Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, UK.
Curr Opin Neurol. 2023 Aug 1;36(4):276-282. doi: 10.1097/WCO.0000000000001174. Epub 2023 Jun 23.
Frontotemporal dementia (FTD) is a clinically, pathologically and genetically heterogeneous disorder. Whilst disease modifying therapy trials are mostly focused on the symptomatic phase, future studies will move earlier in the disease aiming to prevent symptom onset. This review summarizes the recent work to better understand this presymptomatic period.
The presymptomatic phase can be split into preclinical and prodromal stages. The onset of the preclinical phase is defined by the first presence of pathological inclusions of tau, TDP-43 or fused in sarcoma in the brain. Definitive biomarkers of these pathologies do not yet exist for FTD. The prodromal phase is defined by the onset of mild symptoms. Recent work has highlighted the wide phenotypic spectrum that occurs, with the concept of mild cognitive ± behavioural ± motor impairment (MCBMI) being put forward, and additions to scales such as the CDR plus NACC FTLD now incorporating neuropsychiatric and motor symptoms.
It will be important to better characterize the presymptomatic period moving forward and develop robust biomarkers that can be used both for stratification and outcome measures in prevention trials. The work of the FTD Prevention Initiative aims to facilitate this by bringing together data from natural history studies across the world.
额颞叶痴呆（FTD）是一种临床表现、病理学和遗传学均存在异质性的疾病。虽然针对疾病修饰疗法的试验主要集中在症状期，但未来的研究将更早地开展，旨在预防症状出现。本综述总结了近期为更好地理解这一无症状期所开展的工作。
无症状期可分为临床前和前驱期。临床前阶段的开始定义为大脑中首次出现 tau、TDP-43 或融合肉瘤的病理性包涵体。目前尚不存在 FTD 这些病理学的明确生物标志物。前驱期的定义是轻度症状的出现。最近的研究强调了广泛的表型谱，提出了轻度认知±行为±运动障碍（MCBMI）的概念，并在 CDR 加 NACC FTD 等量表中增加了神经精神和运动症状。
未来，重要的是更好地描述无症状期，并开发出能够用于预防试验分层和结果测量的可靠生物标志物。FTD 预防倡议的工作旨在通过汇集来自世界各地自然史研究的数据来促进这一目标的实现。
