Abstract:
The glymphatic system is considered to play a pivotal role in the clearance of disease-causing proteins in neurodegenerative diseases. This study employed MR diffusion tensor imaging (DTI) to evaluate glymphatic system function and its correlation with brain amyloid accumulation levels measured using [11C]Pittsburgh compound-B (PiB) PET/MRI. Fifty-six patients with mild cognitive impairment and early Alzheimer\'s disease (AD: 70 ± 11 y) underwent [11C]PiB PET/MRI to assess amyloid deposition and were compared with 27 age-matched cognitively normal volunteers (CN: 69 ± 10y). All participants were evaluated for cognitive function using the Mini Mental State Examination (MMSE) before [11C]PiB PET/MRI. DTI images were acquired during the PET/MRI scan with several other MR sequences. The DTI analysis along the perivascular space index (DTI-ALPS index) was calculated to estimate the functional activity of the glymphatic system. Centiloid scale was applied to quantify amyloid deposition levels from [11C]PiB PET images. All patients in the AD group showed positive [11C]PiB accumulation, whereas all CN participants were negative. ALPS-index for all subjects linearly correlated with PiB centiloid, MMSE scores, and hippocampal volume. The correlation between the ALPS-index and PiB accumulation was more pronounced than with any other biomarkers. These findings suggest that glymphatic system dysfunction is a significant factor in the early stages of Alzheimer\'s disease.
摘要:
淋巴系统被认为在神经退行性疾病中的致病蛋白的清除中起关键作用。这项研究采用MR扩散张量成像(DTI)来评估淋巴系统功能及其与使用[11C]匹兹堡化合物B(PiB)PET/MRI测量的脑淀粉样蛋白积累水平的相关性。56例轻度认知障碍和早期阿尔茨海默病(AD:70±11y)患者接受[11C]PiBPET/MRI评估淀粉样蛋白沉积,并与27名年龄匹配的认知正常志愿者(CN:69±10y)进行比较。在[11C]PiBPET/MRI之前,使用迷你精神状态检查(MMSE)评估所有参与者的认知功能。DTI图像是在PET/MRI扫描期间与几个其他MR序列一起采集的。计算沿着血管周围空间指数(DTI-ALPS指数)的DTI分析以估计淋巴系统的功能活性。应用Centiloid量表来量化来自[11C]PiBPET图像的淀粉样蛋白沉积水平。AD组患者均显示[11C]PiB积累阳性,而所有CN参与者均为阴性。所有受试者的ALPS指数与PiBcentloid线性相关,MMSE分数,和海马体积。ALPS指数和PiB积累之间的相关性比任何其他生物标志物更明显。这些发现表明,淋巴系统功能障碍是阿尔茨海默病早期的重要因素。