L'Heureux Joanna E, Corbett Anne, Ballard Clive, Vauzour David, Creese Byron, Winyard Paul G, Jones Andrew M, Vanhatalo Anni
Faculty of Health and Life Sciences, University of Exeter Medical School, University of Exeter, St Luke's campus, Exeter EX1 2LU, United Kingdom.
Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, United Kingdom.
PNAS Nexus. 2025 Jan 28;4(1):pgae543. doi: 10.1093/pnasnexus/pgae543. eCollection 2025 Jan.
Apolipoprotein () genotype and nitric oxide (NO) deficiency are risk factors for age-associated cognitive decline. The oral microbiome plays a critical role in maintaining NO bioavailability during aging. The aim of this study was to assess interactions between the oral microbiome, NO biomarkers, and cognitive function in 60 participants with mild cognitive impairment (MCI) and 60 healthy controls using weighted gene co-occurrence network analysis and to compare the oral microbiomes between carriers and noncarriers in a subgroup of 35 MCI participants. Within the MCI group, a high relative abundance of was associated with better indices of cognition relating to executive function (Switching Stroop, = 0.33, = 0.03) and visual attention (Trail Making, = -0.30, = 0.05), and in the healthy group, correlated with working memory (Digit Span, = 0.26, = 0.04). High abundances of ( = 0.38, = 0.01) and ( = 0.32, = 0.03), that co-occurred with correlated with better scores on executive function (Switching Stroop) in the MCI group. There were no differences in oral nitrate ( = 0.48) or nitrite concentrations ( = 0.84) between the MCI and healthy groups. Linear discriminant analysis Effect Size identified as a predictor for MCI and as a predictor of -carrier status. The principal findings of this study were that a greater prevalence of oral is linked to elevated genetic risk for dementia ( genotype) in individuals with MCI prior to dementia diagnosis and that interventions that promote the oral and suppress -dominated modules have potential for delaying cognitive decline.
载脂蛋白E（ApoE）基因型和一氧化氮（NO）缺乏是与年龄相关的认知衰退的风险因素。口腔微生物群在衰老过程中维持NO生物利用度方面起着关键作用。本研究的目的是使用加权基因共现网络分析评估60名轻度认知障碍（MCI）参与者和60名健康对照者的口腔微生物群、NO生物标志物和认知功能之间的相互作用，并在35名MCI参与者的亚组中比较ApoE携带者和非携带者的口腔微生物群。在MCI组中，较高的ApoE相对丰度与执行功能（转换斯特鲁普，r = 0.33，P = 0.03）和视觉注意力（连线测验，r = -0.30，P = 0.05）相关的更好认知指标有关，在健康组中，ApoE与工作记忆（数字广度，r = 0.26，P = 0.04）相关。在MCI组中，与ApoE共现的较高丰度的嗜黏蛋白阿克曼菌（r = 0.38，P = 0.01）和迟缓埃格特菌（r = 0.32，P = 0.03）与执行功能（转换斯特鲁普）的更好得分相关。MCI组和健康组之间的口腔硝酸盐（P = 0.48）或亚硝酸盐浓度（P = 0.84）没有差异。线性判别分析效应大小确定嗜黏蛋白阿克曼菌是MCI的预测因子，而迟缓埃格特菌是ApoE携带者状态的预测因子。本研究的主要发现是，在痴呆诊断前的MCI个体中，口腔ApoE的较高患病率与痴呆的遗传风险升高（ApoE基因型）有关，并且促进口腔嗜黏蛋白阿克曼菌和抑制ApoE主导模块的干预措施有可能延缓认知衰退。
