Increased Cortical Thickness and Caudate Volume Precede Atrophy in PSEN1 Mutation Carriers
Increased Cortical Thickness and Caudate Volume Precede Atrophy in PSEN1 Mutation Carriers
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DOI：
10.3233/jad-2010-100678
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发表时间：
2010-01-01
影响因子：
4
通讯作者：
Sanchez-Valle, Raquel
中科院分区：
文献类型：
--
作者：
Fortea, Juan;Sala-Llonch, Roser;Sanchez-Valle, Raquel
家族性阿尔茨海默病的神经影像学研究允许在临床发作之前调查疾病过程。我们进行了半自动MRI分析，以评估皮质厚度（CTh），灰质（GM）的体积，和GM扩散指数在PSEN 1突变携带者（MC）。我们招募了来自4个PSEN 1突变家族（L286 P、M139 T、K239 N）的11名MC和6名家族性和12名非家族性健康对照。MC分为无症状（n = 6）或有症状（n = 5）。受试者接受结构和弥散加权3特斯拉MRI扫描。计算皮质下结构的CTh和GM体积和扩散系数指数，并进行组间比较。用基于体素的形态学方法重新分析结构图像。测量了脑脊液淀粉样蛋白β（1-42）水平（A β）。我们发现症状性MC表现为广泛的皮质变薄，尤其是楔前叶和顶颞区（p < 0.01），与对照组相比，这些区域的平均扩散率（MD）增加。出乎意料的是，与HC相比，在预测的疾病发作年龄之前9.9年的无症状MC表现出楔前叶和顶颞区的CTh增加（p <0.01），尾状核体积增加（p < 0.01），并且这些区域的MD减少（p < 0.05）。在MC中，CTh与校正的年龄相关。在AMC中，A β值在正常范围内。总之，在早期临床前阶段，在楔前叶和顶颞区和尾状核体积增加PSEN 1 MC CTh和减少，此后随着疾病的进展。无症状和有症状MC中MD的不同趋势表明不同的微结构变化是形成对比的形态测量结果的基础。反应性神经元肥大或/和炎症可能是无症状MC中CTh增加和MD减少的原因。
Neuroimaging studies of familial Alzheimer's disease allow investigation of the disease process before clinical onset. We performed semi-automated MRI analysis to evaluate cortical thickness (CTh), grey matter (GM) volumes, and GM diffusivity indexes in PSEN1 mutation carriers (MC). We recruited 11 MC from 4 families with PSEN1 mutations (L286P, M139T, K239N) and 6 familial and 12 non-familial healthy controls. MC were classified as either asymptomatic (n = 6) or symptomatic (n = 5). Subjects underwent structural and diffusion-weighted 3-Tesla MRI scanning. CTh and GM volumes of subcortical structures and diffusivity indexes were calculated and group comparisons were performed. Structural images were reanalyzed with voxel-based morphometry methodology. Cerebrospinal fluid amyloid-beta(1-42) levels (A beta) were measured. We found that symptomatic MC presented widespread cortical thinning, especially in precuneus and parietotemporal areas (p < 0.01) and increased mean diffusivity (MD) in these areas compared to controls. Unexpectedly, asymptomatic MC, 9.9 years prior to the predicted age of disease onset, presented increased CTh in the precuneus and parietotemporal areas (p < 0.01), increased caudate volumes (p < 0.01), and decreased MD (p < 0.05) in these areas compared to HC. In MC, CTh correlated with adjusted age. A beta values were within normal limits in AMC. In conclusion, at early preclinical stages, CTh in the precuneus and parietotemporal regions and caudate volume increase in PSEN1 MC and decrease thereafter with disease progression. The different trends in MD in asymptomatic and symptomatic MC suggest that different microstructural changes underlie the contrasting morphometric findings. Reactive neuronal hypertrophy or/and inflammation may account for increased CTh and decreased MD in asymptomatic MC.