Neuroprotective effects of lithium: what are the implications in humans with neurodegenerative disorders?

Lithium is used as a first line treatment in bipolar disorder. The neuroprotective effects of lithium in this indication tend to be well known and are mediated by its action on two enzymes: glycogen synthase kinase-3 and inositol monophosphatase-1. Preclinical and clinical studies seek to evaluate the neuroprotective effect of lithium in neurodegenerative disorders. The aims of this literature review is to gather clinical studies that investigated the efficacy of lithium in neurodegenerative diseases, using a systematic method based on PubMed data. Results were found concerning Alzheimer's disease and related dementias, Huntington's disease, amyotrophic lateral sclerosis and spino-cerebellar ataxia. Lithium exposure showed a potential neuroprotective effect in studies on psychiatric populations with a lower prevalence of Alzheimer's disease in exposed patients. In patients with mild cognitive impairment, lithium would be associated with clinical improvement and a lower level of cerebrospinal phosphorylated tau protein. Lithium would allow at least a partial improvement in symptoms, including suicidal thoughts, in Huntington's disease. Despite several positive case reports and short studies, further controlled researches have failed to substantiate any positive effects of lithium exposure in amyotrophic lateral sclerosis. In spinocerebellar ataxia, introduction of lithium may be of benefits in terms of improvement of cerebellar symptoms. Large randomized controlled trials are required to asses the effect of early exposure lithium in these indications, based on reliable biological markers of disease.