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2026 Volume 48 Issue 7
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Su Mouxiao, Liao Bo, Chen Shasha, et al. Study on the correlationand mechanism between periodontitis and cerebral small vessel disease related cognitive impairment based on neuroimaging[J]. Journal of Southwest University Natural Science Edition, 2026, 48(7): 203-214. doi: 10.13718/j.cnki.xdzk.2026.07.016
Citation: Su Mouxiao, Liao Bo, Chen Shasha, et al. Study on the correlationand mechanism between periodontitis and cerebral small vessel disease related cognitive impairment based on neuroimaging[J]. Journal of Southwest University Natural Science Edition, 2026, 48(7): 203-214. doi: 10.13718/j.cnki.xdzk.2026.07.016
shu

Study on the correlationand mechanism between periodontitis and cerebral small vessel disease related cognitive impairment based on neuroimaging

  • 1.

    Department of Rehabilitation Medicine, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang Sichuan 621000, China

  • 2.

    Department of Neurology, Zigong First People's Hospital, Zigong Sichuan 643000, China

  • 3.

    Department of Neurology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang Sichuan 621000, China

  • 4.

    Department of Stomatology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang Sichuan 621000, China

More Information
  • Received Date: 27/12/2025
    Available Online: 20/07/2026

  • MSC: R743.9

  • To investigate the association between periodontitis and cerebral small vessel disease (CSVD) related cognitive impairment, as well as its neuroimaging characteristics, a total of 172 patients with CSVD who were admitted to Mianyang Central Hospital from May 2024 to February 2025 were enrolled. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), and patients were divided into the CSVD related cognitive impairment (CSVD-CI) group and the CSVD with normal cognition (CSVD-NC) group. All participants underwent brain magnetic resonance imaging and periodontal assessment. The neuroimaging characteristics and MoCA scores were compared among patients with different severities of periodontitis, and periodontal parameters were analyzed between the CSVD-CI and CSVD-NC groups. Multivariate logistic regression was conducted to evaluate the association between periodontitis and CSVD-CI. The results indicated that all CSVD patients had varying extents of periodontitis. Compared with the CSVD-NC group, the CSVD-CI group had a significantly higher prevalence of moderate-to-severe periodontitis and more severe dentition defect, and the differences were statistically significant (p < 0.05). Multivariate logistic regression analysis indicated that moderate-to-severe periodontitis was independently associated with both CSVD-CI and moderate-to-severe CSVD burden (p < 0.05). Moderate-to-severe periodontitis can exacerbate neuroimaging lesions of CSVD, thereby promoting the occurrence and development of CSVD-CI. These findings suggest that periodontal health management has potential clinical value in the prevention and treatment of CSVD and should be emphasized in the comprehensive management of CSVD patients.

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  • [1] Mok V C T, Cai Y, Markus H S. Vascular cognitive impairment and dementia: mechanisms, treatment, and future directions[J]. International Journal of Stroke, 2024, 19(8): 838-856. doi: 10.1177/17474930241279888

    CrossRef Google Scholar

    [2] 中华医学会老年医学分会老年神经病学组. 脑小血管病相关认知功能障碍中国诊疗指南(2019)[J]. 阿尔茨海默病及相关病, 2019, 38(4): 345-354.

    Google Scholar

    [3] Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges[J]. The Lancet Neurology, 2010, 9(7): 689-701. doi: 10.1016/S1474-4422(10)70104-6

    CrossRef Google Scholar

    [4] 中国卒中学会. 中国血管性认知障碍诊治指南(2024版)[J]. 中华医学杂志, 2024, 104(31): 2881-2894.

    Google Scholar

    [5] Wardlaw J M, Smith C, Dichgans M. Small vessel disease: mechanisms and clinical implications[J]. The Lancet Neurology, 2019, 18(7): 684-696. doi: 10.1016/S1474-4422(19)30079-1

    CrossRef Google Scholar

    [6] Low A, Mak E, Rowe J B, et al. Inflammation and cerebral small vessel disease: a systematic review[J]. Ageing Research Reviews, 2019, 53(11): 100916.

    Google Scholar

    [7] Evans L E, Taylor J L, Smith C J, et al. Cardiovascular comorbidities, inflammation, and cerebral small vessel disease[J]. Cardiovascular Research, 2021, 117(13): 2575-2588.

