Department of Neurology, Alzheimer Center, Erasmus MC University Medical Center, Dr. Molewaterplein 40, 3000 CA, Rotterdam, The Netherlands.
Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
J Neurol. 2020 Jun;267(6):1603-1612. doi: 10.1007/s00415-020-09738-y. Epub 2020 Feb 12.
Trials to test disease-modifying treatments for frontotemporal dementia are eagerly awaited and sensitive instruments to assess potential treatment effects are increasingly urgent, yet lacking thus far. We aimed to identify gene-specific instruments assessing clinical onset and disease progression by comparing cognitive functioning between bvFTD patients across genetic mutations.
We examined differences in 7 cognitive domains between bvFTD patients with GRN (n = 20), MAPT (n = 29) or C9orf72 (n = 31) mutations, and non-carriers (n = 24), and described longitudinal (M = 22.6 months, SD = 16.6) data in a subsample (n = 27).
Patients showed overall cognitive impairment, except memory recall, working memory and visuoconstruction. GRN patients performed lower on executive function (mean difference - 2.1; 95%CI - 4.1 to - 0.5) compared to MAPT and lower on attention compared to MAPT (mean difference - 2.5; 95%CI - 4.7 to - 0.3) and C9orf72 (mean difference - 2.4; 95%CI - 4.5 to - 0.3). Only MAPT patients were impaired on delayed recall (mean difference - 1.4; 95%CI - 2.1 to - 0.7). GRN patients declined rapidly on attention and memory, MAPT declined in confrontation naming, whereas C9orf72 patients were globally impaired but remained relatively stable over time on all cognitive domains.
This study shows gene-specific cognitive profiles in bvFTD, which underlines the value of neuropsychological tests as outcome measures in upcoming trials for genetic bvFTD.
人们急切地期待着针对额颞叶痴呆的疾病修饰治疗试验，并且越来越迫切地需要敏感的工具来评估潜在的治疗效果，但迄今为止这方面的工具仍很缺乏。我们旨在通过比较不同基因突变的额颞叶痴呆患者的认知功能，确定针对特定基因的评估疾病临床发作和进展的工具。
我们比较了 GRN（n=20）、MAPT（n=29）或 C9orf72（n=31）突变的额颞叶痴呆患者与非携带者（n=24）之间 7 个认知领域的差异，并在亚样本（n=27）中描述了纵向（M=22.6 个月，SD=16.6）数据。
患者表现出全面的认知障碍，除了记忆回忆、工作记忆和视觉构建。与 MAPT 和 C9orf72 相比，GRN 患者的执行功能（平均差异-2.1；95%置信区间-4.1 至-0.5）较低，注意力（平均差异-2.5；95%置信区间-4.7 至-0.3）也较低。只有 MAPT 患者在延迟回忆（平均差异-1.4；95%置信区间-2.1 至-0.7）方面受损。GRN 患者在注意力和记忆方面迅速下降，MAPT 患者在面对面命名方面下降，而 C9orf72 患者则全面受损，但在所有认知领域的时间推移上保持相对稳定。
本研究显示了额颞叶痴呆中的基因特异性认知特征，这突显了神经心理学测试作为遗传型额颞叶痴呆即将到来的试验中的结局测量的价值。
