TY - JOUR T1 -症状前GRN携带者5年随访期间的脑代谢谱[j] - Neurology - JO - Neurology SP - e396 LP - e407 DO - 10.1212/WNL.0半岛投注体育官网000000000201439六世- 100 - 4 AU -达里奥Saracino盟莱拉Sellami AU -雨果小旅店的非盟-马里昂Houot盟梅兰妮Pelegrini-Issac盟Aurelie Funkiewiez盟马克西姆-菊花里纳尔蒂盟盟右路放倒,卡罗尔Azuar AU -瓦莱丽Causse-Lemercier盟-爱丽丝Jaillard AU -佛罗伦萨Pasquier AU -马蒂厄Chastan盟-大卫Wallon AU -安妮Hitzel AU -杰雷米Pariente盟含有杏仁的Pallardy AU -克莱尔Boutoleau-Bretonniere盟Eric Guedj AU -米拉Didic盟Raffaella阶段非盟- Aurelie ka盟背景和目的GRN变异是家族性额颞叶痴呆(FTD)的常见原因。半岛投注体育官网监测无症状基因变异携带者的疾病进展是在临床发病前提供预防性治疗的主要挑战。本研究旨在评估氟脱氧葡萄糖(FDG) -PET在识别症状前GRN携带者(PS-GRN+)代谢变化并追踪其纵向进展方面的有用性。方法在一项以GRN疾病为重点的前瞻性队列研究(Predict-PGRN)中，对参与者进行为期5年的纵向评估。他们接受了认知/行为评估、血浆神经丝测量、脑MRI和FDG-PET。在每个时间点对两组之间的结构和代谢成像数据进行体素比较。纵向PET变化通过体素比较和代谢百分比年变化法进行评估。分析脑区域代谢与血浆神经丝和认知变化的关系。结果在80名受试者中，58人(27名PS-GRN+和31名非携带者)被纳入分析。 Cross-sectional comparisons between PS-GRN+ and controls found a significant hypometabolism in the left superior temporal sulcus (STS) region (encompassing the middle and superior temporal gyri), approximately 15 years before the expected disease onset, without significant cortical atrophy. The longitudinal metabolic decline over the following 5 years peaked around the right STS in carriers (p < 0.001), without significantly greater volume loss compared with that in controls. Their estimated annualized metabolic decrease (−1.37%) was higher than that in controls (−0.21%, p = 0.004). Lower glucose uptake was associated with higher neurofilament increase (p = 0.003) and lower frontal cognitive scores (p = 0.014) in PS-GRN+.Discussion This study detected brain metabolic changes in the STS region, preceding structural and cognitive alterations, thus contributing to the characterization of the pathochronology of preclinical GRN disease. Owing to the STS involvement in the perception of facially communicated cues, it is likely that its dysfunction contributes to social cognition deficits characterizing FTD. Overall, our study highlights brain metabolic changes as an early disease-tracking biomarker and proposes annualized percent decrease as a metric to monitor therapeutic response in forthcoming trials.AD=Alzheimer disease; ASL=arterial spin labeling; bvFTD=behavioral variant of FTD; CATI=Centre d'Acquisition et de Traitement d'Images; CDR+NACC FTLD=Clinical Dementia Rating scale plus National Alzheimer's Coordinating Center Frontotemporal Lobar Degeneration; EYO=expected years to onset; FDG=fluorodeoxyglucose; FDR=false discovery rate; FTD=frontotemporal dementia; FWHM=full width at half maximum; GMA=gray matter atrophy; HC=healthy control; LMM=linear mixed model; MDRS=Mattis dementia rating scale; MNI=Montreal Neurological Institute; NfL=neurofilament light chain; PAC=percent annual change; PPA=primary progressive aphasia; PS-GRN+=presymptomatic GRN carrier; ROI=region of interest; SPM=statistical parametric mapping; STS=superior temporal sulcus; VBM=voxel-based morphometry ER -