    Google Scholar

    [8] Sun H Y, Du M Q, Tai B J, et al. Prevalence and associated factors of periodontal conditions among 55- to 74-year-old adults in China: results from the 4th National Oral Health Survey[J]. Clinical Oral Investigations, 2020, 24(12): 4403-4412. doi: 10.1007/s00784-020-03306-4

    CrossRef Google Scholar

    [9] Nilsson H, Berglund J S, Renvert S. Periodontitis, tooth loss and cognitive functions among older adults[J]. Clinical Oral Investigations, 2018, 22(5): 2103-2109. doi: 10.1007/s00784-017-2307-8

    CrossRef Google Scholar

    [10] Hajishengallis G, Chavakis T. Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities[J]. Nature Reviews Immunology, 2021, 21(7): 426-440. doi: 10.1038/s41577-020-00488-6

    CrossRef Google Scholar

    [11] Lei S, Li J, Yu J J, et al. Porphyromonas gingivalis bacteremia increases the permeability of the blood-brain barrier via the Mfsd2a/Caveolin-1 mediated transcytosis pathway[J]. International Journal of Oral Science, 2023, 15(1): 3. doi: 10.1038/s41368-022-00215-y

    CrossRef Google Scholar

    [12] Mayer C, Walther C, Borof K, et al. Association between periodontal disease and microstructural brain alterations in the Hamburg City Health Study[J]. Journal of Clinical Periodontology, 2024, 51(12): 1598-1609. doi: 10.1111/jcpe.13828

    CrossRef Google Scholar

    [13] Adam H S, Lakshminarayan K, Wang W, et al. The prospective association between periodontal disease and brain imaging outcomes: the Atherosclerosis Risk in Communities study[J]. Journal of Clinical Periodontology, 2022, 49(4): 322-334. doi: 10.1111/jcpe.13586

    CrossRef Google Scholar

    [14] Demmer R T, Norby F L, Lakshminarayan K, et al. Periodontal disease and incident dementia: the Atherosclerosis Risk in Communities Study (ARIC)[J]. Neurology, 2020, 95(12): 1660-1671.

    Google Scholar

    [15] Ye N S, Deng B, Hu H, et al. The association between oral health and mild cognitive impairment in community-dwelling older adults[J]. Frontiers in Public Health, 2024, 12: 1464439. doi: 10.3389/fpubh.2024.1464439

    CrossRef Google Scholar

    [16] Deng Z X, Li J M, Zhang Y H, et al. No genetic causal associations between periodontitis and brain atrophy or cognitive impairment: evidence from a comprehensive bidirectional Mendelian randomization study[J]. BMC Oral Health, 2024, 24(1): 571. doi: 10.1186/s12903-024-04367-7

    CrossRef Google Scholar

    [17] Wardlaw J M, Smith E E, Biessels G J, et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration[J]. The Lancet Neurology, 2013, 12(8): 822-838. doi: 10.1016/S1474-4422(13)70124-8

    CrossRef Google Scholar

    [18] Fazekas F, Kleinert R, Offenbacher H, et al. Pathologic correlates of incidental MRI white matter signal hyperintensities[J]. Neurology, 1993, 43(9): 1683-1689. doi: 10.1212/WNL.43.9.1683

    CrossRef Google Scholar

    [19] Doubal F N, MacLullich A M J, Ferguson K J, et al. Enlarged perivascular spaces on MRI are a feature of cerebral small vessel disease[J]. Stroke, 2010, 41(3): 450-454. doi: 10.1161/STROKEAHA.109.564914

    CrossRef Google Scholar

    [20] Staals J, Makin S D J, Doubal F N, et al. Stroke subtype, vascular risk factors, and total MRI brain small-vessel disease burden[J]. Neurology, 2014, 83(14): 1228-1234. doi: 10.1212/WNL.0000000000000837

    CrossRef Google Scholar

    [21] Tonetti M S, Greenwell H, Kornman K S. Staging and grading of periodontitis: framework and proposal of a new classification and case definition[J]. Journal of Clinical Periodontology, 2018, 45(S20): S149-S161.

    Google Scholar

    [22] Löe H. The gingival index, the plaque index and the retention index systems[J]. The Journal of Periodontology, 1967, 38(6): 610-616. doi: 10.1902/jop.1967.38.6.610

    CrossRef Google Scholar

    [23] Turesky S, Gilmore N D, Glickman I. Modified quigley hein plaque index[J]. Journal of Periodontology, 1970, 41(10): 41-43.

    Google Scholar

    [24] Zhou L J, Lin W Z, Meng X Q, et al. Periodontitis exacerbates atherosclerosis through Fusobacterium nucleatum-promoted hepatic glycolysis and lipogenesis[J]. Cardiovascular Research, 2023, 119(8): 1706-1717. doi: 10.1093/cvr/cvad045

    CrossRef Google Scholar

    [25] Hansen P R, Holmstrup P. Cardiovascular diseases and periodontitis[M]//Periodontitis: Advances in Experimental Research. Cham: Springer, 2022: 261-280.

