MRC Integrative Epidemiology Unit at the University of Bristol, UK; School of Psychological Science, University of Bristol, 12a Priory Road, Bristol, UK; Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, UK.
MRC Integrative Epidemiology Unit at the University of Bristol, UK; School of Psychological Science, University of Bristol, 12a Priory Road, Bristol, UK; Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, UK; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Brain Behav Immun. 2023 May;110:30-42. doi: 10.1016/j.bbi.2023.02.010. Epub 2023 Feb 13.
Inflammation is associated with cognitive functioning and dementia in older adults, but whether inflammation is related to cognitive functioning in youth and whether these associations are causal remains unclear.
In a population-based cohort (Avon Longitudinal Study of Parents and Children; ALSPAC), we investigated cross-sectional associations of inflammatory markers (C-reactive protein [CRP], Interleukin-6 [IL-6] and Glycoprotein acetyls [GlycA]) with measures of cold (working memory, response inhibition) and hot (emotion recognition) cognition at age 24 (N = 3,305 in multiple imputation models). Furthermore, we conducted one-sample and two-sample bidirectional Mendelian randomization (MR) analyses to examine potential causal effects of genetically-proxied inflammatory markers (CRP, GlycA, IL-6, IL-6 receptor, soluble IL-6 receptor) on cognitive measures (above) and on general cognitive ability.
In the ALSPAC cohort, there was limited evidence of an association between standardised inflammatory markers and standardised cognitive measures at age 24 after adjusting for potential confounders (N = 3,305; beta range, -0.02 [95 % confidence interval (CI) -0.06 to 0.02, p = 0.27] to 0.02 [95 % CI -0.02 to 0.05, p = 0.33]). Similarly, we found limited evidence of potential effects of 1-unit increase in genetically-proxied inflammatory markers on standardised working memory, emotion recognition or response inhibition in one-sample MR using ALSPAC data (beta range, -0.73 [95 % CI -2.47 to 1.01, p = 0.41] to 0.21 [95 % CI -1.42 to 1.84, p = 0.80]; or on standardised general cognitive ability in two-sample MR using the latest Genome-Wide Association Study (GWAS) datasets (inverse-variance weighted beta range, -0.02 [95 % CI -0.05 to 0.01, p = 0.12] to 0.03 [95 % CI -0.01 to 0.07, p = 0.19]).
Our MR findings do not provide strong evidence of a potential causal effect of inflammatory markers (CRP, IL-6, IL-6 receptor, GlycA) on the cognitive functions examined here. Given the large confidence intervals in the one-sample MR, larger GWAS of specific cognitive measures are needed to enable well-powered MR analyses to investigate whether inflammation causally influences specific cognitive domains.
炎症与老年人的认知功能和痴呆有关，但炎症是否与年轻人的认知功能有关，以及这些关联是否具有因果关系尚不清楚。
在一项基于人群的队列研究（阿冯纵向研究父母和孩子；ALSPAC）中，我们调查了炎症标志物（C 反应蛋白[CRP]、白细胞介素 6[IL-6]和糖蛋白乙酰基[GlycA]）与 24 岁时冷（工作记忆、反应抑制）和热（情绪识别）认知的横断面关联（在多个插补模型中，N=3305）。此外，我们进行了单样本和双样本双向 Mendelian 随机化（MR）分析，以检查遗传上接近的炎症标志物（CRP、GlycA、IL-6、IL-6 受体、可溶性 IL-6 受体）对认知测量（上述）和一般认知能力的潜在因果影响。
在 ALSPAC 队列中，在校正潜在混杂因素后，标准化炎症标志物与 24 岁时的标准化认知测量之间的关联证据有限（N=3305；β范围，-0.02[95%置信区间（CI）-0.06 至 0.02，p=0.27]至 0.02[95%CI-0.02 至 0.05，p=0.33]）。同样，我们发现使用 ALSPAC 数据进行单样本 MR 时，遗传上接近的炎症标志物增加 1 个单位对标准化工作记忆、情绪识别或反应抑制的潜在影响证据有限（β范围，-0.73[95%CI-2.47 至 1.01，p=0.41]至 0.21[95%CI-1.42 至 1.84，p=0.80]）；或在使用最新全基因组关联研究（GWAS）数据集进行双样本 MR 时，对标准化一般认知能力的潜在影响（逆方差加权β范围，-0.02[95%CI-0.05 至 0.01，p=0.12]至 0.03[95%CI-0.01 至 0.07，p=0.19]）。
我们的 MR 研究结果并未提供炎症标志物（CRP、IL-6、IL-6 受体、GlycA）对我们在此处检查的认知功能具有潜在因果影响的有力证据。鉴于单样本 MR 的置信区间较大，需要进行更大规模的特定认知措施的 GWAS，以便能够进行具有足够效力的 MR 分析，以调查炎症是否会因果影响特定的认知领域。
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