Evolving pharmacotherapy in Alzheimer’s disease: from symptomatic management to disease modification-A PRISMA 2020-guided narrative review

Abstract

Alzheimer’s disease (AD) is the leading cause of dementia worldwide and poses an increasing challenge for ageing populations. For decades, pharmacologic management has relied on cholinesterase inhibitors and memantine, which provide modest symptomatic benefit without altering the underlying neurodegenerative process. Recent advances in anti-amyloid monoclonal antibodies and investigational therapies targeting tau pathology, neuroinflammation, and metabolic dysfunction have renewed interest in disease-modifying therapies. This PRISMA 2020-guided narrative review critically evaluates current and emerging pharmacotherapies for AD, with emphasis on clinical efficacy, safety, and relevance to geriatric practice. A structured search of PubMed/MEDLINE, Embase, Scopus, Web of Science, CENTRAL, and ClinicalTrials.gov identified 71,663 records published between January 2000 and January 2026. After screening and eligibility assessment, 18 randomized and phase II/III clinical trials were included in the qualitative synthesis. Owing to substantial heterogeneity in study design, patient populations, and outcome measures, findings were synthesized narratively rather than quantitatively. Cholinesterase inhibitors and memantine were associated with small-to-moderate improvements or stabilization in cognition and global function, although limited durability and tolerability may restrict long-term use. Anti-amyloid monoclonal antibodies, particularly lecanemab and donanemab, demonstrated statistically significant slowing of cognitive decline in early AD; however, the absolute clinical benefits remained modest and were accompanied by amyloid-related imaging abnormalities, necessitating careful monitoring with magnetic resonance imaging. Emerging therapies targeting tau pathology, neuroinflammatory pathways, and metabolic dysfunction remain investigational. Overall, symptomatic therapies continue to represent the foundation of AD management, whereas anti-amyloid monoclonal antibodies mark an important, although incremental, transition toward disease modification in carefully selected patients.