From the Division of Neurology, Department of Medicine (C.J., G.-Y.R.H., I.T., H.L., P.S., P.B.-K., A.J.S., H.H.F.), Department of Physics and Astronomy (K.D., S.M., M.G., V.S.), and Department of Pathology and Laboratory Medicine (I.R.M.), University of British Columbia, Vancouver, Canada; and Department of Neuroscience (M.B., R.R.), Mayo Clinic, Jacksonville, FL.
Neurology. 2013 Oct 8;81(15):1322-31. doi: 10.1212/WNL.0b013e3182a8237e. Epub 2013 Sep 4.
In this prospective cohort study, we investigated cerebral glucose metabolism reductions on [(18)F]-fluorodeoxyglucose (FDG)-PET in progranulin (GRN) mutation carriers prior to frontotemporal dementia (FTD) onset.
Nine mutation carriers (age 51.5 ± 13.5 years) and 11 noncarriers (age 52.7 ± 9.5 years) from 5 families with FTD due to GRN mutations underwent brain scanning with FDG-PET and MRI and clinical evaluation. Normalized FDG uptake values were calculated with reference to the pons. PET images were analyzed with regions of interest (ROI) and statistical parametric mapping (SPM) approaches.
Compared with noncarriers, GRN mutation carriers had a lowered anterior-to-posterior (AP) ratio of FDG uptake (0.86 ± 0.09 vs 0.92 ± 0.05) and less left-right asymmetry, consistent with an overall pattern of right anterior cerebral hypometabolism. This pattern was observed regardless of whether they were deemed clinically symptomatic no dementia or asymptomatic. Individual ROIs with lowered FDG uptake included right anterior cingulate, insula, and gyrus rectus. SPM analysis supported and extended these findings, demonstrating abnormalities in the right and left medial frontal regions, right insular cortex, right precentral and middle frontal gyri, and right cerebellum. Right AP ratio was correlated with cognitive and clinical scores (modified Mini-Mental State Examination r = 0.74; Functional Rating Scale r = -0.73) but not age and years to estimated onset in mutation carriers.
The frontotemporal lobar degenerative process associated with GRN mutations appears to begin many years prior to the average age at FTD onset (late 50s-early 60s). Right medial and ventral frontal cortex and insula may be affected in this process but the specific regional patterns associated with specific clinical variants remain to be elucidated.
在这项前瞻性队列研究中，我们研究了在额颞叶痴呆（FTD）发病前，颗粒体蛋白基因（GRN）突变携带者的正电子发射断层扫描术（PET）中[（18）F]氟脱氧葡萄糖（FDG）摄取减少的情况。
来自 5 个 GRN 突变导致 FTD 的家族的 9 名突变携带者（年龄 51.5 ± 13.5 岁）和 11 名非携带者（年龄 52.7 ± 9.5 岁）接受了 FDG-PET 和 MRI 脑扫描以及临床评估。用桥脑作为参照计算了 FDG 摄取的标准化值。使用感兴趣区域（ROI）和统计参数映射（SPM）方法分析 PET 图像。
与非携带者相比，GRN 突变携带者的 FDG 摄取的前后（AP）比率降低（0.86 ± 0.09 比 0.92 ± 0.05），左右不对称减少，与右前大脑代谢不足的整体模式一致。这种模式在无论他们是否被认为是临床有症状的无痴呆或无症状的情况下都存在。FDG 摄取降低的个体 ROI 包括右侧前扣带回、岛叶和直回。SPM 分析支持并扩展了这些发现，显示右内侧和左额区域、右侧岛叶皮质、右侧中央前回和额中回以及右侧小脑异常。右 AP 比率与认知和临床评分相关（改良的简易精神状态检查表 r = 0.74；功能评定量表 r = -0.73），但与携带者的年龄和发病前的年数无关。
与 GRN 突变相关的额颞叶退行性变过程似乎在 FTD 发病的平均年龄（50 多岁至 60 岁出头）之前很多年就开始了。右侧内侧和腹侧额叶皮质和岛叶可能在此过程中受到影响，但与特定临床变异相关的具体区域模式仍有待阐明。
