Tau accumulation affecting white matter tracts is an early neuropathological feature of late-onset Alzheimer's disease (LOAD). There is a need to ascertain methods for the detection of early LOAD features to help with disease prevention efforts. The microstructure of these tracts and anatomical brain connectivity can be assessed by analyzing diffusion MRI (dMRI) data. Considering that family history increases the risk of developing LOAD, we explored the microstructure of white matter through dMRI in 23 cognitively normal adults who are offspring of patients with Late-Onset Alzheimer's Disease (O-LOAD) and 22 control subjects (CS) without family history of AD. We also evaluated the relation of white matter microstructure metrics with cortical thickness, volumetry, in vivo amyloid deposition (with the help of PiB positron emission tomography -PiB-PET) and regional brain metabolism (as FDG-PET) measures. Finally we studied the association between cognitive performance and white matter microstructure metrics. O-LOAD exhibited lower fiber density and fractional anisotropy in the posterior portion of the corpus callosum and right fornix when compared to CS. Among O-LOAD, reduced fiber density was associated with lower amyloid deposition in the right hippocampus, and greater cortical thickness in the left precuneus, while higher mean diffusivity was related with greater cortical thickness of the right superior temporal gyrus. Additionally, compromised white matter microstructure was associated with poorer semantic fluency. In conclusion, white matter microstructure metrics may reveal early differences in O-LOAD by virtue of parental history of the disorder, when compared to CS without a family history of LOAD. We demonstrate that these differences are associated with lower fiber density in the posterior portion of the corpus callosum and the right fornix.

中文翻译：

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认知正常成年人中的白质纤维密度异常有发生晚发型阿尔茨海默氏病的风险。

Tau积累影响白质道是晚期阿尔茨海默氏病（LOAD）的早期神经病理学特征。需要确定用于检测早期LOAD特征的方法以帮助疾病预防工作。可以通过分析弥散MRI（dMRI）数据来评估这些管道的微结构和大脑的解剖学连通性。考虑到家族史增加了发生LOAD的风险，我们通过dMRI探索了23名认知正常成年人的白质的微观结构，这些成年人是晚期阿尔茨海默氏病（O-LOAD）患者的后代，还有22名没有家人的对照组AD的历史。我们还评估了白质微观结构指标与皮质厚度，体积，体内淀粉样蛋白沉积（借助PiB正电子发射断层扫描-PiB-PET）和局部脑代谢（作为FDG-PET）措施。最后，我们研究了认知能力与白质微观结构指标之间的关联。与CS相比，O-LOAD在call体和右穹ni后部表现出较低的纤维密度和分数各向异性。在O-LOAD中，纤维密度的降低与右海马中淀粉样蛋白沉积的减少和左前神经的皮质厚度的增加有关，而平均扩散系数较高与右颞上回的皮质厚度的增加有关。另外，受损的白质微观结构与较差的语义流利度有关。结论，与没有LOAD家族史的CS相比，白质微结构指标可能会通过患儿的父母病史揭示O-LOAD的早期差异。我们证明这些差异与call体和右穹ni后部较低的纤维密度有关。