    Google Scholar

    [26] León-López M, Cabanillas-Balsera D, Martín-González J, et al. Atherosclerosis and chronic apical periodontitis: systematic review and meta-analysis[J]. Journal of Clinical Medicine, 2025, 14(5): 1504. doi: 10.3390/jcm14051504

    CrossRef Google Scholar

    [27] Gualtero D F, Lafaurie G I, Buitrago D M, et al. Oral microbiome mediated inflammation, a potential inductor of vascular diseases: a comprehensive review[J]. Frontiers in Cardiovascular Medicine, 2023, 10: 1250263. doi: 10.3389/fcvm.2023.1250263

    CrossRef Google Scholar

    [28] Xie H Y, Qin Z Y, Ling Z J, et al. Oral pathogen aggravates atherosclerosis by inducing smooth muscle cell apoptosis and repressing macrophage efferocytosis[J]. International Journal of Oral Science, 2023, 15: 26. doi: 10.1038/s41368-023-00232-5

    CrossRef Google Scholar

    [29] Li X, Kiprowska M, Kansara T, et al. Neuroinflammation: a distal consequence of periodontitis[J]. Journal of Dental Research, 2022, 101(12): 1441-1449. doi: 10.1177/00220345221102084

    CrossRef Google Scholar

    [30] Kouki M A, Pritchard A B, Alder J E, et al. Do periodontal pathogens or associated virulence factors have a deleterious effect on the blood-brain barrier, contributing to Alzheimer's disease?[J]. Journal of Alzheimer's Disease, 2022, 85(3): 957-973. doi: 10.3233/JAD-215103

    CrossRef Google Scholar

    [31] Hu H Y, Ou Y N, Shen X N, et al. White matter hyperintensities and risks of cognitive impairment and dementia: a systematic review and meta-analysis of 36 prospective studies[J]. Neuroscience & Biobehavioral Reviews, 2021, 120: 16-27.

    Google Scholar

    [32] Li A, Du M, Chen Y T, et al. Periodontitis and cognitive impairment in older adults: the mediating role of mitochondrial dysfunction[J]. Journal of Periodontology, 2022, 93(9): 1302-1313. doi: 10.1002/JPER.21-0620

    CrossRef Google Scholar

    [33] Said-Sadier N, Sayegh B, Farah R, et al. Association between periodontal disease and cognitive impairment in adults[J]. International Journal of Environmental Research and Public Health, 2023, 20(6): 4707. doi: 10.3390/ijerph20064707

    CrossRef Google Scholar

    [34] Zhuang J B, Zhang S F, Chen H W, et al. Evidence of microbiota-host dysbiosis between periodontitis and cerebral small vessel disease[J]. Oral Diseases, 2025, 31(1): 248-263. doi: 10.1111/odi.15041

    CrossRef Google Scholar

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Study on the correlationand mechanism between periodontitis and cerebral small vessel disease related cognitive impairment based on neuroimaging

  • Received Date: 27/12/2025
  • Available Online: 20/07/2026

Abstract: 

To investigate the association between periodontitis and cerebral small vessel disease (CSVD) related cognitive impairment, as well as its neuroimaging characteristics, a total of 172 patients with CSVD who were admitted to Mianyang Central Hospital from May 2024 to February 2025 were enrolled. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), and patients were divided into the CSVD related cognitive impairment (CSVD-CI) group and the CSVD with normal cognition (CSVD-NC) group. All participants underwent brain magnetic resonance imaging and periodontal assessment. The neuroimaging characteristics and MoCA scores were compared among patients with different severities of periodontitis, and periodontal parameters were analyzed between the CSVD-CI and CSVD-NC groups. Multivariate logistic regression was conducted to evaluate the association between periodontitis and CSVD-CI. The results indicated that all CSVD patients had varying extents of periodontitis. Compared with the CSVD-NC group, the CSVD-CI group had a significantly higher prevalence of moderate-to-severe periodontitis and more severe dentition defect, and the differences were statistically significant (p < 0.05). Multivariate logistic regression analysis indicated that moderate-to-severe periodontitis was independently associated with both CSVD-CI and moderate-to-severe CSVD burden (p < 0.05). Moderate-to-severe periodontitis can exacerbate neuroimaging lesions of CSVD, thereby promoting the occurrence and development of CSVD-CI. These findings suggest that periodontal health management has potential clinical value in the prevention and treatment of CSVD and should be emphasized in the comprehensive management of CSVD patients.

