Gussekloo J, Heijmans B T, Slagboom P E, Lagaay A M, Knook D L, Westendorp R G
Section of Gerontology and Geriatrics, Department of General Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
J Neurol Neurosurg Psychiatry. 1999 Oct;67(4):535-8. doi: 10.1136/jnnp.67.4.535.
Previous reports have shown raised plasma concentrations of homocysteine in older persons with cognitive impairment. This may be caused by environmental and genetic factors. The relation between cognitive function and a common ala/val mutation in the methylenetetrahydrofolate reductase (MTHFR) gene was studied in those over 85. Homozygous carriers of this mutation are characterised by a lifelong exposure to moderately raised plasma concentrations of homocysteine.
In the Leiden 85-plus Study, a population based study of persons aged 85 years and over, the score on the mini mental state examination (MMSE) and the presence of dementia dependent on the MTHFR genotypes were compared in 641 participants (456 women, 185 men) at baseline. In addition, the association between the MTHFR genotype and cognitive decline was studied by re-examining cognitive function of 172 participants without dementia at baseline after a median follow up of 4.0 years.
At baseline, carriers of the ala/ala genotype had a median MMSE score of 27 points (interquartile range (IQR) 21.5-29), for the ala/val genotype it was 26 points (IQR 20-29), and for the val/val genotype it was 27 points (IQR 20-28.3) (p=0.3). The prevalence of dementia was also not significantly different for the various genotypes (ala/ala 22%, ala/val 28%, val/val 27%; p=0.4). None of the carriers of the val/val genotype without cognitive impairment at baseline developed dementia during the follow up.
Although previous studies have shown that older persons with cognitive impairment have raised plasma concentrations of homocysteine, homozygosity for the ala to val mutation in the MTHFR gene is not a genetic risk factor for cognitive impairment in persons aged 85 years and over.
既往报告显示，认知功能受损的老年人血浆同型半胱氨酸浓度升高。这可能由环境和遗传因素引起。对85岁以上人群中认知功能与亚甲基四氢叶酸还原酶（MTHFR）基因常见的ala/val突变之间的关系进行了研究。该突变的纯合子携带者的特征是终生暴露于中度升高的血浆同型半胱氨酸浓度。
在莱顿85岁及以上研究中，这是一项针对85岁及以上人群的基于人群的研究，在基线时比较了641名参与者（456名女性，185名男性）的简易精神状态检查（MMSE）得分以及依赖于MTHFR基因型的痴呆症患病情况。此外，在中位随访4.0年后，通过重新检查172名基线时无痴呆症的参与者的认知功能，研究了MTHFR基因型与认知衰退之间的关联。
在基线时，ala/ala基因型携带者的MMSE得分中位数为27分（四分位间距（IQR）21.5 - 29），ala/val基因型为26分（IQR 20 - 29），val/val基因型为27分（IQR 20 - 28.3）（p = 0.3）。不同基因型的痴呆症患病率也无显著差异（ala/ala 22%，ala/val 28%，val/val 27%；p = 0.4）。基线时无认知障碍的val/val基因型携带者在随访期间均未发生痴呆症。
尽管既往研究表明认知功能受损的老年人血浆同型半胱氨酸浓度升高，但MTHFR基因ala至val突变的纯合性并非85岁及以上人群认知功能受损的遗传危险因素。
