Clinical Effectiveness of Treatments for Mild Cognitive Impairment in Adults: A Systematic Review

Background/Objectives: Mild cognitive impairment (MCI) represents an intermediate stage between normal ageing and dementia, with a high annual progression rate. Despite its clinical relevance, no pharmacological treatment has been definitively approved for this condition; however, multiple pharmacological and non-pharmacological strategies have been investigated for their potential benefits. This systematic review assessed the effectiveness of both types of interventions in adults with MCI, aiming to identify effective strategies to preserve cognitive function. Methods: A systematic search (2017-2025) was conducted in PubMed, Scopus, ScienceDirect, SpringerLink, and WOS, following PRISMA guidelines. Randomised controlled trials and quasi-experimental studies involving adults aged ≥ 50 years with a diagnosis of MCI were included. Outcomes were evaluated in terms of cognitive, functional, behavioural, and quality-of-life improvements. Risk of bias was assessed using the RoB 2 and ROBINS-I tools. Results: Of 108,700 records screened, 40 studies were included. Non-pharmacological interventions, such as cognitive training (conventional, computerised, or virtual reality-based), consistently improved memory, attention, and executive functions (e.g., MoCA: +3.84 points; p < 0.001). Transcranial magnetic stimulation combined with physical exercise also demonstrated significant benefits (p = 0.025). Among pharmacological treatments, only vortioxetine and choline alfoscerate showed modest improvements; cholinesterase inhibitors had limited effects and frequent adverse events. Complementary therapies (yoga, probiotics, and acupuncture) yielded promising outcomes but require further validation. Conclusions: Non-pharmacological strategies, particularly cognitive training and physical exercise, emerge as the most effective and safe approaches for managing MCI. The inclusion of pharmacological interventions with preliminary evidence of benefit should be considered within a personalised, multimodal approach, while recognising the current absence of approved drug treatments for MCI. Further research is needed in underrepresented populations, such as those in Latin America.