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  • 血管性认知障碍(Vascular Cognitive Impairment，VCI)是继阿尔茨海默病之后，我国60岁及以上人群认知障碍的第二大病因[1]。脑小血管病(Cerebral Small Vessel Disease，CSVD)是VCI的重要病因，其患病率随年龄增加而显著增加[2]。CSVD相关认知功能障碍(CSVD with Cognitive Impairment，CSVD-CI)约占VCI的35%~67%[3]，起病隐袭，从轻度认知障碍(Mild Cognitive Impairment，MCI)缓慢进展到痴呆，造成严重的社会和家庭负担，且目前尚缺乏有效治疗手段，故早期识别并干预尤为重要[4]。CSVD累及脑内小动脉、小动脉分支、毛细血管及小静脉，临床表现包括认知障碍、步态障碍和自主神经功能异常等，其典型影像学特征包括脑白质高信号(White Matter Hyperintensity，WMH)、腔隙、血管周围间隙(Perivascular Space，PVS)扩大及脑微出血(Cerebral Microbleed，CMB)等[5]。既往研究表明，全身性炎症与CSVD的严重程度及进展密切相关[6-7]。

    牙周炎是中老年人中最常见的口腔疾病之一，在我国人群中的患病率高达80%~90%[8]，其特征为牙周附着及牙槽骨逐渐破坏，伴慢性炎症[9]。牙周致病菌及其代谢产物可通过菌血症持续进入血液循环，诱发全身炎症，促进炎症介质释放，导致血管内皮功能障碍、氧化应激加剧及动脉粥样硬化，进而造成血脑屏障破坏及脑血流灌注障碍等[10-11]。目前，关于牙周炎与CSVD的因果关系尚无定论，已有临床研究结果也存在差异[12-13]。关于牙周炎与认知障碍相关性的系统综述和流行病学研究也未能得出一致结论[14-16]，尤其在牙周炎与CSVD-CI关联性方面，相关报道仍然有限，其潜在作用机制尚待阐明。基于此，本研究拟对CSVD患者的牙周临床指标、神经影像学特征及认知功能进行综合评估，探讨牙周炎严重程度与CSVD-CI患者神经影像负荷及认知障碍的相关性，从口腔健康管理角度为CSVD-CI的早期识别和干预提供新的思路。

1.   研究对象与方法

    1.1.   研究对象

  • 选择2024年5月至2025年2月在绵阳市中心医院就诊的172例CSVD患者作为研究对象。

    纳入标准：1) 年龄为50~80岁。2) 头颅磁共振成像(Magnetic Resonance Imaging，MRI)显示CSVD神经影像标志物[17]，符合以下任一情况：① WMH，Fazekas评分≥2；② WMH，Fazekas评分为1，且存在两种以上血管危险因素(包括高血压、高脂血症、糖尿病、肥胖、当前吸烟及既往除卒中以外的血管事件)；③ WMH，Fazekas评分为1，且伴有皮层下腔隙；④近期皮层下小梗死。

    排除标准：1) 扩散加权成像显示最大直径超过20 mm的急性缺血性梗死；2) 急性出血性脑卒中；3) 急性蛛网膜下腔出血、未治疗的脑血管畸形或未治疗的直径大于3 mm的颅内血管瘤；4) 神经退行性疾病，如阿尔茨海默病和帕金森病；5) 疑似非血管性起源的WMH，如多发性硬化症、脑白质营养不良和代谢性脑病；6) 根据《精神障碍诊断与统计手册》第5版标准确诊的精神障碍；7) 无法完成MRI检查；8) 严重器质性疾病，如恶性肿瘤，预期寿命少于5年；9) 不能配合完成认知测评及牙周检查者。

    本研究经绵阳市中心医院伦理委员会批准(批准号：S2020034)，受试者均自愿参加并签署知情同意书。按照研究统一标准化问卷收集CSVD患者的人口学信息(包括年龄、性别、受教育程度、目前吸烟或饮酒情况)以及既往病史(包括高血压、糖尿病、血脂异常、冠心病、卒中)。

