Wen Chun-Hsien, Kang Hong-Yo, Chan Julie Y H
Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan 33302, Taiwan.
Department of Anesthesiology, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan.
Int J Mol Sci. 2024 Nov 22;25(23):12575. doi: 10.3390/ijms252312575.
Considerable studies have demonstrated that osteoarthritis (OA) is a risk factor for dementia. The precise mechanisms underlying the association between OA and increased risk for cognitive dysfunction, however, remain unclear. This study aimed at exploring the associations between pro-inflammatory cytokines/chemokines, biomarkers of Alzheimer's disease (AD), pain intensity, and cognitive decline in knee joint OA patients. A total of 50 patients (26 in OA group and 24 in non-OA control group) were enrolled in this prospective, observational study. The visual analogue scale (VAS) score for pain intensity and Cognitive Abilities Screening Instrument (CASI) score for cognitive functions were examined in both groups. The plasma and cerebrospinal fluid (CSF) levels of pro-inflammatory molecules (IL-1β, IL-6, TNF-α, fractalkine, BDNF, MCP-1, and TGF-β), as well as biomarkers of AD (Aβ, Aβ, total-tau, and phospho-tau), were measured by multiplex immunoassay. Correlations among plasma or CSF biomarkers and questionnaire scores were assessed using Pearson's correlation coefficient and simple linear regressions. There were more patients in the OA group whose CASI cutoff percentiles were <P5 or at P5 than in the control group. VAS pain scores were negatively correlated with cognitive domains, including total score, short term memory, attention, mental manipulation, abstract thinking, and judgment, of the CASI score. VAS scores were positively correlated with fractalkine, Aβ, and Aβ in CSF of OA patients. The CSF levels of Aβ and Aβ in OA patients were negatively correlated with attention and abstract scores in CASI. The findings of this study suggest that knee OA is associated with poor cognitive performance, and this association is particularly pronounced in OA patients with chronic pain. Higher levels of brain AD biomarkers, such as Aβ and Aβ, may partially mediate this relationship.
大量研究表明,骨关节炎(OA)是痴呆症的一个危险因素。然而,OA与认知功能障碍风险增加之间关联的具体机制仍不清楚。本研究旨在探讨膝关节OA患者中促炎细胞因子/趋化因子、阿尔茨海默病(AD)生物标志物、疼痛强度与认知衰退之间的关联。本项前瞻性观察性研究共纳入50例患者(OA组26例,非OA对照组24例)。两组均检查了疼痛强度的视觉模拟量表(VAS)评分和认知功能的认知能力筛查工具(CASI)评分。通过多重免疫测定法测量促炎分子(IL-1β、IL-6、TNF-α、趋化因子、脑源性神经营养因子、MCP-1和TGF-β)的血浆和脑脊液(CSF)水平,以及AD的生物标志物(Aβ、Aβ、总tau蛋白和磷酸化tau蛋白)。使用Pearson相关系数和简单线性回归评估血浆或脑脊液生物标志物与问卷评分之间的相关性。OA组中CASI临界百分位数< P5或处于P5的患者比对照组更多。VAS疼痛评分与CASI评分的认知领域呈负相关,包括总分、短期记忆、注意力、心理操作、抽象思维和判断力。VAS评分与OA患者脑脊液中的趋化因子、Aβ和Aβ呈正相关。OA患者脑脊液中Aβ和Aβ的水平与CASI中的注意力和抽象评分呈负相关。本研究结果表明,膝关节OA与认知功能不佳有关,这种关联在伴有慢性疼痛的OA患者中尤为明显。较高水平的脑AD生物标志物,如Aβ和Aβ,可能部分介导了这种关系。