Lateral Temporal Lobe: An Early Imaging Marker of the Presymptomatic GRN Disease?
Lateral Temporal Lobe: An Early Imaging Marker of the Presymptomatic GRN Disease?
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DOI：
10.3233/jad-150270
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
Predict-PGRN study group
中科院分区：
文献类型：
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作者：
Caroppo P;Habert MO;Durrleman S;Funkiewiez A;Perlbarg V;Hahn V;Bertin H;Gaubert M;Routier A;Hannequin D;Deramecourt V;Pasquier F;Rivaud-Pechoux S;Vercelletto M;Edouart G;Valabregue R;Lejeune P;Didic M;Corvol JC;Benali H;Lehericy S;Dubois B;Colliot O;Brice A;Le Ber I;Predict-PGRN study group
额颞叶变性（FTLD）的临床前阶段尚未得到很好的表征。我们进行了脑代谢 (FDG-PET) 和结构（皮质厚度）研究，以检测无症状 GRN 突变携带者 (aGRN+) 的早期变化，并在 20 个月的时间内进行纵向评估。基线时，aGRN+ 存在左侧颞叶代谢低下，但没有任何结构变化。重要的是，这是第一个纵向研究，随着时间的推移，aGRN+ 的外侧颞叶和额叶区域的新陈代谢下降得更快。纵向研究中观察到的主要结构变化是携带者左侧颞叶皮质厚度的减少。这项研究的一个限制是样本相对较小（n = 16）；尽管如此，它还是提供了重要的成果。首先，它证明病理过程在临床发病前很长一段时间就已经发生，并且早期神经影像学变化可能在疾病临床发病前大约 20 年被检测到。其次，它表明代谢变化在结构改变和认知缺陷之前是可以检测到的。第三，基线和纵向研究提供了一致的结果，表明外侧颞叶早期参与 GRN 疾病。最后，我们的研究表明，结构和代谢变化可以代表可能的生物标志物，用于监测症状前阶段到临床发病的疾病进展。
The preclinical stage of frontotemporal lobar degeneration (FTLD) is not well characterized. We conducted a brain metabolism (FDG-PET) and structural (cortical thickness) study to detect early changes in asymptomatic GRN mutation carriers (aGRN+) that were evaluated longitudinally over a 20-month period. At baseline, a left lateral temporal lobe hypometabolism was present in aGRN+ without any structural changes. Importantly, this is the first longitudinal study and, across time, the metabolism more rapidly decreased in aGRN+ in lateral temporal and frontal regions. The main structural change observed in the longitudinal study was a reduction of cortical thickness in the left lateral temporal lobe in carriers. A limit of this study is the relatively small sample (n = 16); nevertheless, it provides important results. First, it evidences that the pathological processes develop a long time before clinical onset, and that early neuroimaging changes might be detected approximately 20 years before the clinical onset of disease. Second, it suggests that metabolic changes are detectable before structural modifications and cognitive deficits. Third, both the baseline and longitudinal studies provide converging results implicating lateral temporal lobe as early involved in GRN disease. Finally, our study demonstrates that structural and metabolic changes could represent possible biomarkers to monitor the progression of disease in the presymptomatic stage toward clinical onset.