    • 1.2.   MRI神经影像评估

  • 在西门子3.0T磁共振上完成图像采集，使用标准化头部线圈。扫描方案包括轴位T1加权，轴位T2加权、液体衰减反转恢复(Fluid-Attenuated Inversion Recovery，FLAIR)和弥散加权成像(Diffusion Weighted Imaging，DWI)、磁敏感加权成像(Susceptibility Weighted Imaging，SWI)。T1加权成像：采用三维磁化准备快速梯度回波序列，重复时间(Repetition Time，TR) 2 000 ms，回波间隔7 ms，回波时间(Echo Time，TE) 2.3 ms，反转时间450 ms，扫描视野240×240 mm2，矩阵256×256，激励次数1，层厚1 mm，无层间隔，偏转角12°。T2加权成像：采用三维快速自旋回波序列采集，TR 3 200 ms，TE 380 ms，扫描视野230×230 mm2，矩阵256×256，体素大小0.9×0.9×1.2 mm3，层厚1.2 mm，无层间隔。FLAIR序列：采用三维快速自旋回波序列进行采集，TR 5 000 ms，TE 380 ms，反转时间1 800 ms，翻转角120°，扫描视野230×230 mm2，矩阵256×256，体素大小0.9×0.9×1.2 mm3，层厚1.2 mm，无层间隔。DWI采用单次激发自旋回波-平面回波成像序列采集，TR 6 800 ms，TE 85 ms，扫描视野240×240 mm2，矩阵128×128，体素大小1.9×1.9×3.0 mm3，层厚3.0 mm，无层间隔。SWI采用三维流动补偿梯度回波序列，TR 35 ms，TE 20 ms，翻转角15°，扫描视野240×240 mm2，矩阵384×384，体素大小0.6×0.6×1.5 mm3，层厚1.5 mm，无层间隔。WMH定义为T2加权或FLAIR序列上脑白质区高信号区域，采用Fazekas视觉分级法对脑室周围WMH(Periventricular WMH，PWMH)和深部WMH(Deep WMH，DWMH)进行评分[18]。PWMH评分标准：0分为无病变；1分为帽状或者铅笔样薄层病变；2分为病变呈光滑的晕圆；3分为脑室旁白质高信号延伸至脑深部。DWMH评分标准：0分为无病变；1分为零星点状病变；2分为点状病变开始融合；3分为大片融合高信号。PWMH和DWMH评分之和即为WMH总分，总分分级：总分0分为Fazekas 0级，1~2分为Fazekas 1级，3~4分为Fazekas 2级，5~6分为Fazekas 3级。PVS定义为T2序列上直径小于3 mm的点状或线状高信号，PVS用半定量评分量表进行分级[19]。腔隙定义为FLAIR序列上直径3~20 mm的圆形或椭圆形脑脊液信号且周围环绕高信号。脑微出血(Cerebral Microbleed，CMB)在SWI序列上表现为直径2~10 mm的圆形低密度病变[17]，记录腔隙和脑微出血的总数。由经过统一培训的两位资深神经内科医师进行阅片评定，CSVD负荷计算：腔隙≥1个计1分、脑微出血灶≥1个计1分、基底节区中至重度PVS计1分、WMH(PWMH Fazekas 3级或DWMH Fazekas 2~3级)计1分，上述4项影像学标志物所得分值相加，即为CSVD总体负荷评分。根据此评分评价CSVD的严重程度，0~1分为轻度，2分为中度，3~4分为重度[20]。由两名对临床资料不知情的资深神经影像医生评估CSVD神经影像标志物，评估结果出现不一致情况时由另一名神经内科高级医生进行判定，对判定结果进行一致性评估。评估者之间可靠性由Kappa系数评价，结果显示：WMH的Fazekas评分为0.89，腔隙为0.82，脑微出血为0.80，PVS为0.922。

    • 1.3.   牙周指标评估

  • 根据2018年牙周病分类标准进行牙周炎诊断及严重程度分级(用临床附着水平(Clinical Attachment Level，CAL)表示，CAL 1~2 mm为轻度；CAL 3~4 mm为中度；CAL≥5 mm为重度)[21]。使用牙周探针探查6颗指数牙(16、21、24、36、41、44)的6个位点(唇/颊侧近中、正中和远中，舌/腭侧近中、正中和远中)，采用Löe[22]的标准记录相关牙周指数，对缺失牙数、探诊深度(Probing Depth，PD)、临床附着水平(CAL)及牙龈指数(Gingival Index，GI)进行评分。牙列缺损分为3类：简单牙列缺损(≤8颗牙齿的缺失)、复杂牙列缺损(＞8颗牙齿的缺失)以及完整牙列(无牙齿缺失)。PD具体指牙龈边缘至牙周袋底部的距离。CAL为从牙釉牙骨质交界处到牙龈沟或牙周袋底部的距离。GI半定量分级标准：0分为牙龈正常；1分为轻度牙龈水肿，但无出血；2分为牙龈水肿并伴有出血；3分为牙龈有自发性出血倾向或出现溃疡。依据Quigley-Hein菌斑指数(Plaque Index，PLI)的Turesky改良法[23]记录PLI，记录牙齿缺失数量，由同一名经过培训的牙周病专科医生完成患者牙周检查评估。

