Laboratory of Epidemiology, Neuroimaging and Telemedicine, IRCCS Istituto Centro San Giovanni di Dio, Fatebenefratelli, Brescia, Italy.
NeuroBioGen Lab-Memory Clinic, IRCCS Istituto Centro San Giovanni di Dio, Fatebenefratelli, Brescia, Italy.
Alzheimers Dement. 2014 Oct;10(5 Suppl):S354-S363.e1. doi: 10.1016/j.jalz.2013.09.009. Epub 2014 Jan 10.
To investigate the patterns of brain atrophy, white matter (WM) tract changes, and functional connectivity (FC) abnormalities in asymptomatic granulin (GRN) mutation carriers.
Ten cognitively normal subjects (five mutation carriers, GRN+; years to estimated disease onset: 12±7; five mutation noncarriers, GRN-) underwent a clinical and imaging (structural, diffusion tensor, and resting-state functional magnetic resonance imaging) assessment. Brain atrophy was measured with cortical thickness analysis, WM abnormalities with tract-based spatial statistics, and FC with independent component analysis.
GRN+ showed smaller cortical thickness than GRN- in the right orbitofrontal and precentral gyrus and left rostral middle frontal gyrus. WM tracts abnormalities were limited to increased axial diffusivity in the right cingulum, superior longitudinal fasciculus, and corticospinal tract. There were no differences in FC of resting-state networks.
Brain atrophy and WM tract abnormalities in frontal-parietal circuits can be detected at least a decade before the estimated symptom onset in asymptomatic mutation carriers.
研究无症状颗粒蛋白前体（GRN）突变携带者的脑萎缩、白质（WM）束变化和功能连接（FC）异常模式。
十名认知正常的受试者（五名突变携带者，GRN+；预计发病时间：12±7 年；五名突变非携带者，GRN-）接受了临床和影像学（结构、弥散张量和静息状态功能磁共振成像）评估。通过皮质厚度分析测量脑萎缩，通过基于束的空间统计学测量 WM 异常，通过独立成分分析测量 FC。
GRN+的右侧眶额和中央前回以及左侧额中回的皮质厚度小于 GRN-。WM 束异常仅限于右侧扣带束、上纵束和皮质脊髓束的轴向弥散度增加。静息状态网络的 FC 无差异。
在无症状突变携带者预计症状出现前至少十年，就可以检测到额顶叶回路的脑萎缩和 WM 束异常。
