Aishwarya Pradeep, Sheelakumari Raghavan, Scott A. Przybelski, Gregory M. Preboske, Christopher G. Schwarz, Val J. Lowe, David S. Knopman, Ronald C. Petersen, Clifford R. Jack, Jonathan Graff-Radford, Petrice M. Cogswell, Prashanthi Vemuri
{"title":"基于法泽卡斯视觉评估量表的白质高密度能否为阿尔茨海默病的病理变化提供信息?","authors":"Aishwarya Pradeep, Sheelakumari Raghavan, Scott A. Przybelski, Gregory M. Preboske, Christopher G. Schwarz, Val J. Lowe, David S. Knopman, Ronald C. Petersen, Clifford R. Jack, Jonathan Graff-Radford, Petrice M. Cogswell, Prashanthi Vemuri","doi":"10.1186/s13195-024-01525-5","DOIUrl":null,"url":null,"abstract":"White matter hyperintensities (WMH) are considered hallmark features of cerebral small vessel disease and have recently been linked to Alzheimer’s disease (AD) pathology. Their distinct spatial distributions, namely periventricular versus deep WMH, may differ by underlying age-related and pathobiological processes contributing to cognitive decline. We aimed to identify the spatial patterns of WMH using the 4-scale Fazekas visual assessment and explore their differential association with age, vascular health, AD imaging markers, namely amyloid and tau burden, and cognition. Because our study consisted of scans from GE and Siemens scanners with different resolutions, we also investigated inter-scanner reproducibility and combinability of WMH measurements on imaging. We identified 1144 participants from the Mayo Clinic Study of Aging consisting of a population-based sample from Olmsted County, Minnesota with available structural magnetic resonance imaging (MRI), amyloid, and tau positron emission tomography (PET). WMH distribution patterns were assessed on FLAIR-MRI, both 2D axial and 3D, using Fazekas ratings of periventricular and deep WMH severity. We compared the association of periventricular and deep WMH scales with vascular risk factors, amyloid-PET, and tau-PET standardized uptake value ratio, automated WMH volume, and cognition using Pearson partial correlation after adjusting for age. We also evaluated vendor compatibility and reproducibility of the Fazekas scales using intraclass correlations (ICC). Periventricular and deep WMH measurements showed similar correlations with age, cardiometabolic conditions score (vascular risk), and cognition, (p < 0.001). Both periventricular WMH and deep WMH showed weak associations with amyloidosis (R = 0.07, p = < 0.001), and none with tau burden. We found substantial agreement between data from the two scanners for Fazekas measurements (ICC = 0.82 and 0.74). The automated WMH volume had high discriminating power for identifying participants with Fazekas ≥ 2 (area under curve = 0.97) and showed poor correlation with amyloid and tau PET markers similar to the visual grading. Our study investigated risk factors underlying WMH spatial patterns and their impact on global cognition, with no discernible differences between periventricular and deep WMH. We observed minimal impact of amyloidosis on WMH severity. 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We identified 1144 participants from the Mayo Clinic Study of Aging consisting of a population-based sample from Olmsted County, Minnesota with available structural magnetic resonance imaging (MRI), amyloid, and tau positron emission tomography (PET). WMH distribution patterns were assessed on FLAIR-MRI, both 2D axial and 3D, using Fazekas ratings of periventricular and deep WMH severity. We compared the association of periventricular and deep WMH scales with vascular risk factors, amyloid-PET, and tau-PET standardized uptake value ratio, automated WMH volume, and cognition using Pearson partial correlation after adjusting for age. We also evaluated vendor compatibility and reproducibility of the Fazekas scales using intraclass correlations (ICC). Periventricular and deep WMH measurements showed similar correlations with age, cardiometabolic conditions score (vascular risk), and cognition, (p < 0.001). 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引用次数: 0
摘要
