PDF(Pubmed)
Abstract：
Posterior cortical atrophy (PCA) and dementia with Lewy bodies (DLB) show distinct atrophy and overlapping hypometabolism profiles, but it is unknown how disruptions in structural and functional connectivity compare between these disorders and whether breakdowns in connectivity relate to either atrophy or hypometabolism. Thirty amyloid-positive PCA patients, 24 amyloid-negative DLB patients and 30 amyloid-negative cognitively unimpaired (CU) healthy individuals were recruited at Mayo Clinic, Rochester, MN, and underwent a 3T head MRI, including structural MRI, resting state functional MRI (rsfMRI) and diffusion tensor imaging (DTI) sequences, as well as [18F] fluorodeoxyglucose (FDG) PET. We assessed functional connectivity within and between 12 brain networks using rsfMRI and the CONN functional connectivity toolbox and calculated regional DTI metrics using the Johns Hopkins atlas. Multivariate linear-regression models corrected for multiple comparisons and adjusted for age and sex compared DTI metrics and within-network and between-network functional connectivity across groups. Regional gray-matter volumes and FDG-PET standard uptake value ratios (SUVRs) were calculated and analyzed at the voxel-level using SPM12. We used univariate linear-regression models to investigate the relationship between connectivity measures, gray-matter volume, and FDG-PET SUVR. On DTI, PCA showed degeneration in occipito-parietal white matter, posterior thalamic radiations, splenium of the corpus collosum and sagittal stratum compared to DLB and CU, with greater degeneration in the temporal white matter and the fornix compared to CU. We observed no white-matter degeneration in DLB compared to CU. On rsfMRI, reduced within-network connectivity was present in dorsal and ventral default mode networks (DMN) and the dorsal-attention network in PCA compared to DLB and CU, with reduced within-network connectivity in the visual and sensorimotor networks compared to CU. DLB showed reduced connectivity in the cerebellar network compared to CU. Between-network analysis showed increased connectivity in both cerebellar-to-sensorimotor and cerebellar-to-dorsal attention network connectivity in PCA and DLB. PCA showed reduced anterior DMN-to-cerebellar and dorsal attention-to-sensorimotor connectivity, while DLB showed reduced posterior DMN-to-sensorimotor connectivity compared to CU. PCA showed reduced dorsal DMN-to-visual connectivity compared to DLB. The multimodal analysis revealed weak associations between functional connectivity and volume in PCA, and between functional connectivity and metabolism in DLB. These findings suggest that PCA and DLB have unique connectivity alterations, with PCA showing more widespread disruptions in both structural and functional connectivity; yet some overlap was observed with both disorders showing increased connectivity from the cerebellum.
摘要：
后皮质萎缩（PCA）和路易体痴呆（DLB）表现出明显的萎缩和重叠的低代谢特征，但尚不清楚这些疾病之间结构和功能连接中断的比较以及连接中断是否与萎缩或低代谢有关.30名淀粉样蛋白阳性PCA患者，梅奥诊所招募了24名淀粉样蛋白阴性DLB患者和30名淀粉样蛋白阴性认知未受损（CU）健康个体，罗切斯特,MN,做了3T头颅MRI,包括结构核磁共振,静息态功能磁共振成像（rsfMRI）和扩散张量成像（DTI）序列，以及[18F]氟脱氧葡萄糖(FDG)PET。我们使用rsfMRI和CONN功能连接工具箱评估了12个大脑网络内部和之间的功能连接，并使用约翰霍普金斯大学图集计算了区域DTI指标。多元线性回归模型校正了多重比较，并校正了年龄和性别，比较了DTI指标以及各组之间的网络内和网络间功能连通性。使用SPM12在体素水平上计算并分析区域灰质体积和FDG-PET标准摄取值比率（SUVR）。我们使用单变量线性回归模型来研究连通性度量之间的关系，灰质体积，和FDG-PETSUVR。在DTI上,PCA显示枕顶白质变性，后丘脑辐射，与DLB和CU相比，胶体和矢状层的脾，与CU相比，颞叶白质和穹窿的变性更大。与CU相比，我们在DLB中未观察到白质变性。在rsfMRI上，与DLB和CU相比，PCA中的背侧和腹侧默认模式网络（DMN）和背侧注意力网络中存在减少的网络内连通性，与CU相比，视觉和感觉运动网络中的网络内连通性降低。与CU相比，DLB显示小脑网络的连通性降低。网络间分析显示，PCA和DLB中小脑到感觉运动和小脑到背侧注意网络连通性均增加。PCA显示前DMN到小脑和背侧注意力到感觉运动的连通性降低，而DLB显示与CU相比，后部DMN与感觉运动连接减少。与DLB相比，PCA显示背侧DMN-视觉连通性降低。多模态分析揭示了PCA中功能连通性和体积之间的弱关联，以及DLB中功能连接和代谢之间的关系。这些发现表明PCA和DLB具有独特的连通性改变，PCA在结构和功能连接方面显示出更广泛的破坏；然而，在两种显示小脑连接增加的疾病中观察到一些重叠。
