Seshadri Sudha, Wolf Philip A, Beiser Alexa S, Selhub Jacob, Au Rhoda, Jacques Paul F, Yoshita Mitsuhiro, Rosenberg Irwin H, D'Agostino Ralph B, DeCarli Charles
Department of Neurology, School of Medicine, Boston University, Boston, Massachusetts 02118-2526, USA.
Arch Neurol. 2008 May;65(5):642-9. doi: 10.1001/archneur.65.5.642.
Elevated plasma total homocysteine (tHcy) levels have been associated with increased risk of dementia and stroke, but it is uncertain whether the mediating mechanisms are predominantly cellular, vascular, or both.
To evaluate the relationship between tHcy levels and findings at brain magnetic resonance imaging (MRI) in a community-based sample.
Our sample comprised 1965 participants in the Framingham Offspring Study (1050 women; mean [SD] age, 62 [9] years) who were free of clinical stroke, dementia, or other neurologic disease affecting brain MRI and for whom at least 1 measurement of plasma tHcy level (1991-2001) and a brain MRI (1999-2002) were available. We used multivariate regression analysis to relate initial (1991-1995) and concurrent (1998-2001) plasma tHcy levels to total cerebral brain volume and lobar volumes as measures of neuronal loss and atrophy and to the presence or absence of silent brain infarcts and extensive white matter hyperintensity (log-white matter intensity > or =1 SD above the age-adjusted mean) as separate measures of vascular injury.
Mean total cerebral brain volume was 78%. At MRI, 218 participants had silent brain infarcts and 250 demonstrated extensive white matter hyperintensity. Participants with a plasma tHcy level in the highest age- (-0.37%, P = .01) or sex-specific (-0.48%, P < .001) quartile had smaller total cerebral brain volumes compared with participants with lower tHcy levels. Initial tHcy levels were associated with a higher prevalence of silent brain infarct (relative risk, 1.5; 95% confidence interval, 1.1-2.1; P = .02) and concurrent tHcy levels, with smaller frontal (-0.14%, P = .001) and temporal lobar (-0.10%, P = .04) volumes. Prevalence of extensive white matter hyperintensity did not differ according to initial or concurrent plasma tHcy levels (relative risk, both 1.0; 95% confidence interval, 0.7-1.4 and 0.8-1.4, respectively).
Higher plasma tHcy levels are associated with smaller brain volume and the presence of silent brain infarcts at MRI, even in healthy, middle-aged adults. Thus, both cellular and vascular mechanisms may underlie the association of plasma tHcy level with brain aging, as reflected by the effects on both subclinical and overt disease.
血浆总同型半胱氨酸（tHcy）水平升高与痴呆和中风风险增加有关，但介导机制主要是细胞性、血管性还是两者兼而有之尚不确定。
在一个基于社区的样本中评估tHcy水平与脑磁共振成像（MRI）结果之间的关系。
我们的样本包括弗雷明汉后代研究中的1965名参与者（1050名女性；平均[标准差]年龄，62[9]岁），这些参与者无临床中风、痴呆或其他影响脑MRI的神经系统疾病，且至少有一次血浆tHcy水平测量值（1991 - 2001年）和一次脑MRI（1999 - 2002年）。我们使用多变量回归分析将初始（1991 - 1995年）和同期（1998 - 2001年）血浆tHcy水平与全脑总体积和脑叶体积相关联，以作为神经元丢失和萎缩的指标，并与无症状脑梗死和广泛白质高信号（对数白质强度高于年龄校正平均值1个标准差或更高）的存在与否相关联，作为血管损伤的单独指标。
平均全脑总体积为78%。在MRI检查中，218名参与者有无症状脑梗死，250名有广泛白质高信号。与tHcy水平较低的参与者相比，血浆tHcy水平处于最高年龄特异性（-0.37%，P = 0.01）或性别特异性（-0.48%，P < 0.001）四分位数的参与者全脑总体积较小。初始tHcy水平与无症状脑梗死的较高患病率相关（相对风险，1.5；95%置信区间，1.1 - 2.1；P = 0.02），同期tHcy水平与额叶（-0.14%，P = 0.001）和颞叶（-0.10%，P = 0.04）体积较小相关。广泛白质高信号的患病率根据初始或同期血浆tHcy水平无差异（相对风险，均为1.0；95%置信区间，分别为0.7 - 1.4和0.8 - 1.4）。
即使在健康的中年成年人中，较高的血浆tHcy水平也与较小的脑体积和MRI检查中无症状脑梗死的存在相关。因此，细胞和血管机制可能都构成了血浆tHcy水平与脑老化之间关联的基础，这体现在对亚临床和显性疾病的影响上。