    • 1.4.   认知功能测评

  • 采用蒙特利尔认知评估量表(MoCA)进行认知功能评估，量表包括视空间、执行能力、记忆力、注意力、语言能力、抽象思维、计算力、定向力8个认知领域，总分为30分。受教育年限≤12年者总分加1分；MoCA分值≥26分为认知正常，＜26分为认知障碍。

    • 1.5.   统计学分析

  • 连续变量先进行正态性检验(Kolmogorov-Smirnov检验)。符合正态分布的数据以 x±s表示，两组间比较采用独立样本t检验，并进行方差齐性检验；不符合正态分布的数据以中位数(四分位数间距)表示，组间比较采用Mann-Whitney U检验。计数资料以频数表示，组间差异采用χ2检验，当理论频数小于5时采用Fisher精确检验。采用二元Logistic回归分析评估牙周炎程度与CSVD负荷及CSVD-CI的独立相关性，因变量为CSVD-CI状态(有/无)或CSVD负荷等级(轻度/中重度)，自变量为牙周炎严重程度(轻度/中重度)，协变量包括可能的混杂因素，如年龄、性别、受教育程度、高血压、糖尿病等。回归模型采用Enter法逐步纳入自变量，结果以优势比(Odds Ratio，OR)及95%置信区间(95%CI)表示。采用有序Logistic回归分析，探讨牙周炎病变程度与WMH分级的相关性。所有统计分析使用SPSS 22.0软件，采用双侧检验，p＜0.05为差异有统计学意义。

2.   结果与分析

    2.1.   纳入CSVD患者的基线资料

  • 共纳入CSVD患者172例，平均年龄为66.13±8.56岁，其中男性103例(59.88%)；MoCA评分为18.62±5.36，105例(61.05%)患者存在认知障碍。共有106例(61.63%)患者的CSVD总负荷为轻度。纳入CSVD患者均患有牙周炎，其中轻度牙周炎患者83例(48.26%)，中重度牙周炎患者89例(51.74%)，见表 1。

    • 2.2.   轻度与中重度牙周炎患者临床特征和CSVD神经影像特征比较

  • 轻度与中重度牙周炎患者在性别、高血压、糖尿病、吸烟情况及受教育程度方面差异无统计学意义(p＞0.05)。中重度牙周炎组的脑室周围及深部WMH分级均高于轻度牙周炎组(p＜0.05)，两组的腔隙病变及PVS程度差异无统计学意义(p＞0.05)。中重度牙周炎组的CSVD负荷较轻度牙周炎组更高(p=0.001)；轻度牙周炎组的MoCA评分(20.69±4.70)高于中重度牙周炎组(16.84±5.28)(p＜0.001)，结果见表 2。

    • 2.3.   CSVD-CI和CSVD-NC两组临床特征与牙周指标比较

  • CSVD-CI组患者年龄显著高于CSVD-NC组(p=0.003)，而两组在性别、吸烟情况及受教育程度方面差异无统计学意义(p＞0.05)。CSVD-CI组高血压、糖尿病及颈动脉粥样硬化的患病比例均高于CSVD-NC组(p＜0.05)。牙周指标比较显示，CSVD-CI组中重度牙周炎患者68例(64.76%)，显著高于CSVD-NC组的14例(20.90%，p＜0.001)，且牙列缺损程度更重。CSVD-CI组的PLI、GI及CAL均高于CSVD-NC组，差异有统计学意义(p＜0.01)。此外，PD超过6 mm位点数≥1个的患者在CSVD-CI组占51.43%，显著高于CSVD-NC组的28.36%(p=0.015)，结果见表 3。

    • 2.4.   牙周指标与CSVD总体负荷的相关性

  • 根据CSVD总体负荷评分，将研究对象分为轻度CSVD组和中重度CSVD组。比较结果显示，中重度CSVD组中重度牙周炎患者的患病率(66.67%)显著高于轻度CSVD组(42.45%)(p=0.001)，牙列缺损程度更重(p=0.015)。此外，中重度CSVD组的PLI、GI、PD超过6 mm位点数和CAL水平均显著高于轻度CSVD组，差异有统计学意义，结果见表 4。

