Increased Total Homocysteine Levels Predict the Risk of Incident Dementia Independent of Cerebral Small-Vessel Diseases and Vascular Risk Factors
Increased Total Homocysteine Levels Predict the Risk of Incident Dementia Independent of Cerebral Small-Vessel Diseases and Vascular Risk Factors
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DOI：
10.3233/jad-150458
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发表时间：
2016-01-01
影响因子：
4
通讯作者：
Kitagawa, Kazuo
中科院分区：
文献类型：
--
作者：
Miwa, Kaori;Tanaka, Makiko;Kitagawa, Kazuo
背景：同型半胱氨酸已被确定为卒中、脑血管疾病（SVD）和痴呆的潜在危险因素。目的：本研究旨在探讨同型半胱氨酸水平对痴呆发病的预测价值，同时控制MRI表现和血管危险因素。方法：在一项观察性研究中，在一组有血管危险因素的日本参与者中，我们评估了基线总同型半胱氨酸（tHcy）水平（每1 μ mol/L和tHcy的百分比）、基线mri发现的患病率和全因痴呆发生率之间的关系。基线脑MRI用于确定SVD（腔隙、白质高信号和脑微出血[CMBs]）和脑萎缩（内侧颞叶萎缩和双核比值）。使用逻辑回归分析来估计tHcy与每个MRI结果之间的横断面关联。采用Cox比例风险分析来估计tHcy和痴呆之间的纵向关联。结果：在643名受试者（年龄：67.2 +/- 8.4岁，男性：59%，受教育程度：12.9 +/- 2.6年）中，调整了几个潜在混杂因素（包括肾小球滤过率（eGFR）和内膜-中膜厚度）的多变量分析显示，最高的tHcy水平与腔隙、CMBs和严格深部CMBs相关。在平均7.3年的随访期间（范围：2-13年），47例患者被诊断为痴呆（阿尔茨海默病24例，血管性痴呆18例，混合型3例，其他2例）。在调整了年龄、性别、APOE ε 4、教育程度、BMI、MMSE、高血压、脑血管事件、eGFR和mri结果后，全因痴呆的tHcy水平（危险比[HR]: 1.08, p = 0.043）和tHcy最高分位数（风险比：2.50,p = 0.047）仍然显著。结论：我们的研究结果提供了额外的证据，证明tHcy有助于增加对痴呆风险的易感性。
Background: Homocysteine has been identified as a potential risk factor for stroke, cerebral small-vessel diseases (SVD), and dementia.Objective: The present study aimed to investigate the predictive value of homocysteine levels on incident dementia while simultaneously controlling for MRI findings and vascular risk factors.Methods: Within a Japanese cohort of participants with vascular risk factors in an observational study, we evaluated the association between baseline total homocysteine (tHcy) levels (per 1 mu mol/L and the tertile of tHcy), the prevalence of MRI-findings at baseline, and incident all-cause dementia. Baseline brain MRI was used to determine SVD (lacunas, white matter hyperintensities, and cerebral microbleeds [CMBs]) and atrophy (medial-temporal lobe atrophy and bicaudate ratio). Logistic regression analyses were used to estimate the cross-sectional association between tHcy and each of MRI findings. Cox proportional hazards analyses were performed to estimate the longitudinal association between tHcy and dementia.Results: In the 643 subjects (age: 67.2 +/- 8.4 years, male: 59%; education: 12.9 +/- 2.6 years), multivariable analyses adjusted for several potential confounders, including estimated glomerular filtration rate (eGFR) and intima-media thickness, showed that highest tHcy tertile was associated with lacunas, CMBs, and strictly deep CMBs. During the mean 7.3-year follow-up (range: 2-13), 47 patients were diagnosed with dementia (Alzheimer's disease: 24; vascular dementia: 18; mixed-type: 3; other: 2). After adjusting for age, gender, APOE epsilon 4, education, BMI, MMSE, hypertension, cerebrovascular events, eGFR, and MRI-findings, tHcy level (hazard ratios [HR]: 1.08, p = 0.043) and the highest tertile of tHcy (HR: 2.50, p = 0.047) for all-cause dementia remained significant.Conclusions: Our results provide additional evidence of tHcy that contributes to increased susceptibility to dementia risk.