Tondo Giacomo, Aprile Davide, De Marchi Fabiola, Sarasso Barbara, Serra Paola, Borasio Giordana, Rojo Esther, Arenillas Juan Francisco, Comi Cristoforo
Neurology Unit, Department of Translational Medicine, Sant'Andrea Hospital, University of Piemonte Orientale, Corso Abbiate 21, 13100 Vercelli, Italy.
Centre for Dementia and Cognitive Disorders, Sant'Andrea Hospital, Corso Abbiate 21, 13100 Vercelli, Italy.
J Clin Med. 2023 Jun 27;12(13):4298. doi: 10.3390/jcm12134298.
Growing evidence suggests that neuroinflammation plays a critical role in the pathogenesis of neurodegenerative diseases. Peripheral markers of inflammation, including blood cell counts and their ratios, such as the neutrophil-to-lymphocyte ratio (NLR), have been reported as an easily accessible and reliable proxy of central nervous system inflammation. However, the role of peripheral inflammation in dementia and Mild Cognitive Impairment (MCI) still needs to be clarified. In the current study, we aimed to assess the prognostic role of the NLR and other peripheral markers of inflammation in a sample of 130 amnestic MCI, followed up for two to five years. The Mini-Mental state examination (MMSE) score at baseline and follow-up visits was used to assess global cognitive status at each visit and the degree of cognitive decline over time. Baseline peripheral markers of inflammation included blood cell counts and ratios, specifically the NLR, the platelet-to-lymphocyte ratio (PLR), the monocyte-to-lymphocyte ratio (MLR), and the systemic immune inflammation index (SII). After classifying subjects into CONVERTERS and non-CONVERTERS (respectively, patients converting to dementia and subjects showing stability at the last available follow-up), we compared peripheral markers of inflammation among groups ed correlated them with cognitive measures, testing the ability of significant factors to predict conversion to dementia. In our cohort, CONVERTERS showed lower baseline MMSE scores (-value = 0.004) than non-CONVERTERS. In addition, CONVERTERS had statistically elevated NLR (-value = 0.005), PLR (-value = 0.002), and SII levels (-value = 0.015), besides a lower number of lymphocytes (-value = 0.004) compared with non-CONVERTERS. In a logistic regression analysis, baseline MMSE scores and NLR predicted conversion to dementia. Tertiles analysis showed that MCI with the highest NLR values had a higher conversion risk. Our study supports the hypothesis that a dysregulation of peripheral inflammation involving both lymphocytes and neutrophils may play a role in the pathogenesis of dementia, even at the early stages of neurodegeneration, as in the MCI condition.
越来越多的证据表明，神经炎症在神经退行性疾病的发病机制中起关键作用。炎症的外周标志物，包括血细胞计数及其比率，如中性粒细胞与淋巴细胞比率（NLR），已被报道为中枢神经系统炎症的一种易于获取且可靠的替代指标。然而，外周炎症在痴呆和轻度认知障碍（MCI）中的作用仍有待阐明。在本研究中，我们旨在评估130例遗忘型MCI样本中NLR和其他外周炎症标志物的预后作用，随访时间为2至5年。在基线和随访时的简易精神状态检查（MMSE）评分用于评估每次就诊时的整体认知状态以及随时间的认知衰退程度。炎症的基线外周标志物包括血细胞计数和比率，具体为NLR、血小板与淋巴细胞比率（PLR）、单核细胞与淋巴细胞比率（MLR）以及全身免疫炎症指数（SII）。在将受试者分为病情转变者和非病情转变者（分别为转变为痴呆的患者和在最后一次可用随访时表现稳定的受试者）后，我们比较了两组之间的外周炎症标志物，并将它们与认知指标相关联，测试显著因素预测转变为痴呆的能力。在我们的队列中，病情转变者的基线MMSE评分（P值 = 0.004）低于非病情转变者。此外，与非病情转变者相比，病情转变者的NLR（P值 = 0.005）、PLR（P值 = 0.002）和SII水平（P值 = 0.015）在统计学上有所升高，而淋巴细胞数量较少（P值 = 0.004）。在逻辑回归分析中，基线MMSE评分和NLR预测了转变为痴呆的情况。三分位数分析表明，NLR值最高的MCI转变风险更高。我们的研究支持这样一种假设，即涉及淋巴细胞和中性粒细胞的外周炎症失调可能在痴呆的发病机制中起作用，即使在神经退行性变的早期阶段，如在MCI情况下。
