¿Se Podrá Recomendar el Tratamiento con Litio Para el Deterioro Cognitivo Leve y la Demencia por Enfermedad de Alzheimer? Falta Evidencia Sobre su Eficacia y su Seguridad: Revisión Sistemática y Metanálisis

Introduction

Alzheimer's disease is the most prevalent neurodegenerative disease worldwide. Currently available treatments are scarce and have modest effects. Lithium has been shown to decrease cognitive impairment in people with bipolar affective disorder. However, studies evaluating lithium for cognitive impairment in Alzheimer's disease remain controversial.

Methods

We conducted a systematic search of the literature using PubMed, EMBASE, the Cochrane Library, LILACS, and Google Scholar between 30 April and 10 May 2021. Randomised controlled clinical trials (RCTs) conducted to evaluate the efficacy and safety of lithium as a treatment for cognitive impairment in people with dementia and mild cognitive impairment due to Alzheimer's disease were included. The primary outcome was the difference in cognitive functioning at the end of the study. Two authors selected the studies and extracted the data. We calculated the standardised mean differences (SMD) for continuous variables and the relative risk (RR) for dichotomous variables. Review Manager 5.4 software was used for data processing.

Results

2,078 reports were identified and 3 studies with data from 248 participants were included. A fourth report was included for safety analysis. Compared to placebo, no significant difference was found in the cognitive performance of patients with mild cognitive impairment or dementia due to Alzheimer's disease receiving lithium treatment (SMD = –0.39; 95%CI, –0.82 to 0.04; I² = 53%; n = 195). Also, significant differences were not found in the rate of discontinuation for any cause (RR = 0.90; 95%CI, 0.46-1.78; I² = 0%), and the rate of adverse effects between lithium and placebo (RR = 1.29; 95%CI, 0.83-2.03; I² = 0%).

Conclusions

The current evidence is insufficient to assume any effect of lithium as a treatment for cognitive impairment in Alzheimer's disease dementia. It is necessary to continue building better quality studies to justify the use of lithium in this population in clinical practice. Given the toxicity of lithium, adequate pre-selection of patients and close monitoring should be ensured.