From the Departments of Neurology (J.M.P., L.C.J., J.L.P., E.G.D., L.D.K., L.H.M., J.C.v.S.), Epidemiology (T.d.H.), and Clinical Genetics (R.v.M.), Erasmus Medical Center, Rotterdam; Departments of Radiology (L.C.J., J.L.P., E.G.D., S.A.R.B.R.) and Clinical Genetics (L.D.K.), Leiden University Medical Center; Alzheimer Center and Department of Neurology (E.G.D., Y.A.L.P.) and Department of Clinical Genetics (J.C.v.S.), VU Medical Center, Amsterdam; Department of Neurology (T.d.H.), Sint Franciscus Gasthuis, Rotterdam; and Department of Radiology (S.A.R.B.R.) and Leiden Institute for Brain and Cognition (S.A.R.B.R.), Leiden University, the Netherlands.
Neurology. 2017 Sep 19;89(12):1256-1264. doi: 10.1212/WNL.0000000000004393. Epub 2017 Aug 30.
To investigate cognitive function, gray matter volume, and white matter integrity in the presymptomatic stage of chromosome 9 open reading frame 72 repeat expansion ().
Presymptomatic carriers (n = 18) and first-degree family members without a pathogenic expansion (healthy controls [HC], n = 15) underwent a standardized protocol of neuropsychological tests, T1-weighted MRI, and diffusion tensor imaging within our cohort study of autosomal dominant frontotemporal dementia (FTD). We investigated group differences in cognitive function, gray matter volume through voxel-based morphometry, and white matter integrity by means of tract-based spatial statistics. We correlated cognitive change with underlying gray or white matter.
Our data demonstrate lower scores on letter fluency, Stroop card I, and Stroop card III, accompanied by white matter integrity loss in tracts connecting the frontal lobe, the thalamic radiation, and tracts associated with motor functioning in presymptomatic compared with HC. In a subgroup of carriers above 40 years of age, we found gray matter volume loss in the thalamus, cerebellum, and parietal and temporal cortex. We found no significant relationship between subtle cognitive decline and underlying gray or white matter.
This study demonstrates that a decline in cognitive functioning, white matter integrity, and gray matter volumes are present in presymptomatic carriers. These findings suggest that neuropsychological assessment, T1-weighted MRI, and diffusion tensor imaging might be useful to identify early biomarkers in the presymptomatic stage of FTD or amyotrophic lateral sclerosis.
研究染色体 9 开放阅读框 72 重复扩展（）在无症状前阶段的认知功能、灰质体积和白质完整性。
在我们的常染色体显性额颞叶痴呆（FTD）队列研究中，对无症状携带者（n=18）和无致病性扩展的一级亲属（健康对照[HC]，n=15）进行了标准化神经心理学测试、T1 加权 MRI 和弥散张量成像。我们通过基于体素的形态测量学研究了认知功能的组间差异，通过基于轨迹的空间统计学研究了灰质体积和白质完整性。我们将认知变化与潜在的灰质或白质相关联。
我们的数据表明，在无症状携带者中，字母流畅性、Stroop 卡片 I 和 Stroop 卡片 III 的得分较低，并且与额叶、丘脑辐射和与运动功能相关的轨迹相连接的白质完整性丧失。在年龄在 40 岁以上的携带者亚组中，我们发现丘脑、小脑和顶叶和颞叶皮质的灰质体积减少。我们没有发现细微认知下降与潜在的灰质或白质之间存在显著关系。
本研究表明，认知功能下降、白质完整性和灰质体积在无症状携带者中存在。这些发现表明，神经心理学评估、T1 加权 MRI 和弥散张量成像可能有助于在 FTD 或肌萎缩侧索硬化的无症状前阶段识别早期生物标志物。
