Title:Lithium, a Therapy for AD: Current Evidence from Clinical Trials of Neurodegenerative Disorders
Volume: 13
Issue: 8
Author(s): Orestes V. Forlenza, Ivan Aprahamian, Vanessa J. de Paula and Tomas Hajek
Affiliation:
Keywords:
Lithium and Alzheimer’s disease, lithium and mild cognitive impairment, lithium and amyotrophic lateral sclerosis,
lithium and multiple system atrophy, lithium and neurodegenerative disorders, lithium.
Abstract: Background: Preclinical studies have shown that lithium modifies pathological cascades
implicated in certain neurodegenerative disorders, such as Alzheimer’s disease (AD), Huntigton`s disease
(HD), multiple system atrophy (MSA) and amyotrophic lateral sclerosis (ALS). A critical question
is whether these pharmacodynamic properties of lithium translate into neurodegenerative diseases
modifying effects in human subjects. Methods: We reviewed all English controlled clinical trials published
in PubMed, PsycINFO, Embase, SCOPUS, ISI-Web with the use of lithium for the treatment of neurodegenerative
disorders between July 2004 and July 2014. Results: Lithium showed evidence for positive effects on cognitive functions
and biomarkers in amnestic mild cognitive impairment (aMCI, 1 study) and AD (2 studies), even with doses lower than
those used for mood stabilisation. Studies of Li in HD, MSA and CSI did not show benefits of lithium. However, due to
methodological limitations and small sample size, these studies may be inconclusive. Studies in ALS showed consistently
negative results and presented evidence against the use of lithium for the treatment of this disease. Conclusion: In absence
of disease modifying treatments for any neurodegenerative disorders, the fact that at least 3 studies supported the effect of
lithium in aMCI/AD is noteworthy. Future studies should focus on defining the dose range necessary for neuroprotective
effects to occur.