Latest Therapeutics in Alzheimer’s Disease: Systematic Review

Abstract

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia globally, with no definitive disease-modifying treatment currently available. Recent therapeutic advances targeting amyloid-beta, tau protein, neuroinflammation, and metabolic pathways reflect a shift in treatment paradigms. However, the comparative efficacy, safety, and translational potential of these emerging strategies remain insufficiently synthesized. Objective: This systematic review aimed to evaluate the latest therapeutic interventions for AD by analyzing randomized clinical trials and pilot studies assessing pharmacologic and non-pharmacologic treatments, with a focus on cognitive outcomes, biomarker changes, and treatment safety. Methods: A systematic review was conducted following PRISMA 2020 guidelines. Databases searched included PubMed, Scopus, Web of Science, and the Cochrane Library, covering publications from December 2018 to August 2023. Studies were included if they were randomized clinical trials involving AD patients aged ≥18 years. Data on interventions, outcomes, and risk of bias were extracted and synthesized narratively. The final sample comprised 21 eligible trials. Ethical compliance with the Declaration of Helsinki was ensured by all primary studies. Statistical outcomes and clinical effects were reported descriptively. Results: Trials included a total of over 7,000 participants. Lecanemab, Donanemab, BI 425809, and masitinib demonstrated statistically significant improvements in cognitive measures (e.g., ADCOMS, ADAS-Cog) and biomarker modulation (e.g., amyloid PET, tau levels). Intranasal insulin and metabolic activators showed functional gains. Safety profiles were generally favorable, though some studies had limited generalizability due to sample size and trial duration. Conclusion: Multiple emerging interventions show promise in modifying the trajectory of Alzheimer’s disease, supporting a move toward personalized and mechanism based treatment approaches. These findings offer valuable clinical insights and highlight the need for integrated, large-scale trials to translate these advances into real-world patient care.