the production of neuroprotectors and neurotrophic factors, as well as inhibiting the GSK-3 enzyme. Lithium also stimulates neurogenesis within the hippocampus, making it thicker. Yet another cause of Alzheimer's disease is the dysregulation of calcium ions within the brain. Too much or too little calcium within the brain can lead to cell death. Lithium is able to restore the intracellular calcium homeostasis through inhibiting the wrongful influx of calcium upstream. It also promotes the redirection of the influx of the calcium ions into the lumen of the endoplasmic reticulum of the cells to reduce the oxidative stress within the mitochondria.
In 2009, a study was performed by Hampel and colleagues that asked patients with Alzheimers to take a low dose of lithium daily for three months; it resulted in a significant slowing of cognitive decline, benefitting patients being in the prodromal stage the most. Upon a secondary analysis, the brains of the Alzheimers patients were studied and shown to have an increase in BDNF markers, meaning they had actually shown cognitive improvement. Another study, a population study this time by Kessing et al., showed a negative correlation between Alzheimer's disease deaths and the presence of lithium in drinking water. Areas with increased lithium in their drinking water showed less dementia overall in their population.