Journal of Advanced Clinical Neurology Research

Abstract

Cognitive impairment represents one of the most pressing challenges in modern medicine, affecting millions of individuals worldwide and placing substantial burdens on healthcare systems and families. Recent years have witnessed remarkable progress in our understanding of cognitive decline, with significant advances in biomarker development, therapeutic target identification, and clinical trial design. This comprehensive review synthesizes research findings from 2022 to 2024, examining three critical domains: biomarkers for early detection and disease monitoring, therapeutic targets for intervention development, and the current landscape of clinical trials. Our analysis reveals that plasma amyloid-beta 42/40 (Aβ42/40) ratio has emerged as the most clinically relevant blood-based biomarker, offering accessible and cost-effective screening capabilities. The therapeutic landscape has shifted dramatically, with 77% of new treatments now targeting disease-modifying mechanisms rather than merely addressing symptoms. Notably, the first randomized controlled trial demonstrating the efficacy of intensive lifestyle interventions in mild cognitive impairment and early dementia marks a paradigm shift toward multi-domain approaches. Currently, 495 active clinical trials funded by the National Institute on Aging are investigating diverse interventions, from anti-amyloid therapies like BIIB080 to comprehensive lifestyle modifications. The integration of accessible biomarkers, evidence-based lifestyle interventions, and disease-modifying pharmacological treatments offers unprecedented opportunities for preventing or slowing cognitive decline. This review highlights the convergence of precision medicine approaches, multi-domain interventions, and biomarker-guided treatment selection as the future of cognitive impairment management.