Laboratory of Epidemiology, Neuroimaging and Telemedicine (LENITEM), Istituto Centro San Giovanni di Dio, Fatebenefratelli, via Pilastroni 4, 25125 Brescia, Italy.
University Department of Psychiatry, Warneford Hospital, Warneford Lane, Oxford OX3 7JX, UK.
Nat Rev Neurol. 2014 Nov;10(11):620-33. doi: 10.1038/nrneurol.2014.178. Epub 2014 Oct 7.
Functional and structural connectivity measures, as assessed by means of functional and diffusion MRI, are emerging as potential intermediate biomarkers for Alzheimer disease (AD) and other disorders. This Review aims to summarize current evidence that connectivity biomarkers are associated with upstream and downstream disease processes (molecular pathology and clinical symptoms, respectively) in the major neurodegenerative diseases. The vast majority of studies have addressed functional and structural connectivity correlates of clinical phenotypes, confirming the predictable correlation with topography and disease severity in AD and frontotemporal dementia. In neurodegenerative diseases with motor symptoms, structural--but, to date, not functional--connectivity has been consistently found to be associated with clinical phenotype and disease severity. In the latest studies, the focus has moved towards the investigation of connectivity correlates of molecular pathology. Studies in cognitively healthy individuals with brain amyloidosis or genetic risk factors for AD have shown functional connectivity abnormalities in preclinical disease stages that are reminiscent of abnormalities observed in symptomatic AD. This shift in approach is promising, and may aid identification of early disease markers, establish a paradigm for other neurodegenerative disorders, shed light on the molecular neurobiology of connectivity disruption and, ultimately, clarify the pathophysiology of neurodegenerative diseases.
功能和结构连接测量，通过功能磁共振成像和弥散张量成像评估，正在成为阿尔茨海默病（AD）和其他疾病的潜在中间生物标志物。这篇综述旨在总结目前的证据，即连接生物标志物与主要神经退行性疾病中的上游和下游疾病过程（分别为分子病理学和临床症状）相关。绝大多数研究都探讨了功能和结构连接与临床表型的相关性，证实了 AD 和额颞叶痴呆中与拓扑结构和疾病严重程度的可预测相关性。在有运动症状的神经退行性疾病中，结构连接（但迄今为止不是功能连接）一直与临床表型和疾病严重程度相关。在最新的研究中，研究重点已经转移到对分子病理学的连接相关性的研究。在有脑淀粉样蛋白或 AD 遗传风险因素的认知健康个体中进行的研究表明，在临床前疾病阶段存在功能连接异常，这些异常类似于在有症状的 AD 中观察到的异常。这种方法的转变很有希望，可能有助于识别早期疾病标志物，为其他神经退行性疾病建立范例，阐明连接破坏的分子神经生物学，并最终阐明神经退行性疾病的病理生理学。
