Aging Research Center, Karolinska Institute, Stockholm, Sweden.
Department of Neurology, Ulm University Hospital, Ulm, Germany.
JAMA Psychiatry. 2019 Nov 1;76(11):1198-1205. doi: 10.1001/jamapsychiatry.2019.1694.
Impairment of methylation status (ie, methionine to homocysteine ratio) may be a modifiable risk factor for structural brain changes and incident dementia.
To investigate the association of serum markers of methylation status and sulfur amino acids with risk of incident dementia, Alzheimer disease (AD), and the rate of total brain tissue volume loss during 6 years.
DESIGN, SETTING, AND PARTICIPANTS: This population-based longitudinal study was performed from March 21, 2001, to October 10, 2010, in a sample of 2570 individuals aged 60 to 102 years from the Swedish Study on Aging and Care in Kungsholmen who were dementia free at baseline and underwent comprehensive examinations and structural brain magnetic resonance imaging (MRI) on 2 to 3 occasions during 6 years. Data analysis was performed from March 1, 2018, to October 1, 2018.
Incident dementia, AD, and the rate of total brain volume loss.
This study included 2570 individuals (mean [SD] age, 73.1 [10.4] years; 1331 [56.5%] female). The methionine to homocysteine ratio was higher in individuals who consumed vitamin supplements (median, 1.9; interquartile range [IQR], 1.5-2.6) compared with those who did not (median, 1.8; IQR, 1.3-2.3; P < .001) and increased per each quartile increase of vitamin B12 or folate. In the multiadjusted model, an elevated baseline serum total homocysteine level was associated with an increased risk of dementia and AD during 6 years: for the highest homocysteine quartile compared with the lowest, the hazard ratios (HRs) were 1.60 (95% CI, 1.01-2.55) for dementia and 2.33 (95% CI, 1.26-4.30) for AD. In contrast, elevated concentrations of methionine were associated with a decreased risk of dementia (HR, 0.54; 95% CI, 0.36-0.81) for the highest quartile compared with the lowest. Higher values of the methionine to homocysteine ratio were significantly associated with lower risk of dementia and AD: for the fourth methionine-homocysteine quartile compared with the first quartile, the HR was 0.44 (95% CI, 0.27-0.71) for incident dementia and 0.43 (95% CI, 0.23-0.80) for AD. In the multiadjusted linear mixed models, a higher methionine to homocysteine ratio was associated with a decreased rate of total brain tissue volume loss during the study period (β [SE] per 1-SD increase, 0.038 [0.014]; P = .007).
The methionine to homocysteine status was associated with dementia development and structural brain changes during the 6-year study period, suggesting that a higher methionine to homocysteine ratio may be important in reducing the rate of brain atrophy and decreasing the risk of dementia in older adults.
甲基化状态的损害（即蛋氨酸到同型半胱氨酸的比例）可能是结构脑变化和痴呆发病的可改变风险因素。
研究血清甲基化状态和含硫氨基酸标志物与痴呆、阿尔茨海默病（AD）发病风险以及 6 年内总脑组织体积损失率之间的关系。
设计、地点和参与者：这是一项基于人群的纵向研究，于 2001 年 3 月 21 日至 2010 年 10 月 10 日进行，样本来自瑞典 Kungsholmen 衰老和护理研究的 2570 名年龄在 60 至 102 岁之间、基线时无痴呆且在 6 年内进行了 2 至 3 次全面检查和结构脑磁共振成像（MRI）的个体。数据分析于 2018 年 3 月 1 日至 2018 年 10 月 1 日进行。
痴呆、AD 和总脑容量损失率的发生率。
本研究纳入了 2570 名个体（平均[标准差]年龄，73.1[10.4]岁；1331[56.5%]为女性）。与未服用维生素补充剂的个体相比（中位数 1.9；四分位距[IQR] 1.5-2.6），服用维生素补充剂的个体的蛋氨酸到同型半胱氨酸比值更高（中位数 1.8；IQR 1.3-2.3；P < .001），且每增加一个四分位的维生素 B12 或叶酸，比值都会升高。在多调整模型中，基线时血清总同型半胱氨酸水平升高与 6 年内痴呆和 AD 的发病风险增加相关：与最低四分位数相比，最高四分位数的风险比（HRs）分别为 1.60（95%CI 1.01-2.55）和 2.33（95%CI 1.26-4.30）。相反，同型半胱氨酸浓度升高与痴呆发病风险降低相关（HR，0.54；95%CI 0.36-0.81），与最低四分位数相比，最高四分位数的 HR 为 0.54。较高的蛋氨酸到同型半胱氨酸比值与痴呆和 AD 发病风险降低显著相关：与第一四分位数相比，第四四分位数的 HR 分别为 0.44（95%CI 0.27-0.71）和 0.43（95%CI 0.23-0.80）。在多调整线性混合模型中，蛋氨酸到同型半胱氨酸比值升高与研究期间总脑组织体积损失率降低相关（每增加 1-SD，β[SE]为 0.038[0.014]；P = .007）。
蛋氨酸到同型半胱氨酸状态与痴呆发病和 6 年研究期间的结构脑变化相关，这表明较高的蛋氨酸到同型半胱氨酸比值可能对降低大脑萎缩速度和降低老年人痴呆风险具有重要意义。
