¹Centro Hospital e Universitário de Coimbra, Psychiatry, Coimbra, Portugal

Background: Mild Cognitive Impairment (MCI) is characterized by cognitive decline exceeding that expected for age, without marked impairment in daily functioning. MCI is often considered a prodromal stage of dementia, highlighting the importance of early interventions to prevent or delay progression to cognitive disorders. Emerging evidence suggests that lithium may have a potential role in the treatment and prevention of neurocognitive decline, supporting further investigation in this population.

Aims & Objectives: This review aims to understand the impact of lithium on mild cognitive impairment.

Method: We conducted a non-systematic literature review, searching PubMed databases, using the keywords “mild cognitive impairment”; “lithium”; "neuroprotective" and “aged”.

Results: Studies suggest that individuals with mild cognitive impairment (MCI) and Alzheimer's disease may have reduced brain lithium levels, potentially affecting pathways involved in amyloid accumulation and microglial gene expression, including ApoE. Preclinical evidence indicates that lithium may help preserve cognitive functions, reduce neuroinflammation, and decrease beta-amyloid formation. Furthermore, several clinical trials have reported that lithium supplementation in individuals with MCI is associated with better long-term cognitive outcomes, as measured by Mini-Mental State Examination (MMSE), compared to control groups. Dysregulation of glycogen synthase kinase-3 (GSK-3) has been implicated in Alzheimer's disease and neuroinflammatory processes, and its inhibition has been shown to reduce the severity of neurocognitive disorders. Lithium is a potent GSK-3 inhibitor that may exert neuroprotective effects by reducing neurofibrillary tangles. Clinical trials indicate that lithium is generally well-tolerated, with few adverse effects, highlighting the importance of regular monitoring in clinical practice. Currently, we are awaiting the results of the LATTICE study, which began in 2017. This randomized controlled trial followed individuals with mild cognitive impairment receiving lithium for two years, with the primary aim of evaluating its neuroprotective potential.

Discussion & Conclusions: Lithium appears promising as a neuroprotective agent. Preventing or delaying cognitive decline is crucial due to its significant impact on patients and caregivers. Further research is required to assess lithium’s efficacy, safety, and potential adverse effects.