Harandi Hamid, Mohammadi Soheil, Jahanshahi Ali, Dolatshahi Mahsa, Alikarami Sogol, Zafari Rasa, Raji Cyrus A
School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Research Center for Antibiotic Stewardship and Antimicrobial Resistance, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
J Cachexia Sarcopenia Muscle. 2025 Feb;16(1):e13719. doi: 10.1002/jcsm.13719.
Frailty is a chronic condition characterised by the progressive decline of multiple physiological functions. There is a critical need to investigate neuroimaging findings in nondemented frail individuals to better understand the underlying mechanisms and implications of frailty on brain health. This paper is aimed at reviewing neuroimaging studies assessing brain changes in nondemented frail individuals to understand the neuropsychological basis of frailty.
A systematic review was conducted on studies focusing on neuroimaging modalities in frailty, including MRI, fMRI, DTI and PET. The review was based on PRISMA instructions and a two-step screening process. The studies evaluating neuroimaging findings of nondemented frail individuals, regardless of publication time or participant age, were included. Data were extracted from the included studies, and the quality of the studies as well as risk of bias was assessed.
Out of 1604 studies screened, 22 eligible studies were included. Out of these, 10 studies had good quality, while others had fair quality according to the Newcastle Ottawa scale (NOS). Of these studies, 18 used Fried criteria or a modified version of it to diagnose frailty, while the Edmonton frailty score (EFS), Rockwood and Mitnitski frailty index and frailty index (FI) were implemented by the remaining studies. The MRI findings indicated significant differences in brain structure between nondemented frail and robust individuals, including an increased number and size of white matter hyperintensities, reduced grey matter volume, higher cerebrospinal fluid (CSF) volume and increased number of cerebral microbleeds (CMBs) in frail participants compared to the robust ones. The studies showed no significant difference between at-risk and robust groups regarding total intracranial volume (TIV). The number of CMBs was associated with prefrailty status and its severity. fMRI studies showed decreased intranetwork mean functional connectivity (FC) in nondemented frail individuals. DTI studies showed lower fractional anisotropy (FA), higher axial diffusivity (AD) and higher radial diffusivity (RD) in the nondemented frail group. The PET scan study showed that mean cortical beta-amyloid level was not associated with FI, but the accumulation of beta-amyloid in the anterior and posterior putamen and precuneus region significantly correlated with frailty and its severity.
The study reveals significant differences in brain structures between nondemented frail and robust individuals, including increased white matter hyperintensities and reduced grey matter volume. These differences suggest that vascular changes and brain atrophy in nondemented frail individuals may contribute to cognitive impairment and dementia in the future.
衰弱是一种以多种生理功能逐渐衰退为特征的慢性疾病。迫切需要研究非痴呆衰弱个体的神经影像学表现，以更好地理解衰弱对大脑健康的潜在机制和影响。本文旨在综述评估非痴呆衰弱个体大脑变化的神经影像学研究，以了解衰弱的神经心理学基础。
对聚焦于衰弱的神经影像学模式的研究进行系统综述，包括磁共振成像（MRI）、功能磁共振成像（fMRI）、弥散张量成像（DTI）和正电子发射断层扫描（PET）。该综述基于PRISMA指南和两步筛选过程。纳入评估非痴呆衰弱个体神经影像学表现的研究，无论其发表时间或参与者年龄。从纳入的研究中提取数据，并评估研究质量和偏倚风险。
在筛选的1604项研究中，纳入了22项符合条件的研究。其中，根据纽卡斯尔渥太华量表（NOS），10项研究质量良好，其他研究质量一般。在这些研究中，18项使用Fried标准或其修改版本来诊断衰弱，其余研究采用埃德蒙顿衰弱评分（EFS）、Rockwood和Mitnitski衰弱指数以及衰弱指数（FI）。MRI结果表明，非痴呆衰弱个体与健康个体在脑结构上存在显著差异，包括衰弱参与者的白质高信号数量和大小增加、灰质体积减少、脑脊液（CSF）体积增加以及脑微出血（CMB）数量增加。研究表明，有风险组和健康组在总颅内体积（TIV）方面无显著差异。CMB的数量与衰弱前期状态及其严重程度相关。fMRI研究表明，非痴呆衰弱个体的网络内平均功能连接（FC）降低。DTI研究表明，非痴呆衰弱组的分数各向异性（FA）较低、轴向扩散率（AD）较高和径向扩散率（RD）较高。PET扫描研究表明，平均皮质β-淀粉样蛋白水平与FI无关，但β-淀粉样蛋白在前、后壳核和楔前叶区域的积聚与衰弱及其严重程度显著相关。
该研究揭示了非痴呆衰弱个体与健康个体在脑结构上的显著差异，包括白质高信号增加和灰质体积减少。这些差异表明，非痴呆衰弱个体的血管变化和脑萎缩可能在未来导致认知障碍和痴呆。
