Department of Brain Sciences, Imperial College London, London, UK.
Department of Neurology, Peking University First Hospital, Beijing, China.
J Alzheimers Dis. 2024;100(3):973-986. doi: 10.3233/JAD-230442.
Neuroinflammation in Alzheimer's disease is known as an important process in the disease, yet how microglial activation affects disease progression remains unclear.
The current study aims to interrogate the predictive value of neuroinflammation biomarker (11C-PBR28 PET), together with A/T/N imaging markers on disease deterioration in a cognitively impaired patient cohort.
The study included 6 AD and 27 MCI patients, who had MRI, 11C-PBR28, 18F-flutemetamol (amyloid marker), 18F-AV1451 (tau marker) PET scans, and were followed up with multiple neuropsychological assessments for at least one year (1.6 and 2.8 years on average for AD and MCI). The predictive values of imaging biomarkers on baseline and longitudinal cognition were interrogated using linear regression to identify the biomarkers that could explain disease progression.
Linear mixed models found the average intercepts (baseline) MMSE were 23.5 for AD and 28.2 for MCI patients, and the slope of MMSE (annual change) were -0.74 for AD and -0.52 for MCI patients. White matter microstructural integrity was predictive of baseline cognition, while PET markers of amyloid, tau and neuroinflammation were predictive of longitudinal cognitive decline. Both amyloid and neuroinflammation PET markers were predictors independent of each other. And a sub-group analysis showed the predictive effect of neuroinflammation on cognitive decline is independent of amyloid and tau.
Our study highlights the prognostic value of disease specific markers (amyloid, tau and neuroinflammation) in clinically diagnosed AD and MCI patients and suggests that the effects of these molecular markers are mediated by structural damage to the brain.
阿尔茨海默病中的神经炎症是疾病的一个重要过程，但小胶质细胞激活如何影响疾病进展尚不清楚。
本研究旨在探讨神经炎症生物标志物（11C-PBR28 PET）与 A/T/N 成像标志物对认知障碍患者队列疾病恶化的预测价值。
该研究纳入了 6 名 AD 患者和 27 名 MCI 患者，他们接受了 MRI、11C-PBR28、18F-flutemetamol（淀粉样蛋白标志物）、18F-AV1451（tau 标志物）PET 扫描，并进行了多次神经心理学评估，至少随访一年（AD 和 MCI 的平均随访时间分别为 1.6 年和 2.8 年）。使用线性回归探讨了影像学生物标志物对基线和纵向认知的预测价值，以确定能够解释疾病进展的生物标志物。
线性混合模型发现 AD 患者的平均 MMSE 截距（基线）为 23.5，MCI 患者为 28.2，MMSE 的斜率（年变化）为 AD 患者为-0.74，MCI 患者为-0.52。白质微观结构完整性预测基线认知，而淀粉样蛋白、tau 和神经炎症的 PET 标志物预测纵向认知下降。淀粉样蛋白和神经炎症 PET 标志物都是独立的预测因素。亚组分析表明，神经炎症对认知下降的预测作用独立于淀粉样蛋白和 tau。
我们的研究强调了疾病特异性标志物（淀粉样蛋白、tau 和神经炎症）在临床诊断的 AD 和 MCI 患者中的预后价值，并表明这些分子标志物的作用是由大脑结构损伤介导的。
