Clarke R, Smith A D, Jobst K A, Refsum H, Sutton L, Ueland P M
Clinical Trial Service Unit, Nuffield Department of Clinical Medicine, Oxford, England.
Arch Neurol. 1998 Nov;55(11):1449-55. doi: 10.1001/archneur.55.11.1449.
Recent studies suggest that vascular disease may contribute to the cause of Alzheimer disease (AD). Since elevated plasma total homocysteine (tHcy) level is a risk factor for vascular disease, it may also be relevant to AD.
To examine the association of AD with blood levels of tHcy, and its biological determinants folate and vitamin B12.
Case-control study of 164 patients, aged 55 years or older, with a clinical diagnosis of dementia of Alzheimer type (DAT), including 76 patients with histologically confirmed AD and 108 control subjects.
Referral population to a hospital clinic between July 1988 and April 1996.
Serum tHcy, folate, and vitamin B12 levels in patients and controls at entry; the odds ratio of DAT or confirmed AD with elevated tHcy or low vitamin levels; and the rate of disease progression in relation to tHcy levels at entry.
Serum tHcy levels were significantly higher and serum folate and vitamin B12 levels were lower in patients with DAT and patients with histologically confirmed AD than in controls. The odds ratio of confirmed AD associated with a tHcy level in the top third (> or = 14 micromol/L) compared with the bottom third (< or = 11 micromol/L) of the control distribution was 4.5 (95% confidence interval, 2.2-9.2), after adjustment for age, sex, social class, cigarette smoking, and apolipoprotein E epsilon4. The corresponding odds ratio for the lower third compared with the upper third of serum folate distribution was 3.3 (95% confidence interval, 1.8-6.3) and of vitamin B12 distribution was 4.3 (95% confidence interval, 2.1-8.8). The mean tHcy levels were unaltered by duration of symptoms before enrollment and were stable for several years afterward. In a 3-year follow-up of patients with DAT, radiological evidence of disease progression was greater among those with higher tHcy levels at entry.
Low blood levels of folate and vitamin B12, and elevated tHcy levels were associated with AD. The stability of tHcy levels over time and lack of relationship with duration of symptoms argue against these findings being a consequence of disease and warrant further studies to assess the clinical relevance of these associations for AD.
近期研究表明，血管疾病可能在阿尔茨海默病（AD）的病因中起作用。由于血浆总同型半胱氨酸（tHcy）水平升高是血管疾病的一个危险因素，它可能也与AD相关。
研究AD与血液中tHcy水平及其生物学决定因素叶酸和维生素B12之间的关联。
对164名55岁及以上临床诊断为阿尔茨海默型痴呆（DAT）的患者进行病例对照研究，其中包括76名经组织学确诊为AD的患者和108名对照者。
1988年7月至1996年4月转诊至医院门诊的人群。
患者和对照者入组时的血清tHcy、叶酸和维生素B12水平；tHcy升高或维生素水平降低的情况下DAT或确诊AD的比值比；以及与入组时tHcy水平相关的疾病进展率。
DAT患者和经组织学确诊为AD的患者血清tHcy水平显著高于对照组，血清叶酸和维生素B12水平低于对照组。在对年龄、性别、社会阶层、吸烟和载脂蛋白E ε4进行校正后，与对照组分布中最低三分之一（≤11μmol/L）相比，确诊AD与tHcy水平处于最高三分之一（≥14μmol/L）相关的比值比为4.5（95%置信区间，2.2 - 9.2）。血清叶酸分布中最低三分之一与最高三分之一相比的相应比值比为3.3（95%置信区间，1.8 - 6.3），维生素B12分布的相应比值比为4.3（95%置信区间，2.1 - 8.8）。入组前症状持续时间对平均tHcy水平无影响，且之后数年保持稳定。在对DAT患者进行的3年随访中，入组时tHcy水平较高的患者疾病进展的影像学证据更多。
血液中叶酸和维生素B12水平低以及tHcy水平升高与AD相关。tHcy水平随时间的稳定性以及与症状持续时间缺乏关联表明这些发现并非疾病的结果，有必要进一步研究以评估这些关联对AD的临床相关性。
