Abstract
Background: 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).
Methods: 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).
Results: 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.
Conclusions: The results indicate that lithium treatment may have beneficial
effects on cognitive performance in subjects with MCI and AD dementia.
