Emerging Concepts in Diagnosis, Pathologic Features, and Treatment of Limbic-Predominant Amnestic Neurodegenerative Syndrome (LANS): A Narrative Review.

INTRODUCTION: Neurodegenerative disorders (NDs) are characterized by progressive loss of function and destruction of the central and peripheral nervous systems. These disorders result in devastating irreversible cognitive decline and affect millions of people worldwide. Alzheimer's disease (AD) is a common cause of dementia that increases in incidence with increasing age. Limbic-predominant amnestic neurodegenerative syndrome (LANS) is another common etiology of amnestic symptoms and often affects the "oldest-old" of the population. The two disorders share many similarities yet are clearly pathologically distinct. Establishing robust classifications to distinguish these two disorders is key to future management and care of an aging population. The present investigation explored the pathophysiology of neurodegenerative disorders (NDs), specifically Alzheimer's disease (AD), limbic-predominant amnestic neurodegenerative syndrome (LANS), and limbic-predominant age-related TDP-43 encephalopathy (LATE).

METHODS: We performed a comprehensive narrative review of the literature, covering studies from database inception through November 2024. We searched PubMed/MEDLINE, Embase, Web of Science, Cochrane Library, and Google Scholar for relevant publications. We also reviewed reference lists of key articles. Two authors independently screened titles/abstracts for relevance and extracted data on study design, patient population, neuropathologic findings, imaging/biomarker methods, and clinical features. Discrepancies were resolved by discussion. This review synthesized findings on the need for LANS criteria and compared LANS to AD and LATE across clinical, imaging, pathologic, and biomarker domains.

RESULTS: A comprehensive analysis of the key pathologic features and distinctions among selected neurodegenerative syndromes was carried out using peer-reviewed literature.

CONCLUSIONS: Recently proposed clinical criteria for LANS are a milestone in the characterization and further treatment of neurodegenerative disease. Understanding the minute differences in pathophysiology among various NDs allows for pioneering more targeted disease-modifying treatments. This narrative review provides concise reflection between AD and other NDs involving LATE-NC changes.