Lithium as a Treatment for Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Abstract

This is the first meta-analysis of randomized placebo-controlled trials testing lithium as a treatment for patients with Alzheimer's disease (AD) and individuals with mild cognitive impairment (MCI). The primary outcome measure was efficacy on cognitive performance as measured through the Alzheimer's Disease Assessment Scale cognitive subscale or the Mini-Mental State Examination. Other outcome measures were drug discontinuation rate, individual side effects, and biological markers (phosphorylated tau 181, total tau, and amyloid-β42) in cerebrospinal fluid (CSF). Three clinical trials including 232 participants that met the study's inclusion criteria were identified. Lithium significantly decreased cognitive decline as compared to placebo (standardized mean difference = -0.41, 95% confidence interval = -0.81 to -0.02, p = 0.04, I2 = 47% , 3 studies, n = 199). There were no significant differences in the rate of attrition, discontinuation due to all causes or adverse events, or CSF biomarkers between treatment groups. The results indicate that lithium treatment may have beneficial effects on cognitive performance in subjects with MCI and AD dementia.