    以中重度CSVD总体负荷为因变量进行二元Logistic回归分析，由表 5可知，未调整混杂因素时，中重度牙周炎与中重度CSVD独立相关(OR：2.923，95%CI：1.328~6.434，p=0.008)。在进一步纳入年龄、高血压和糖尿病等变量后，中重度牙周炎仍与中重度CSVD独立相关(OR：3.538，95%CI：1.526~8.202，p=0.003)，同时糖尿病亦与中重度CSVD独立相关(OR：3.295，95%CI：1.218~8.918，p=0.019)。由表 6可知，以WMH分级为因变量，调整牙周炎、年龄、高血压、糖尿病等变量，有序Logistic回归分析显示，中重度牙周炎是WMH严重程度更高的独立危险因素(OR：2.621，95%CI：1.197~5.743，p=0.016)。

    • 2.5.   牙周病变与CSVD-CI的相关性

  • 以CSVD-CI为因变量的二元Logistic回归分析显示(表 7)，未校正模型中，中重度牙周炎与CSVD-CI显著相关(OR：1.175，95%CI：1.100~1.254，p=0.001)。在调整年龄、高血压及糖尿病等潜在混杂因素后，结果仍显示中重度牙周炎为CSVD-CI的独立危险因素(OR：2.172，95%CI：1.172~4.027，p=0.014)。同时，糖尿病(OR：2.389，95%CI：1.212~4.708，p=0.012)及高血压(OR：1.072，95%CI：1.003~1.147，p=0.041)也与CSVD-CI独立相关，而年龄差异无统计学意义。调整PLI、GI、CAL、PD超过6 mm位点数共4项牙周指标后，结果显示CAL与CSVD-CI独立相关(OR：3.119，95%CI：1.669~5.829，p=0.001)。

3.   讨论与结论

    3.1.   讨论

  • 本研究系统分析了牙周炎病变与CSVD-CI以及CSVD神经影像特征负荷的相关性，结果显示，中重度牙周炎患者脑室旁和深部WMH负荷显著高于轻度牙周炎患者，CMB发生率也更高，而PVS和腔隙未见明显差异，CSVD总负荷在中重度牙周炎组显著增加。与CSVD-NC相比，CSVD-CI组患者牙周炎更为严重，伴随更重的牙列缺损，PLI、GI、CAL、PD等牙周指标均显著升高。多因素Logistic回归分析显示，中重度牙周炎不仅与CSVD总体负荷独立相关，同时也是CSVD-CI的危险因素。综合表明，牙周炎可能通过炎症及血管病理机制参与CSVD的发生发展，并与认知功能障碍密切相关。

