BACKGROUND Osteopontin (OPN) is a proinflammatory cytokine that has been recently implicated in neuroinflammation and neurodegeneration. We hypothesized that an increase in plasma osteopontin is a deleterious neuroinflammatory marker in people with dementia and cerebral small vessel disease (CSVD). METHODS A pilot study was conducted on participants in the Northern Manhattan Study (NOMAS). Three groups were selected based on their dementia status and evidence of subclinical CSVD and chosen to be similar in age, sex, and education attainment: No dementia/No CSVD (n=19), Dementia/No CSVD (n=22), and Dementia+CSVD (n=21). Dementia (any type) was diagnosed by consensus adjudication following a series of comprehensive neuropsychological assessments and a review of the medical history. CSVD was indicated by silent brain infarcts, enlarged perivascular spaces, cerebral microbleeds, and white matter hyperintensity volumes (WMHV) on MRI. Multinomial logistic regression was used to examine the difference in OPN levels across groups, adjusting for key determinants of CSVD and neurodegeneration. RESULTS Plasma osteopontin levels were elevated in the Dementia+CSVD group (mean=70.69±39.00 ng/ml) but not in the Dementia/No CSVD group (mean=45.46±19.11 ng/ml) compared to the No dementia/No CSVD group (mean=36.43±15.72 ng/ml). Osteopontin was associated with Dementia+CSVD (Odds Ratio (OR) per ng/ml=1.06, 95%CI 1.02-1.11) after adjusting for covariates, including brain volume. OPN was strongly correlated with WMHV (Spearman's rank correlation =0.46, p=0.0001), but not with other components of CSVD. CONCLUSION In this pilot, greater levels of plasma osteopontin were associated with dementia with evidence of CSVD. This link was predominately driven by the contribution of OPN to dementia through the burden of white matter lesions.

中文翻译：

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骨桥蛋白与存在脑小血管疾病的痴呆有关。

背景骨桥蛋白（OPN）是一种促炎细胞因子，最近被认为与神经炎症和神经变性有关。我们假设血浆骨桥蛋白的增加是痴呆和脑小血管疾病 (CSVD) 患者的一种有害的神经炎症标志物。方法 对北曼哈顿研究 (NOMAS) 的参与者进行了一项试点研究。根据痴呆状况和亚临床 CSVD 证据选择三组，并选择年龄、性别和教育程度相似的组：无痴呆/无 CSVD (n=19)、痴呆/无 CSVD (n=22) 和痴呆+脑小血管病（n=21）。痴呆症（任何类型）是在一系列全面的神经心理学评估和病史回顾后通过共识裁决诊断出来的。CSVD 表现为无症状脑梗塞、血管周围间隙扩大、脑微出血和 MRI 上白质高信号体积 (WMHV)。使用多项逻辑回归来检查各组 OPN 水平的差异，并调整 CSVD 和神经退行性变的关键决定因素。结果 与无痴呆/无 CSVD 组相比，痴呆+CSVD 组的血浆骨桥蛋白水平升高（平均值=70.69±39.00 ng/ml），但痴呆/无 CSVD 组则没有升高（平均值=45.46±19.11 ng/ml） （平均值=36.43±15.72 ng/ml）。调整协变量（包括脑体积）后，骨桥蛋白与痴呆+脑小血管病相关（每 ng/ml 的优势比 (OR) = 1.06，95% CI 1.02-1.11）。OPN 与 WMHV 密切相关（Spearman 等级相关性 =0.46，p=0.0001），但与 CSVD 的其他组成部分无关。结论 在该试验中，较高水平的血浆骨桥蛋白与有脑小血管病证据的痴呆症相关。这种联系主要是由于 OPN 通过白质病变负担而导致痴呆。