白质高密度(WMH)被认为是脑小血管疾病的标志性特征,最近又被认为与阿尔茨海默病(AD)病理有关。它们不同的空间分布,即脑室周围 WMH 和深部 WMH,可能因导致认知能力下降的潜在年龄相关过程和病理生物学过程而有所不同。我们的目的是使用 4 级法泽卡斯视觉评估法确定 WMH 的空间模式,并探讨它们与年龄、血管健康、AD 影像标记物(即淀粉样蛋白和 tau 负荷)和认知能力的不同关联。由于我们的研究包括不同分辨率的通用电气和西门子扫描仪的扫描,因此我们还研究了扫描仪之间的可重复性以及成像中 WMH 测量的可组合性。我们从梅奥诊所老龄化研究(Mayo Clinic Study of Aging)中确定了 1144 名参与者,这些参与者是来自明尼苏达州奥姆斯特德县的人口样本,具有结构性磁共振成像 (MRI)、淀粉样蛋白和 tau 正电子发射断层扫描 (PET)。通过FLAIR-MRI的二维轴向和三维成像对WMH分布模式进行评估,并使用Fazekas对脑室周围和深部WMH严重程度进行评级。我们比较了脑室周围和深部 WMH 评级与血管风险因素、淀粉样蛋白-PET 和 tau-PET 标准化摄取值比、自动 WMH 体积以及认知能力之间的关系,在调整年龄后使用了皮尔逊偏相关性。我们还使用类内相关性(ICC)评估了 Fazekas 量表的供应商兼容性和可重复性。脑室周围和深部 WMH 测量值与年龄、心脏代谢状况评分(血管风险)和认知能力显示出相似的相关性(p < 0.001)。脑室周围 WMH 和深部 WMH 与淀粉样变性(R = 0.07,p = < 0.001)有微弱的相关性,但与 tau 负荷无相关性。我们发现两台扫描仪的法泽卡斯测量数据非常一致(ICC = 0.82 和 0.74)。自动 WMH 容量对识别 Fazekas ≥ 2 的参与者有很高的鉴别力(曲线下面积 = 0.97),但与淀粉样蛋白和 tau PET 标记的相关性较差,与视觉分级类似。我们的研究调查了WMH空间模式背后的风险因素及其对整体认知的影响,发现脑室周围和深部WMH之间没有明显差异。我们观察到淀粉样变性对 WMH 严重程度的影响极小。这些发现以及 WMH 数据的扫描仪间可重复性的增强,表明在血管对认知障碍和痴呆生物标志物研究的贡献方面,通过统一方案评估的扫描仪间数据具有可组合性。
Can white matter hyperintensities based Fazekas visual assessment scales inform about Alzheimer’s disease pathology in the population?
White matter hyperintensities (WMH) are considered hallmark features of cerebral small vessel disease and have recently been linked to Alzheimer’s disease (AD) pathology. Their distinct spatial distributions, namely periventricular versus deep WMH, may differ by underlying age-related and pathobiological processes contributing to cognitive decline. We aimed to identify the spatial patterns of WMH using the 4-scale Fazekas visual assessment and explore their differential association with age, vascular health, AD imaging markers, namely amyloid and tau burden, and cognition. Because our study consisted of scans from GE and Siemens scanners with different resolutions, we also investigated inter-scanner reproducibility and combinability of WMH measurements on imaging. We identified 1144 participants from the Mayo Clinic Study of Aging consisting of a population-based sample from Olmsted County, Minnesota with available structural magnetic resonance imaging (MRI), amyloid, and tau positron emission tomography (PET). WMH distribution patterns were assessed on FLAIR-MRI, both 2D axial and 3D, using Fazekas ratings of periventricular and deep WMH severity. We compared the association of periventricular and deep WMH scales with vascular risk factors, amyloid-PET, and tau-PET standardized uptake value ratio, automated WMH volume, and cognition using Pearson partial correlation after adjusting for age. We also evaluated vendor compatibility and reproducibility of the Fazekas scales using intraclass correlations (ICC). Periventricular and deep WMH measurements showed similar correlations with age, cardiometabolic conditions score (vascular risk), and cognition, (p < 0.001). Both periventricular WMH and deep WMH showed weak associations with amyloidosis (R = 0.07, p = < 0.001), and none with tau burden. We found substantial agreement between data from the two scanners for Fazekas measurements (ICC = 0.82 and 0.74). The automated WMH volume had high discriminating power for identifying participants with Fazekas ≥ 2 (area under curve = 0.97) and showed poor correlation with amyloid and tau PET markers similar to the visual grading. Our study investigated risk factors underlying WMH spatial patterns and their impact on global cognition, with no discernible differences between periventricular and deep WMH. We observed minimal impact of amyloidosis on WMH severity. These findings, coupled with enhanced inter-scanner reproducibility of WMH data, suggest the combinability of inter-scanner data assessed by harmonized protocols in the context of vascular contributions to cognitive impairment and dementia biomarker research.
期刊介绍:
Alzheimer's Research & Therapy is an international peer-reviewed journal that focuses on translational research into Alzheimer's disease and other neurodegenerative diseases. It publishes open-access basic research, clinical trials, drug discovery and development studies, and epidemiologic studies. The journal also includes reviews, viewpoints, commentaries, debates, and reports. All articles published in Alzheimer's Research & Therapy are included in several reputable databases such as CAS, Current contents, DOAJ, Embase, Journal Citation Reports/Science Edition, MEDLINE, PubMed, PubMed Central, Science Citation Index Expanded (Web of Science) and Scopus.