    牙周炎作为一种由牙周致病菌及其产物驱动的慢性炎症状态，通过炎症介质、细菌组分以及免疫反应扩散至全身，与多系统疾病相关。既往研究显示，牙周炎可显著增加动脉粥样硬化、冠心病及脑卒中的风险[24-26]。牙周致病菌(如牙龈卟啉单胞菌)可进入血液循环并定植于血管内皮，诱导内皮功能障碍，促进黏附分子和趋化因子表达，增强炎性细胞浸润，继而推动动脉粥样硬化斑块的形成与发展[27]。此外，牙周致病菌诱导的平滑肌细胞凋亡及相关囊泡释放，可通过miRNA信号通路抑制巨噬细胞的清除功能，从而导致斑块坏死核心扩大与稳定性下降[28]。本研究发现中重度牙周炎患者颈动脉粥样硬化患病率显著高于轻度牙周炎患者(p=0.003)。鉴于动脉粥样硬化与CSVD存在共同的病理基础，即血管内皮功能障碍、慢性炎症及脑血流调节异常[5]，本研究发现牙周炎对CSVD的影响与其对动脉粥样硬化的作用一致：中重度牙周炎组CSVD总负荷显著高于轻度牙周炎组(p=0.001)。以中重度CSVD总负荷为因变量的Logistic回归分析显示，未调整混杂因素时，中重度牙周炎为其独立危险因素(OR：2.923，95%CI：1.328~6.434，p=0.008)，在调整年龄、高血压和糖尿病等变量后，中重度牙周炎仍是CSVD总负荷的独立危险因素(OR：3.538，95%CI：1.526~8.202，p=0.003)。牙周炎参与CSVD病理生理过程可能的机制主要包括：1) 牙周炎所致的全身慢性低水平炎症的介质(如IL-6、TNF-α、CRP)可进入血液循环，诱发系统性炎症反应，导致脑小血管内皮功能障碍和脑白质损伤[29]；2) 牙周致病菌及其毒性成分(如脂多糖)可通过血流及内皮细胞表面的Toll样受体激活炎症反应，同时诱导活性氧过量产生，导致一氧化氮生物利用度下降，损害血管舒张功能，并可进入脑血管或通过颅神经进入颅内，激活小胶质细胞，导致脑实质炎症反应、破坏血脑屏障[30]；3) 通过分子模拟，牙周致病菌诱发自身免疫反应造成脑微循环损伤[10]；4) 牙周炎影响全身代谢状态，并与炎症协同，加速内皮功能障碍的进程，促进血小板活化与高凝状态，加速动脉粥样硬化斑块进展并提高急性心脑血管事件风险[27]。WMH作为CSVD最主要的神经影像学标志之一，被认为是CSVD-CI的核心病理基础。WMH导致大脑白质纤维传导受损，影响执行功能和信息处理速度。WMH病变与脑小血管慢性缺血、髓鞘脱失及小胶质细胞炎症密切相关。有研究表明，全身性炎症在WMH形成和进展中起重要作用[31]。一项纳入2 030名受试者的横断面研究发现，仅调整年龄和性别，CAL、PD等牙周指标与WMH负荷显著相关，但进一步调整受教育水平及心血管危险因素后，上述相关性消失[12]。与之不同，本研究结果显示，以WMH分级为因变量，在控制年龄、高血压、糖尿病等混杂变量后，有序Logistic回归分析结果显示中重度牙周炎与WMH严重程度显著相关(OR：2.621，95%CI：1.197~5.743，p=0.016)，提示中重度牙周炎是WMH高负荷的风险因素。与之前研究结果存在差异的原因可能包括：1) 本研究对象均为确诊的CSVD患者，其中中重度牙周炎占比高(51.74%)；2) 研究人群心血管危险因素负担相对较低(高血压46.51%，糖尿病23.26%)；3) 研究样本中WMH总分2~3分比例较高，提示中重度牙周炎是WMH负荷的风险因素。因此，本研究认为，牙周炎可能通过炎症及血管损伤机制独立促进CSVD影像病变的进展，提示口腔健康管理在CSVD防治中的潜在价值，需大样本、前瞻性研究进一步验证。

    一项纳入1 883名超过60岁人群的横断面研究显示，Ⅲ/Ⅳ期牙周炎患者的认知能力显著低于Ⅰ/Ⅱ期患者，可能与线粒体功能障碍介导的机制有关[32]。有研究发现牙龈炎症、CAL、PD及牙槽骨丧失均与认知功能障碍相关，但其潜在机制尚未完全阐明[33]。本研究结果与上述研究一致，CSVD-CI组的中重度牙周炎患病率显著高于CSVD-NC组，且牙列缺损程度更重。进一步分析发现，CSVD-CI组的PLI、GI、CAL及PD超过6 mm位点比例均明显升高。PLI水平升高提示口腔卫生状况差，并与反映炎症活动度的PD增加呈正相关，提示CSVD患者应加强口腔清洁与牙周健康管理。CAL能够客观反映牙周组织的长期累积性损害，在调整PLI、GI及PD超过6 mm位点后，CAL与CSVD-CI显著相关。这与Zhuang等[34]研究结果一致，提示CAL作为牙周炎的核心指标，不仅能反映疾病的严重程度，还能在CSVD-CI中发挥关键作用，因此在CSVD-CI防治管理中应予以重视。本研究系统性分析了牙周炎与CSVD-CI的相关性，以CSVD-CI为因变量的二元Logistic回归分析显示，无论是否校正年龄、高血压及糖尿病等传统危险因素，中重度牙周炎均与CSVD-CI独立相关。该结果提示，牙周炎对CSVD-CI的影响可能独立于传统心脑血管危险因素。结合中重度牙周炎亦是CSVD总负荷独立危险因素这一发现，提示牙周炎可能通过加剧CSVD病变负荷在认知功能损害中的作用。

    • 3.2.   结论

  • 本研究系统地探讨了牙周炎与CSVD神经影像学负荷及CSVD-CI的相关性，发现中重度牙周炎为CSVD-CI的独立危险因素，其作用可能部分通过加重CSVD总负荷而介导。结果提示，牙周健康管理在CSVD防治中具有潜在的临床价值，应在患者综合管理中予以重视。本研究亦存在一定局限性：1) 研究设计为单中心横断面研究且样本量相对有限，可能存在选择偏倚，因果关系尚无法明确，需要开展多中心、大样本、前瞻性研究验证。2) 研究未做各亚认知域与牙周指数的相关性分析，有待后续进一步研究。

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