Abstract：
BACKGROUND: We investigated the effect of perivascular spaces (PVS) volume on speeded executive function (sEF), as mediated by white matter hyperintensities (WMH) volume and plasma glial fibrillary acidic protein (GFAP) in neurodegenerative diseases.
METHODS: A mediation analysis was performed to assess the relationship between neuroimaging markers and plasma biomarkers on sEF in 333 participants clinically diagnosed with Alzheimer\'s disease/mild cognitive impairment, frontotemporal dementia, or cerebrovascular disease from the Ontario Neurodegenerative Disease Research Initiative.
RESULTS: PVS was significantly associated with sEF (c = -0.125 ± 0.054, 95% bootstrap confidence interval [CI] [-0.2309, -0.0189], p = 0.021). This effect was mediated by both GFAP and WMH.
CONCLUSIONS: In this unique clinical cohort of neurodegenerative diseases, we demonstrated that the effect of PVS on sEF was mediated by the presence of elevated plasma GFAP and white matter disease. These findings highlight the potential utility of imaging and plasma biomarkers in the current landscape of therapeutics targeting dementia.
CONCLUSIONS: Perivascular spaces (PVS) and white matter hyperintensities (WMH) are imaging markers of small vessel disease. Plasma glial fibrillary protein acidic protein (GFAP) is a biomarker of astroglial injury. PVS, WMH, and GFAP are relevant in executive dysfunction from neurodegeneration. PVS\'s effect on executive function was mediated by GFAP and white matter disease.
METHODS: A mediation analysis was performed to assess the relationship between neuroimaging markers and plasma biomarkers on sEF in 333 participants clinically diagnosed with Alzheimer\'s disease/mild cognitive impairment, frontotemporal dementia, or cerebrovascular disease from the Ontario Neurodegenerative Disease Research Initiative.
RESULTS: PVS was significantly associated with sEF (c = -0.125 ± 0.054, 95% bootstrap confidence interval [CI] [-0.2309, -0.0189], p = 0.021). This effect was mediated by both GFAP and WMH.
CONCLUSIONS: In this unique clinical cohort of neurodegenerative diseases, we demonstrated that the effect of PVS on sEF was mediated by the presence of elevated plasma GFAP and white matter disease. These findings highlight the potential utility of imaging and plasma biomarkers in the current landscape of therapeutics targeting dementia.
CONCLUSIONS: Perivascular spaces (PVS) and white matter hyperintensities (WMH) are imaging markers of small vessel disease. Plasma glial fibrillary protein acidic protein (GFAP) is a biomarker of astroglial injury. PVS, WMH, and GFAP are relevant in executive dysfunction from neurodegeneration. PVS\'s effect on executive function was mediated by GFAP and white matter disease.
摘要：
背景：我们研究了血管周围空间（PVS）体积对加速执行功能（sEF）的影响，在神经退行性疾病中由白质高信号（WMH）体积和血浆胶质纤维酸性蛋白（GFAP）介导。
方法：在333名临床诊断为阿尔茨海默病/轻度认知障碍的参与者中，进行了调解分析，以评估神经影像学标志物与血浆生物标志物对sEF的关系。额颞叶痴呆,或来自安大略省神经退行性疾病研究倡议的脑血管疾病。
结果：PVS与sEF显着相关（c=-0.125±0.054，95％自举置信区间[CI][-0.2309，-0.0189]，p=0.021)。该效应由GFAP和WMH两者介导。
结论：在这个独特的神经退行性疾病临床队列中，我们证明了PVS对sEF的影响是由血浆GFAP升高和白质疾病介导的。这些发现突出了成像和血浆生物标志物在当前针对痴呆的治疗领域中的潜在效用。
结论：血管周围间隙（PVS）和白质高信号（WMH）是小血管疾病的影像学标志。血浆胶质原纤维蛋白酸性蛋白（GFAP）是星形胶质损伤的生物标志物。PVS,WMH,和GFAP与神经变性的执行功能障碍有关。PVS对执行功能的影响由GFAP和白质疾病介导。
方法：在333名临床诊断为阿尔茨海默病/轻度认知障碍的参与者中，进行了调解分析，以评估神经影像学标志物与血浆生物标志物对sEF的关系。额颞叶痴呆,或来自安大略省神经退行性疾病研究倡议的脑血管疾病。
结果：PVS与sEF显着相关（c=-0.125±0.054，95％自举置信区间[CI][-0.2309，-0.0189]，p=0.021)。该效应由GFAP和WMH两者介导。
结论：在这个独特的神经退行性疾病临床队列中，我们证明了PVS对sEF的影响是由血浆GFAP升高和白质疾病介导的。这些发现突出了成像和血浆生物标志物在当前针对痴呆的治疗领域中的潜在效用。
结论：血管周围间隙（PVS）和白质高信号（WMH）是小血管疾病的影像学标志。血浆胶质原纤维蛋白酸性蛋白（GFAP）是星形胶质损伤的生物标志物。PVS,WMH,和GFAP与神经变性的执行功能障碍有关。PVS对执行功能的影响由GFAP和白质疾病介导。
