Dr Mario Torso, Oxford Brain Diagnostics Ltd, Oxford, UK,
J Prev Alzheimers Dis. 2022;9(4):769-779. doi: 10.14283/jpad.2022.59.
Alzheimer's disease (AD) neuropathology reveals progressive microstructural alterations of cortical architecture. Recent studies reported intriguing biphasic trajectories of cortical structural changes in the early stages of Alzheimer's disease (AD), comprising decreased mean diffusivity (MD) and increased cortical thickness in cognitively normal amyloid-positive individuals, ahead of increases and decreases, respectively, in subsequent disease stages.
To better understand the cytoarchitectural correlates of these observations, we assessed novel cortical diffusion tensor imaging (DTI) metrics that are correlated with disruption of cortical minicolumns and protein deposition.
Cross-sectional and longitudinal analysis of whole brain and temporal lobe cortical diffusivity measures. Investigation of associations between baseline cortical diffusivity values and 24-month longitudinal structural-MRI changes. Investigations of the relationships between cortical diffusivity measures and biomarkers of neuroinflammation.
Alzheimer's Disease Neuroimaging Initiative (ADNI).
Twenty-four amyloid-negative controls (CN-), 28 amyloid-positive controls (CN+), 46 amyloid-positive subjects with mild cognitive impairment (MCI+) and 22 amyloid-positive subjects with AD were included.
3DT1 and DTI scans at baseline and approximately 24-month follow-up were used to calculate cortical MD and three novel cortical diffusivity measures: the angle between the radial minicolumnar axis and the principal diffusion direction (AngleR); the diffusion components perpendicular to the minicolumns (PerpPD+), and the principal diffusion component parallel with the minicolumns (ParlPD). Cortical macrostructural measurements (cortical volume fraction and cortical thickness), were used to test the hypothesis that baseline cortical diffusivity values can predict change in structural MRI outcomes over approximately 24 months. CSF soluble TREM2 and progranulin (PGRN) concentrations were used to investigate associations with microglial activity and potentially other aspects of neuroinflammation.
Cortical diffusivity metrics revealed a dependence on disease stage, with AngleR and PerpPD+ displaying biphasic relationships and ParlPD a monotonic relationship with clinical severity. The novel metrics were able to differentiate between Amyloid+ and Amyloid- controls (AngleR) and to differentiate among disease stages along the AD continuum (PerpPD+). Linear regression revealed significant associations between baseline cortical diffusivity values and subsequent 24-month longitudinal structural-MRI changes. AngleR values were significantly associated with CSF sTREM2 and PGRN concentrations.
Cortical diffusivity parameters reflecting minicolumnar organization and neuroinflammation may provide a sensitive and biologically interpretable measurement of cortex quality and microstructure across the AD continuum.
阿尔茨海默病（AD）的神经病理学显示皮质结构的进行性微观结构改变。最近的研究报告了在阿尔茨海默病（AD）的早期阶段皮质结构变化的有趣双相轨迹，包括认知正常的淀粉样蛋白阳性个体的平均弥散度（MD）降低和皮质厚度增加，分别在随后的疾病阶段增加和减少之前。
为了更好地理解这些观察结果的细胞结构相关性，我们评估了与皮质小柱破坏和蛋白质沉积相关的新型皮质扩散张量成像（DTI）指标。
全脑和颞叶皮质弥散度测量的横断面和纵向分析。研究基线皮质弥散度值与 24 个月纵向结构-MRI 变化之间的关联。研究皮质弥散度值与神经炎症生物标志物之间的关系。
阿尔茨海默病神经影像学倡议（ADNI）。
24 名淀粉样阴性对照（CN-）、28 名淀粉样阳性对照（CN+）、46 名淀粉样阳性轻度认知障碍（MCI+）和 22 名淀粉样阳性 AD 患者被纳入研究。
在基线和大约 24 个月随访时使用 3DT1 和 DTI 扫描来计算皮质 MD 和三个新的皮质弥散度指标：径向小柱轴与主扩散方向之间的角度（AngleR）；垂直于小柱的扩散分量（PerpPD+）和与小柱平行的主扩散分量（ParlPD）。皮质宏观结构测量（皮质体积分数和皮质厚度）用于检验基线皮质弥散度值是否可以预测大约 24 个月内结构 MRI 结果的变化的假设。CSF 可溶性 TREM2 和颗粒蛋白（PGRN）浓度用于研究与小胶质细胞活性和潜在其他神经炎症方面的关联。
皮质弥散度指标显示出对疾病阶段的依赖性，AngleR 和 PerpPD+ 显示出双相关系，而 ParlPD 与临床严重程度呈单调关系。新指标能够区分淀粉样阳性和淀粉样阴性对照（AngleR），并沿着 AD 连续体区分疾病阶段（PerpPD+）。线性回归显示基线皮质弥散度值与随后 24 个月的纵向结构-MRI 变化之间存在显著关联。AngleR 值与 CSF sTREM2 和 PGRN 浓度显著相关。
反映小柱组织和神经炎症的皮质弥散度参数可能为 AD 连续体中皮质质量和微观结构提供敏感且具有生物学解释的测量。
