Kantarci Kejal, Schwarz Christopher G, Reid Robert I, Przybelski Scott A, Lesnick Timothy G, Zuk Samantha M, Senjem Matthew L, Gunter Jeffrey L, Lowe Val, Machulda Mary M, Knopman David S, Petersen Ronald C, Jack Clifford R
Department of Radiology, Mayo Clinic, Rochester, Minnesota.
Department of Information Technology, Mayo Clinic, Rochester, Minnesota.
JAMA Neurol. 2014 Dec;71(12):1547-54. doi: 10.1001/jamaneurol.2014.1482.
Pathophysiologic mechanisms leading to loss of white matter integrity and the temporal positioning of biomarkers of white matter integrity relative to the biomarkers of gray matter neurodegeneration and amyloid load in the course of Alzheimer disease (AD) are poorly understood.
To investigate the effects of AD-related gray matter neurodegeneration and high β-amyloid on white matter microstructure in older adults without dementia.
DESIGN, SETTING, AND PARTICIPANTS: A population-based, longitudinal cohort study was conducted. Participants included in the Mayo Clinic Study of Aging (N = 701) who underwent magnetic resonance imaging, diffusion tensor imaging (DTI), and positron emission tomography studies with diagnoses of cognitively normal ([CN] n = 570) or mild cognitive impairment ([MCI] n = 131) were included. Both groups were divided into biomarker-negative, amyloid-positive-only, neurodegeneration-positive-only, and amyloid plus neurodegeneration-positive groups based on their amyloid load shown on carbon 11-labeled Pittsburgh Compound B positron emission tomography, AD hypometabolic pattern shown on fludeoxyglucose F 18 positron emission tomography, and/or hippocampal atrophy shown on magnetic resonance imaging.
Fractional anisotropy (FA) determined using DTI.
No FA alterations were observed in biomarker-negative MCI and amyloid-positive-only CN and MCI groups compared with biomarker-negative CN participants on voxel-based analysis (P < .05; familywise error corrected). Conversely, the neurodegeneration-positive-only and amyloid plus neurodegeneration-positive CN and MCI groups consistently had decreased FA in the fornix, which correlated with cognitive performance (ρ = 0.38; P < .001). Patients with MCI had more extensive white matter involvement than did those with CN, and the greatest FA decreases were observed in the amyloid plus neurodegeneration-positive MCI group (P < .05; familywise error corrected).
A high amyloid load does not influence diffusion tensor imaging-based measures of white matter integrity in the absence of coexistent gray matter neurodegeneration in older adults without dementia.
在阿尔茨海默病（AD）病程中，导致白质完整性丧失的病理生理机制以及白质完整性生物标志物相对于灰质神经退行性变和淀粉样蛋白负荷生物标志物的时间定位尚不清楚。
研究AD相关灰质神经退行性变和高β淀粉样蛋白对无痴呆老年人白质微观结构的影响。
设计、地点和参与者：进行了一项基于人群的纵向队列研究。纳入梅奥诊所衰老研究（N = 701）的参与者，他们接受了磁共振成像、扩散张量成像（DTI）和正电子发射断层扫描研究，诊断为认知正常（[CN]，n = 570）或轻度认知障碍（[MCI]，n = 131）。根据碳11标记的匹兹堡化合物B正电子发射断层扫描显示的淀粉样蛋白负荷、氟脱氧葡萄糖F 18正电子发射断层扫描显示的AD低代谢模式和/或磁共振成像显示的海马萎缩，将两组分为生物标志物阴性、仅淀粉样蛋白阳性、仅神经退行性变阳性以及淀粉样蛋白加神经退行性变阳性组。
使用DTI确定的分数各向异性（FA）。
基于体素分析，与生物标志物阴性的CN参与者相比，生物标志物阴性的MCI组以及仅淀粉样蛋白阳性的CN和MCI组未观察到FA改变（P <.05；家族性误差校正）。相反，仅神经退行性变阳性以及淀粉样蛋白加神经退行性变阳性的CN和MCI组穹窿的FA持续降低，这与认知表现相关（ρ = 0.38；P <.001）。MCI患者的白质受累比CN患者更广泛，并且在淀粉样蛋白加神经退行性变阳性的MCI组中观察到最大的FA降低（P <.05；家族性误差校正）。
在无痴呆的老年人中，在不存在共存灰质神经退行性变的情况下，高淀粉样蛋白负荷不会影响基于扩散张量成像的白质完整性测量。
