Age-related functional brain changes in FMR1 premutation carriers.
Age-related functional brain changes in FMR1 premutation carriers.
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DOI：
10.1016/j.nicl.2017.12.016
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Stanfield AC
中科院分区：
文献类型：
--
作者：
Brown SSG;Basu S;Whalley HC;Kind PC;Stanfield AC
FMR1预突变使男性患脆性x相关震颤共济失调综合征（FXTAS）的神经退行性疾病的风险为40-60%。FXTAS是一种迟发性疾病，主要涉及震颤和共济失调的进行性症状，以及一些患者可发展为痴呆的认知能力下降。目前，尚不清楚在坦白症状出现之前，是否可以在运动区检测到脑功能的改变。因此，本研究旨在首次在无症状前突变人群中利用fMRI运动任务。本横断面研究招募了未诊断为FXTAS的突变前携带者（n = 17）和一组健康男性对照组（n = 17），年龄范围为24-68岁。本研究利用神经影像学、分子和临床测量，采用fMRI手指敲击任务，采用由顺序手指敲击、随机手指敲击和休息条件组成的块设计。成像分析对比了顺序条件和随机条件，以研究任务需求变化时的激活变化。此外，使用CATSYS-2000系统测量参与者的震颤、协调和平衡，并使用实时定量PCR方法从外周血样本中定量测量FMR1 mRNA。在顺序敲击手指和随机敲击手指时，突变前携带者的小脑激活明显低于对照组（fwecor < 0.001）。此外，与对照组相比，携带组的海马、下顶叶皮层和颞叶皮层存在显著的年龄相互作用，这源于大脑活动与年龄之间的负相关关系（FWEcorr < 0.001）。在这里，我们首次提出了脆性X基因突变携带者早期运动相关神经退行性变的基于功能成像的证据。这些变化存在于FXTAS的诊断之前，并且在老年携带者中最大，这表明它们可能表明FXTAS的脆弱性。作者在FMR1预突变男性携带者的横断功能磁共振研究中发现，在手指敲击任务中，当任务需求改变时，小脑的BOLD激活减少。在颞顶区，携带者表现出x组年龄的BOLD反应相互作用，这些变化在脆性x相关震颤/失联综合征（FXTAS）的诊断之前就存在。
The FMR1 premutation confers a 40–60% risk for males of developing a neurodegenerative disease called the Fragile X-associated Tremor Ataxia Syndrome (FXTAS). FXTAS is a late-onset disease that primarily involves progressive symptoms of tremor and ataxia, as well as cognitive decline that can develop into dementia in some patients. At present, it is not clear whether changes to brain function are detectable in motor regions prior to the onset of frank symptomatology. The present study therefore aimed to utilize an fMRI motor task for the first time in an asymptomatic premutation population. Premutation carriers without a diagnosis of FXTAS (n = 17) and a group of healthy male controls (n = 17), with an age range of 24–68 years old, were recruited for this cross-sectional study. This study utilized neuroimaging, molecular and clinical measurements, employing an fMRI finger-tapping task with a block design consisting of sequential finger-tapping, random finger-tapping and rest conditions. The imaging analysis contrasted the sequential and random conditions to investigate activation changes in response to a change in task demand. Additionally, measurements were obtained of participant tremor, co-ordination and balance using the CATSYS-2000 system and measures of FMR1 mRNA were quantified from peripheral blood samples using quantitative real-time PCR methodology. Premutation carriers demonstrated significantly less cerebellar activation than controls during sequential versus random finger tapping (FWEcorr < 0.001). In addition, there was a significant age by group interaction in the hippocampus, inferior parietal cortex and temporal cortex originating from a more negative relationship between brain activation and age in the carrier group compared to the controls (FWEcorr < 0.001). Here, we present for the first time functional imaging-based evidence for early movement-related neurodegeneration in Fragile X premutation carriers. These changes pre-exist the diagnosis of FXTAS and are greatest in older carriers suggesting that they may be indicative of FXTAS vulnerability. The authors present a cross-sectional fMRI study in male carriers of the FMR1 premutation Carriers show decreased BOLD activation at the cerebellum in response to change in task demand in a finger-tapping task Carriers exhibit a group x age interaction of BOLD response in the temporoparietal area These changes pre-exist the diagnosis of the Fragile X-associated Tremor/Ataxia Syndrome (FXTAS)
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影响因子：
9.9
作者：
Leehey, M. A.;Berry-Kravis, E.;Hagerman, P. J.
通讯作者：
Hagerman, P. J.
DOI：
10.1007/s12311-016-0799-4
发表时间：
2016-10
期刊：
Cerebellum (London, England)
影响因子：
--
作者：
Hall DA;Robertson E;Shelton AL;Losh MC;Mila M;Moreno EG;Gomez-Anson B;Martínez-Cerdeño V;Grigsby J;Lozano R;Hagerman R;Maria LS;Berry-Kravis E;O'Keefe JA
通讯作者：
O'Keefe JA
影响因子：
4.8
作者：
Duarte, Joao Valente;Faustino, Ricardo;Castelo-Branco, Miguel
通讯作者：
Castelo-Branco, Miguel
影响因子：
8.6
作者：
Hashimoto, Ryu-ichiro;Srivastava, Siddharth;Rivera, Susan M.
通讯作者：
Rivera, Susan M.
影响因子：
9.9
作者：
Hall, DA;Berry-Kravis, E;Leehey, MA
通讯作者：
Leehey, MA