Lithium and Alzheimer’s Disease: Experimental, Epidemiological, and Clinical Findings

Abstract

Alzheimer’s disease (AD) represents one of the greatest health-care challenges of the twenty-first century. Besides known pathologies such as intracellular accumulation of neurofibrillary tangles and extracellular deposition of amyloid-beta plaques, other factors, such as dysregulated GSK-3 activity, mitochondrial dysfunction, inflammation, and oxidative stress, have been shown to play a role in the pathogenesis of AD. Over the last two decades, the evidence accumulated for a neuroprotective effect of lithium, as an important mechanism of this ion in mood disorders, reflected by an increase in cerebral gray matter volume in lithium-treated subjects. Neurobiological mechanisms of lithium neuroprotective actions may also be relevant to the pathogenesis and treatment of AD, and they will be delineated. In most epidemiological studies, a negative association between lithium use and dementia has been shown, including two most recent papers regarding a concentration of lithium in drinking water. In this article, the results of initial studies using lithium in the treatment of dementia and showing some promise will also be presented. Therefore, considering the current paucity of treatments for the AD, further testing of lithium as a disease-modifying treatment in this illness may be warranted.