Supplementary file 2_Risk factors of mild behavioral impairment: a systematic review.docx

IntroductionMild Behavioral Impairment (MBI) represents a predementia syndrome marked by neuropsychiatric symptoms that may precede detectable cognitive decline. Identifying factors associated with MBI is critical for developing targeted prevention strategies in neurodegenerative disorders.
MethodsThis systematic review adhered to PRISMA 2020 guidelines, searching PubMed, Scopus, Web of Science, ScienceDirect, and Embase through May 2024. Forty-one human studies meeting predefined inclusion criteria were selected through dual independent screening.
ResultsFive key domains emerged: (1) Genetic susceptibility (APOE ε4 allele showing strongest association), (2) Motor system pathology (particularly Parkinsonian features), (3) Multisensory deficits (auditory impairment demonstrating bidirectional relationships), (4) Metabolic dysregulation (diabetes mellitus and frailty phenotypes), and (5) Neuroanatomical correlates (frontolimbic atrophy patterns on MRI). The interaction between genetic predisposition and environmental/lifestyle factors appears central to MBI pathogenesis.
ConclusionMBI manifests as a multidimensional interface between molecular mechanisms and clinical phenomenology. Our synthesis supports the implementation of transdiagnostic screening protocols integrating behavioral biomarkers with conventional cognitive assessments. Future research should prioritize longitudinal designs to establish causal pathways and intervention thresholds.

引言 轻度行为障碍（Mild Behavioral Impairment, MBI）是一种痴呆前综合征，以早于可检测到的认知衰退出现的神经精神症状为特征。明确与MBI相关的影响因素，对于神经退行性疾病的靶向预防策略开发至关重要。
方法 本系统综述遵循PRISMA 2020报告指南，检索了截至2024年5月的PubMed、Scopus、Web of Science、ScienceDirect及Embase数据库。通过双人独立筛选流程，最终纳入41项符合预先设定纳入标准的人体研究。
结果 研究共归纳出五大核心领域：（1）遗传易感性（载脂蛋白E ε4等位基因（APOE ε4）与MBI的关联最为显著）；（2）运动系统病理改变（尤其是帕金森样特征）；（3）多感觉功能缺陷（听觉损害与MBI存在双向关联）；（4）代谢紊乱（包括糖尿病及衰弱表型）；（5）神经解剖学相关特征（磁共振成像（Magnetic Resonance Imaging, MRI）可见额边缘系统萎缩模式）。遗传易感性与环境/生活方式因素之间的相互作用，似乎是MBI发病机制的核心环节。
结论 MBI是分子机制与临床表型之间的多维度交叉界面。本综述的综合分析结果支持采用整合行为生物标志物与传统认知评估的跨诊断筛查方案。未来研究应优先开展纵向设计研究，以明确MBI的致病通路及干预阈值。