同型半胱氨酸与脑萎缩：新加坡研究中的痴呆症流行病学。

Homocysteine and Cerebral Atrophy: The Epidemiology of Dementia in Singapore Study.

机构信息

Memory Ageing and Cognition Center (MACC), National University Health System, Singapore.

Raffles Neuroscience Center, Raffles Hospital, Singapore.

出版信息

J Alzheimers Dis. 2018;62(2):877-885. doi: 10.3233/JAD-170796.

DOI:10.3233/JAD-170796

PMID:29480177

Abstract

BACKGROUND

Plasma homocysteine levels are increasingly studied as a potential risk factor for dementia. Elevated homocysteine levels have been linked with gray and white matter volume reduction among individuals with mild cognitive impairment and Alzheimer's disease. However, the effects of homocysteine on brain changes in preclinical stages of dementia remain unexplored.

OBJECTIVE

To examine the association of elevated homocysteine levels with markers of neurodegeneration, i.e., white and gray matter volume in an elderly population.

METHODS

The study included 768 participants (mean age: 69.6±6.5 years, 51.3% women) from the Epidemiology of Dementia In Singapore study. Participants underwent a brain MRI scan and blood tests. Serum homocysteine was measured using competitive immunoassay. Cortical thickness and subcortical structural volume were quantified using FreeSurfer whereas white matter volume was quantified using a previous validated method.

RESULTS

Higher homocysteine levels were significantly associated with decreased global white matter volume [mean difference (β) in volume (ml) per micromole per liter (μmol/l) increase in homocysteine levels: - 0.555, 95% Confidence Interval (CI): - 0.873; - 0.237], decreased parietal cortical thickness [β in thickness (μm) per μmol/l increase in homocysteine levels:- 1.429, 95% CI: - 2.781; - 0.077], and smaller volumes of the thalamus [β: - 0.017, 95% CI: - 0.026; - 0.008], brainstem [β: - 0.037, 95% CI: - 0.058; - 0.016], and accumbens [β: - 0.004, 95% CI: - 0.006; - 0.002].

CONCLUSION

Higher homocysteine levels were associated with cerebral atrophy. Further studies are required to assess whether lowering plasma homocysteine levels may prevent neurodegenerative changes or delay progression of clinical symptoms before the development of dementia.

摘要

背景

血浆同型半胱氨酸水平作为痴呆的潜在危险因素，越来越受到研究关注。同型半胱氨酸水平升高与轻度认知障碍和阿尔茨海默病患者的灰质和白质体积减少有关。然而，同型半胱氨酸对痴呆临床前阶段脑变化的影响仍不清楚。

目的

研究在老年人群中，同型半胱氨酸水平升高与神经退行性变标志物（即白质和灰质体积）的相关性。

方法

这项研究纳入了来自新加坡痴呆症流行病学研究的 768 名参与者（平均年龄：69.6±6.5 岁，51.3%为女性）。参与者接受了脑部 MRI 扫描和血液检查。使用竞争免疫分析法测量血清同型半胱氨酸。使用 FreeSurfer 定量皮质厚度和皮质下结构体积，使用先前验证的方法定量白质体积。

结果

同型半胱氨酸水平升高与全脑白质体积减少显著相关[每增加 1 微摩尔每升（μmol/l）同型半胱氨酸水平，体积（ml）的平均差异（β）：-0.555，95%置信区间（CI）：-0.873；-0.237]，与顶叶皮质厚度变薄[每增加 1μmol/l 同型半胱氨酸水平，厚度（μm）的平均差异（β）：-1.429，95%CI：-2.781；-0.077]，以及丘脑[β：-0.017，95%CI：-0.026；-0.008]、脑干[β：-0.037，95%CI：-0.058；-0.016]和伏隔核[β：-0.004，95%CI：-0.006；-0.002]体积减小相关。