Hara J, Shankle W R, Barrentine L W, Curole M V
Junko Hara, Ph.D. Shankle Clinic, 3900 W Coast Hwy, Ste 310, Newport Beach, CA 92663, Phone: +1-949-478-8858 ex222, Fax: +1-949-242-2465, Email:
J Nutr Health Aging. 2016;20(8):825-834. doi: 10.1007/s12603-016-0688-z.
Studies have produced conflicting results assessing hyperhomocysteinemia (HYH) treatment with B vitamins in patients with normal cognition, Alzheimer's disease and related disorders (ADRD). This study examined the effect of HYH management with L-methylfolate (LMF), methylcobalamin (MeCbl; B12), and N-acetyl-cysteine (CFLN: Cerefolin®/Cerefolin-NAC®) on cognitive decline.
Prospective, case-control study of subjects followed longitudinally.
Outpatient clinic for cognitive disorders.
116 ADRD patients (34 with HYH, 82 with No-HYH) met inclusion and exclusion criteria to participate. No study participant took B vitamins.
HYH patients received CFLN, and No-HYH patients did not.
Cognitive outcome measures included MCI Screen (memory), CERAD Drawings (constructional praxis), Ishihara Number Naming (object recognition), Trails A and B (executive function), and F-A-S test (verbal fluency). Dependent or predictor measures included demographics, functional severity, CFLN and no CFLN treatment duration, ADRD diagnosis, memantine and cholinesterase inhibitor treatment. Linear mixed effects models with covariate adjustment were used to evaluate rate of change on cognitive outcomes.
The duration of CFLN treatment, compared to an equivalent duration without CFLN treatment, significantly slowed decline in learning and memory, constructional praxis, and visual-spatial executive function (Trails B). CFLN treatment slowed cognitive decline significantly more for patients with milder baseline severity. CFLN treatment effect increased as baseline functional severity decreased. The analytical model showed that treatment duration must exceed some minimum period of at least one year to slow the rate of cognitive decline.
After covariate adjustment, HYH+CFLN significantly slowed cognitive decline compared to No-HYH+No-CFLN. Longer CFLN treatment duration, milder baseline severity, and magnitude of homocysteine reduction from baseline were all significant predictors. There are a number of factors that could account for disagreement with other clinical trials of B vitamin treatment of HYH. Moreover, CFLN is chemically distinct from commonly used B vitamins as both LMF and MeCbl are the fully reduced and bioactive functional forms; CLFN also contains the glutathione precursor, N-acetyl-cysteine. The findings of other B vitamin trials of HYH can, therefore, only partly account for treatment effects of CFLN. These findings warrant further evaluation with a randomized, placebo-controlled trial.
在认知正常、患有阿尔茨海默病及相关疾病（ADRD）的患者中，关于使用B族维生素治疗高同型半胱氨酸血症（HYH）的研究结果相互矛盾。本研究探讨了使用L-甲基叶酸（LMF）、甲钴胺（MeCbl；维生素B12）和N-乙酰半胱氨酸（CFLN：Cerefolin®/Cerefolin-NAC®）管理HYH对认知衰退的影响。
对受试者进行纵向随访的前瞻性病例对照研究。
认知障碍门诊。
116例ADRD患者（34例患有HYH，82例未患HYH）符合纳入和排除标准并参与研究。没有研究参与者服用B族维生素。
HYH患者接受CFLN治疗，未患HYH的患者不接受治疗。
认知结果测量包括MCI筛查（记忆）、CERAD绘图（构建实践）、石原数字命名（物体识别）、A和B连线测验（执行功能）以及F-A-S测试（语言流畅性）。相关或预测指标包括人口统计学特征、功能严重程度、CFLN治疗和未进行CFLN治疗的持续时间、ADRD诊断、美金刚和胆碱酯酶抑制剂治疗。使用带有协变量调整的线性混合效应模型来评估认知结果的变化率。
与未进行CFLN治疗的同等持续时间相比，CFLN治疗的持续时间显著减缓了学习和记忆、构建实践以及视觉空间执行功能（B连线测验）的衰退。对于基线严重程度较轻的患者，CFLN治疗显著减缓了认知衰退。随着基线功能严重程度的降低，CFLN治疗效果增强。分析模型表明，治疗持续时间必须超过至少一年的某个最短期限才能减缓认知衰退率。
经过协变量调整后，与未患HYH+未接受CFLN治疗相比，患HYH+CFLN治疗显著减缓了认知衰退。CFLN治疗持续时间更长、基线严重程度较轻以及同型半胱氨酸从基线降低的幅度都是显著的预测因素。有许多因素可能导致与其他关于B族维生素治疗HYH的临床试验结果不一致。此外，CFLN在化学性质上与常用的B族维生素不同，因为LMF和MeCbl都是完全还原的生物活性功能形式；CLFN还含有谷胱甘肽前体N-乙酰半胱氨酸。因此，其他关于HYH的B族维生素试验结果只能部分解释CFLN的治疗效果。这些发现值得通过随机、安慰剂对照试验进行进一步评估。
