From the Departments of Neurology (C.A.R., D.B.R., A.d.H., N.A.S., K.N.S., G.J.F.), Internal Medicine (T.M.G.), and Radiology (S.P.), Yale University School of Medicine; and Yale Center for Brain and Mind Health (C.A.R., A.d.H., S.P., K.N.S., G.J.F.), New Haven, CT.
Neurology. 2024 Jan 23;102(2):e208010. doi: 10.1212/WNL.0000000000208010. Epub 2023 Dec 20.
Poor oral health is a modifiable risk factor that is associated with clinically observed cardiovascular disease. However, the relationship between oral and brain health is not well understood. We tested the hypothesis that poor oral health is associated with worse neuroimaging brain health profiles in middle-aged persons without stroke or dementia.
We performed a 2-stage cross-sectional neuroimaging study using UK Biobank data. First, we tested for association between self-reported poor oral health and MRI neuroimaging markers of brain health. Second, we used Mendelian randomization (MR) analyses to test for association between genetically determined poor oral health and the same neuroimaging markers. Poor oral health was defined as the presence of dentures or loose teeth. As instruments for the MR analysis, we used 116 independent DNA sequence variants linked to increased composite risk of dentures or teeth that are decayed, missing, or filled. Neuroimaging markers of brain health included white matter hyperintensity (WMH) volume and aggregate measures of fractional anisotropy (FA) and mean diffusivity (MD), 2 metrics indicative of white matter tract disintegrity obtained through diffusion tensor imaging across 48 brain regions.
We included 40,175 persons (mean age 55 years, female sex 53%) enrolled from 2006 to 2010, who underwent a dedicated research brain MRI between 2014 and 2016. Among participants, 5,470 (14%) had poor oral health. Poor oral health was associated with a 9% increase in WMH volume (β = 0.09, SD = 0.014, < 0.001), 10% change in aggregate FA score (β = 0.10, SD = 0.013, < 0.001), and 5% change in aggregate MD score (β = 0.05, SD = 0.013, < 0.001). Genetically determined poor oral health was associated with a 30% increase in WMH volume (β = 0.30, SD = 0.06, < 0.001), 43% change in aggregate FA score (β = 0.43, SD = 0.06, < 0.001), and 10% change in aggregate MD score (β = 0.10, SD = 0.03, < 0.01).
Among middle age Britons without stroke or dementia, poor oral health was associated with worse neuroimaging brain health profiles. Genetic analyses confirmed these associations, supporting a potentially causal association. Because the neuroimaging markers evaluated in this study precede and are established risk factors of stroke and dementia, our results suggest that oral health, an easily modifiable process, may be a promising target for very early interventions focused on improving brain health.
口腔健康不良是一种可改变的风险因素,与临床观察到的心血管疾病有关。然而,口腔健康与大脑健康之间的关系尚未得到很好的理解。我们检验了这样一个假设,即口腔健康不良与中年人群中无中风或痴呆的神经影像学大脑健康状况较差有关。
我们使用英国生物库数据进行了 2 阶段横断面神经影像学研究。首先,我们检验了自我报告的口腔健康不良与 MRI 神经影像学脑健康指标之间的关联。其次,我们使用孟德尔随机化 (MR) 分析来检验遗传决定的口腔健康不良与相同神经影像学指标之间的关联。口腔健康不良定义为佩戴义齿或牙齿松动。作为 MR 分析的工具,我们使用了 116 个独立的 DNA 序列变异,这些变异与义齿或牙齿受损、缺失或填充的复合风险增加有关。大脑健康的神经影像学指标包括脑白质高信号(WMH)体积和各向异性分数(FA)和平均扩散系数(MD)的综合指标,这 2 个指标通过扩散张量成像获得,涵盖 48 个大脑区域。
我们纳入了 40175 名(平均年龄 55 岁,女性 53%)参与者,他们于 2006 年至 2010 年登记,并于 2014 年至 2016 年期间接受了专门的研究性脑 MRI。在参与者中,有 5470 人(14%)口腔健康不良。口腔健康不良与 WMH 体积增加 9%(β=0.09,SD=0.014,<0.001)、FA 综合评分变化 10%(β=0.10,SD=0.013,<0.001)和 MD 综合评分变化 5%(β=0.05,SD=0.013,<0.001)相关。遗传决定的口腔健康不良与 WMH 体积增加 30%(β=0.30,SD=0.06,<0.001)、FA 综合评分变化 43%(β=0.43,SD=0.06,<0.001)和 MD 综合评分变化 10%(β=0.10,SD=0.03,<0.01)相关。
在没有中风或痴呆的英国中年人群中,口腔健康不良与神经影像学大脑健康状况较差有关。遗传分析证实了这些关联,支持了潜在的因果关系。由于本研究评估的神经影像学标志物先于中风和痴呆的风险因素,并已确立为这些风险因素,因此我们的结果表明,口腔健康是一种易于改变的过程,可能是改善大脑健康的早期干预措施的一个有希望的目标。