■慢性炎症被认为是阿尔茨海默病(AD)的重要组成部分,然而它与认知能力下降的关系,性别差异,和年龄不是很清楚。这项研究调查了炎症标志物之间的关系,认知,性别,轻度认知障碍(MCI)和AD患者的年龄。
■进行了系统评价,以确定病例对照研究,这些研究测量了血清中的认知功能和炎症标志物,等离子体,与健康对照(HC)参与者相比,MCI或AD患者的脑脊液。使用随机效应模型中计算的Hedges\'g进行荟萃分析。使用年龄,性别,和迷你精神状态检查(MMSE)值。
■共有106项没有高偏倚风险的研究纳入荟萃分析,包括18,145名个体:5625名AD参与者,3907名MCI参与者,和8613名HC参与者。联合血清和血浆荟萃分析发现,IL1β、IL6,IL8,IL18,CRP,与HC相比,AD患者的hsCRP显着升高。在CSF中,与HC相比,YKL40和MCP-1在AD中升高。与HC相比,MCI中的YKL40也升高。Meta回归分析突出了几个新发现:在AD中,MMSE与IL6呈负相关,与IL1α呈正相关。而在MCI研究中,MMSE与IL8和TNFα呈负相关。Meta回归还显示了IL1α水平的性别差异,IL4,IL6,IL18,hsCRP,MCP-1和YKL-40在AD和MCI研究中,发现年龄是CRP异质性的原因,MCI和AD中的MCP-1和IL4。
■IL6和YKL40水平升高可能反映MCI和AD中的小胶质细胞炎症活性。全身性炎症可能与中枢神经系统相互作用,AD和MCI患者认知功能低下与血清和血浆促炎细胞因子IL6和TNFα水平升高相关。此外,男性和女性之间的全身性炎症变化可能受到性别特异性激素变化的调节,例如在整个更年期过渡期间,女性的雌激素水平下降。需要对一系列生物样本类型进行纵向研究,以阐明MCI和AD患者炎症与认知之间关系的细微差别。了解全身和中枢炎症对认知功能的影响。
UNASSIGNED: Chronic inflammation is recognised as an important component of Alzheimer\'s disease (AD), yet its relationship with cognitive decline, sex-differences, and age is not well understood. This study investigated the relationship between inflammatory markers, cognition, sex, and age in individuals with mild cognitive impairment (MCI) and AD.
UNASSIGNED: A systematic review was performed to identify case-control studies which measured cognitive function and inflammatory markers in serum, plasma, and cerebrospinal fluid in individuals with MCI or AD compared with healthy control (HC) participants. Meta-analysis was performed with Hedges\' g calculated in a random effects model. Meta-regression was conducted using age, sex, and mini-mental status exam (MMSE) values.
UNASSIGNED: A total of 106 studies without a high risk of bias were included in the meta-analysis including 18,145 individuals: 5625 AD participants, 3907 MCI participants, and 8613 HC participants. Combined serum and plasma meta-analysis found that IL1β, IL6, IL8, IL18, CRP, and hsCRP were significantly raised in individuals with AD compared to HC. In CSF, YKL40, and MCP-1 were raised in AD compared to HC. YKL40 was also raised in MCI compared to HC. Meta-regression analysis highlighted several novel findings: MMSE was negatively correlated with IL6 and positively correlated with IL1α in AD, while in MCI studies, MMSE was negatively correlated with IL8 and TNFα. Meta-regression also revealed sex-specific differences in levels of IL1α, IL4, IL6, IL18, hsCRP, MCP-1, and YKL-40 across AD and MCI studies, and age was found to account for heterogeneity of CRP, MCP-1, and IL4 in MCI and AD.
UNASSIGNED: Elevated levels of IL6 and YKL40 may reflect microglial inflammatory activity in both MCI and AD. Systemic inflammation may interact with the central nervous system, as poor cognitive function in individuals with AD and MCI was associated with higher levels of serum and plasma proinflammatory cytokines IL6 and TNFα. Moreover, variations of systemic inflammation between males and females may be modulated by sex-specific hormonal changes, such as declining oestrogen levels in females throughout the menopause transition. Longitudinal studies sampling a range of biospecimen types are needed to elucidate the nuances of the relationship between inflammation and cognition in individuals with MCI and AD, and understand how systemic and central inflammation differentially impact cognitive function.