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REVIEW article

Front. Neurol.
Sec. Dementia and Neurodegenerative Diseases
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1534193
This article is part of the Research Topic Blood, Cerebrospinal Fluid, and Vascular Biomarkers for Dementia View all 12 articles

Blood-based Biomarkers in Mild Behavioral Impairment: An Updated Overview

Provisionally accepted
Efthalia Angelopoulou Efthalia Angelopoulou 1*Xenia Androni Xenia Androni 1Chiara Villa Chiara Villa 2,3Alexandros Hatzimanolis Alexandros Hatzimanolis 4Nikolaos Scarmeas Nikolaos Scarmeas 1Sokratis G Papageorgiou Sokratis G Papageorgiou 1
  • 1 First Department of Neurology, Aeginition Hospital, National and Kapodistrian University of Athens, Athens, Greece
  • 2 University of Milano-Bicocca, Milan, Italy
  • 3 Department of Medicine and Surgery, University of Milano Bicocca, Monza, Italy
  • 4 First Department of Psychiatry, Aeginition Hospital, National and Kapodistrian University of Athens, Athens, Greece

The final, formatted version of the article will be published soon.

    Identifying individuals at-risk for dementia is one of the critical objectives of current research efforts, highlighting the need for simple, cost-effective, and minimally invasive biomarkers. Mild behavioral impairment (MBI), characterized by the emergence of persistent neuropsychiatric manifestations in older adults, has attracted increasing attention as a potential early indicator of cognitive decline and dementia. A growing number of studies have recently begun to explore the relationship between MBI and several blood-based biomarkers associated with Alzheimer's disease (AD) pathology, neurodegeneration, as well as systemic metabolic and inflammatory dysregulation. In this context, MBI has been associated with lower plasma Aβ42/Αβb40 ratio, higher plasma phosphorylated tau at threonine 181 (p-tau181), increased neurofilament light chain (NfL) levels, as well as disturbances in metabolic markers, including homocysteine, insulin and ferritin, suggesting a multifaceted neurobiological basis for this syndrome. These findings offer insights into the underlying pathophysiology of MBI, and connection between neuropsychiatric symptoms and progression of AD. In this narrative review, we aim to summarize and critically discuss the emerging literature evidence linking MBI to blood-based biomarkers, hoping to shed more light on MBI's pathophysiology, its connection to AD-related neurobiology, as well as its potential practical utility for predicting cognitive impairment, guiding early interventions and managing the risk for dementia.

    Keywords: Efthalia Angelopoulou1, Xenia Androni1, Chiara Villa2, 3, Alexandros Hatzimanolis34, Nikolaos Scarmeas1, Sokratis Papageorgiou1

    Received: 25 Nov 2024; Accepted: 24 Jan 2025.

    Copyright: © 2025 Angelopoulou, Androni, Villa, Hatzimanolis, Scarmeas and Papageorgiou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Efthalia Angelopoulou, First Department of Neurology, Aeginition Hospital, National and Kapodistrian University of Athens, Athens, 10679, Greece

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.