SR电子T1在症状前的脑代谢谱入库单5年随访中的携带者[f] Neurology [j] Neurology [d] L半岛投注体育官网ippincott Williams & Wilkins SP e396 OP e407 DO 10.1212/WNL.0000000000201439签证官100是4 A1达里奥Saracino A1 Leila Sellami A1雨果小旅店的A1马里昂Houot A1梅勒妮Pelegrini-Issac A1 Aurelie Funkiewiez A1菊花里纳尔蒂A1马克西姆A1右路放倒卡罗尔Azuar A1 Valerie Causse-Lemercier A1爱丽丝Jaillard A1佛罗伦萨Pasquier A1马修Chastan A1大卫Wallon A1安妮Hitzel A1杰雷米Pariente A1含有杏仁的Pallardy A1克莱尔Boutoleau-Bretonniere A1 Eric Guedj A1米拉Didic A1 Raffaella阶段A1 Aurelie ka A1 Marie-Odile Habert A1伊莎贝尔Le Ber A1代表背景和目的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